Usefulness of Stereotactic Radiotherapy Using CyberKnife for Recurrent Lymph Node Metastasis of Differentiated Thyroid Cancer.

A woman in her 60s presented with a recurrent lymph node metastasis from a papillary thyroid carcinoma in the right parapharyngeal space. She had already undergone total thyroidectomy, five resections for cervical lymph node metastases, and right carotid rebuilding. Surgical resection of the current metastasis was impossible. 131I-radioiodine therapy (RIT) with 3.7 GBq 131I was not effective; therefore, stereotactic radiation therapy (SRT) using a CyberKnife radiotherapy system was scheduled. The prescription dose was 21 Gy, and a dose covering 95% of the planning target volume (PTV) in three fractions was administered. The PTV was 4,790 mm3. Follow-up magnetic resonance imaging conducted 3 and 12 months after the SRT demonstrated a remarkable and gradual reduction of the recurrent lymph node metastasis in the right parapharyngeal space and no evidence of recurrence. For multidisciplinary therapy of unresectable and/or RIT unresponsive locoregional lymph node metastases and recurrences of DTC, SRT using the CyberKnife system should be considered.

Results of radiation monotherapy for primary central nervous system lymphoma in the 1990s.

PURPOSE: Results of radiation therapy for primary central nervous system lymphoma (PCNSL) were poor in the 1970-1980s, with most reported 5-year survival rates being less than 10%. To investigate whether the prognosis of PCNSL patients treated by radiation alone remains still poor, we investigated the results of radiation monotherapy in the 1990s. METHODS AND MATERIALS: We collected data on 132 patients with histologically proven PCNSL treated by radiation alone in the 1990s from three nationwide or regional multiinstitutional studies conducted by the Japanese Society for Therapeutic Radiology and Oncology (JASTRO) Lymphoma Study Group or the Chubu Radiation Oncology Group. Follow-up data were updated as far as possible. Eleven patients who did not complete planned radiotherapy were included. The data were analyzed in relation to patient and tumor characteristics. The median patient age was 63 years, and the World Health Organization performance status (PS) was 3 or 4 in 40% of the patients. Multiple tumors were seen in 34%. Whole-brain irradiation with or without focal boost was used in 92%. The median radiation dose to the tumor site was 50 Gy (range, 8-74 Gy). RESULTS: For all 132 patients, the median survival time was 18 months and the 5-year survival rate was 18.0%. For 62 patients with PS 0-3 and aged 16-65 years (i.e., those eligible for the European Organization for Research and Treatment of Cancer 20962 study), the median survival was 26 months and 5-year survival was 24%. The 5-year survival was 25% for patients 63 years old or younger, and 9.8% for those older than 63 years (p = 0.0005). The 5-year survival was 22% for patients with PS 0-2 and 13% for those with PS 3 or 4 (p = 0.0040). Multivariate analysis confirmed the negative influence of higher age on patient prognosis. CONCLUSIONS: The results of radiation monotherapy for PCNSL appear to have improved as compared with those reported previously. The results of new treatment should be evaluated in light of this finding. Since most prospective studies on the combined treatment exclude poor PS and high-age patients, the 5-year survival rate of 30% may not be regarded as a marked improvement over radiation alone.

Human papilloma virus (HPV) DNA associated with prognosis of cervical cancer after radiotherapy.

PURPOSE: The importance of human papilloma virus (HPV) infection in the outcome of cervical cancer after radiotherapy remains unknown. Our study explored whether the HPV status of tumors is associated with the outcome of radiotherapy in patients with cervical cancer. METHODS AND MATERIALS: A total of 84 patients with cervical cancer (6 Stage I, 10 Stage II, 49 Stage III, and 19 Stage IV) who underwent definitive radiotherapy between January 1995 and June 2000 were included in this study. Tumor samples were obtained from all patients by punch biopsy before radiotherapy. The presence of HPV and its type were analyzed by polymerase chain reaction (PCR) based assay using the consensus primers for E6 and L1 regions. Actuarial methods were used to calculate overall survival and disease-free survival. RESULTS: A total of 42 patients (50%) had cancer recurrence after radiotherapy. HPV-positive tumors were found in 76.2% (64 cases) of patients. HPV-negative patients survived for significantly shorter time periods compared to the HPV-positive patients in the overall survival (p = 0.007) and the disease-free survival (p = 0.005). According to multivariate analysis, HPV status is a significant predictor of both overall (p = 0.02) and disease-free survival time (p = 0.005). CONCLUSION: The results of this study suggest that HPV-negative patients with cervical carcinoma have a significantly poorer prognosis after radiotherapy, and HPV status may be used as a marker to optimize the treatment of patients with this type of cancer.

Prediction of outcome of advanced cervical cancer to thermoradiotherapy according to expression profiles of 35 genes selected by cDNA microarray analysis.

PURPOSE: To identify a set of genes related to thermoradiosensitivity of cervical carcinoma and to establish a predictive method. METHODS AND MATERIALS: A total of 19 patients with cervical cancer (1 with Stage IIIA, 11 with Stage IIIB, 5 with Stage IVA, and 2 with Stage IVB) who underwent definitive thermoradiotherapy between May 1995 and August 2001 were included in this study. We compared the expression profiles of 8 thermoradiosensitive and 11 thermoradioresistant tumors obtained by punch biopsy before treatment using a cDNA microarray consisting of 23,040 human genes. RESULTS: We selected 35 genes on the basis of a clustering analysis and confirmed the validity of these genes with a cross-validation test. Some of these genes were already known to be associated with apoptosis (BIK, TEGT, SSI-3), hypoxia-inducible genes (HIF1A, CA12), and tumor cell invasion and metastasis (CTSL, CTSB, PLAU, CD44). We developed a "predictive score" system that could clearly separate the thermoradiosensitive group from the thermoradioresistant group. CONCLUSION: These results from the treatment program between May 1995 and August 2001 showed that by using gene-expression profiles we can predict the outcome of thermoradiotherapy for advanced cervical carcinoma. A "predictive score" system was developed that could clearly separate the thermoradiosensitive group from the thermoradioresistant group. These results may eventually lead to the achievement of "personalized therapy" for this disease.

Primary central nervous system lymphoma in Japan 1995-1999: changes from the preceding 10 years.

PURPOSE: Previously, we conducted a nationwide survey of primary central nervous system lymphoma (PCNSL) treated between 1985 and 1994 in Japan. In the present study, we conducted further investigations of PCNSL patients treated between 1995 and 1999 to clarify possible changes with time in the clinical features, treatment, and outcome of this disease. METHODS: Thirteen Japanese institutions were surveyed, and data on 101 patients with histologically-confirmed PCNSL were collected. These data were compared with those of 167 patients treated at the same institutions between 1985 and 1994. RESULTS: Regarding patient and tumor characteristics, the proportion of patients with good performance status (PS) was significantly higher in the group treated during 1995-1999 than in that treated during 1985-1994, but other characteristics were not significantly different. Regarding treatment, more patients in the more recent period (66%) received systemic chemotherapy than those in the preceding period (53%, P = 0.049). For all patients, including those who did not complete radiotherapy, the median survival time was 17 months and 30 months in patients treated between 1985 and 1994 and those treated between 1995 and 1999, respectively, and the 5-year survival rate was 15% versus 31% (P = 0.0003). In both patient groups, higher age and tumor multiplicity were associated with poor prognosis in multivariate analysis. In patients treated between 1995 and 1999, those who received systemic chemotherapy showed significantly better prognosis than those who did not (P = 0.0049), but the difference was not significant in multivariate analysis (P = 0.23). CONCLUSIONS: The high survival rates observed in the present survey are comparable with those of recent prospective studies employing intensive chemoradiotherapy. The improvement in prognosis appeared to result, at least in part, from the increase in the proportion of patients with better PS. Since the clinical feature and treatment outcome of patients with PCNSL can thus change with the era, historical control data should not be used in comparing different treatment modalities.

A case of metastatic bone tumor of missed lung cancer showing unusual manifestations on chest radiogram.

We encountered a patient who had a primary unknown carcinoma with lumbago caused by lumbar vertebral metastasis as the initial chief complaint. Autopsy revealed primary pulmonary adenocarcinoma. Abnormal findings noted on plain chest radiogram and chest CT led to misdiagnosis as inflammatory changes. The primary lesion was poorly differentiated pulmonary adenocarcinoma that could not be diagnosed correctly using the diagnostic criteria of these diagnostic modalities.

Stenting of the superior mesenteric artery as a preoperative treatment for total pancreatectomy.

The patient was 58-year-old male with mucinous cyst adenocarcinoma of the pancreas. Prior to total pancreatectomy, preoperative CT and angiography showed a high-grade arteriosclerotic stenosis of about 1.0 cm in length in the ostium of the superior mesenteric artery (SMA), as well as the development of collateral vessels in the area around the head of the pancreas. A stent was placed in the SMA stenosis to preserve intestinal blood flow in the SMA region after total pancreatectomy, which was performed 25 days after stent placement. The postoperative SMA blood flow was favorable, with no postoperative intestinal ischemia, and the patient had an uneventful postoperative course.

Expression of Ku80 in cervical cancer correlates with response to radiotherapy and survival.

To reveal the genes relevant for prediction of cervical cancer after radiotherapy, we previously carried out cDNA microarray experiments on primary cervical cancer comparing patients with a complete response (CR) and those with no change (NC). Some of these genes had already been associated with the radiation response, such as x-ray repair cross-complementing 5 (XRCC5), which was found more in radioresistant tumors than in radiosensitive ones. The aim of this study was to confirm the possible roles of XRCC5 mRNA levels by a real-time polymerase chain reaction method in 20 cervical cancers, and Ku80 protein, which is the gene product of XRCC5, using a histopathologic method of formalin-fixed sections of tumor biopsies in determining tumor response to radiotherapy and survival in 89 patients with cervical cancer. The levels of XRCC5 mRNA were 10(4.82) +/- 10(0.2) copies/microg total RNA in tumor tissues in the CR group (mean +/- standard deviation) and 10(4.95) +/- 10(0.32) copies/microg total RNA in those in the NC group. The levels of XRCC5 mRNA were not significantly different between the CR and NC groups. Histopathologic methods revealed 29.2% (26 of 89) of the patients to be Ku80-negative, with Ku80-positive findings in 70.8% (63 of 89). Of the Ku80-negative patients, 19 had CR, 3 had a partial response (PR), and 4 had NC. Of the Ku80-positive patients, 25 had CR, 22 had PR, and 16 had NC. Ku80-negative tumors showed significantly better responses than Ku80-positive ones, comparing CR and PR/NC responses (p = 0.01). In addition, overall survival was significantly better in the Ku80-negative patients as compared with those who were Ku80-positive (p = 0.04). The results of this study suggest that a low expression of Ku80 protein leads to radiosensitivity in cervical cancer and that Ku80 might play a role in treatment outcome.

Is whole-brain irradiation necessary for primary central nervous system lymphoma? Patterns of recurrence after partial-brain irradiation.

BACKGROUND: Neurotoxicity after whole-brain irradiation remains a major problem in the treatment of primary central nervous system lymphoma (PCNSL). To clarify whether whole-brain radiation is necessary for PCNSL, the authors retrospectively analyzed the outcome of patients treated with partial-brain irradiation. METHODS: A nationwide survey was performed regarding the treatment of PCNSL. Among 62 institutions surveyed, 7 were identified in which whole-brain irradiation was not necessarily employed. Questionnaires were sent to these institutions and 43 patients who had been treated using partial-brain fields since 1985 were collected. Thirty-two patients had solitary lesions and 11 had multiple lesions. Patterns of recurrence could be identified in 38 patients. RESULTS: The cumulative in-field and out-field recurrence rates at 5 years were 57% and 49%, respectively. Of 14 out-field recurrences, 2 occurred at the safety margin of the previous radiation field. The out-field recurrence rate was 45% in patients with a single lesion and 67% in those with multiple tumors (P = 0.79). The out-field recurrence rate was 22% for patients treated with safety margins of > or = 4 cm and 83% for those treated with safety margins of < 4 cm (P = 0.0079). The median survival time and the 5-year survival rate were 28.5 months and 20%, respectively, in the former group of patients and 15 months and 11%, respectively, in the latter group (P = 0.057). CONCLUSIONS: Focal radiotherapy with safety margins of < 4 cm appears to be associated with a very high rate of out-field recurrence, but the use of a radiation field with generous safety margins (> or = 4 cm) appears to be worth further investigation.