[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to update a previous scoring system for patients with skeletal metastases, that was proposed by Katagiri et al. in 2005, by introducing a new factor (laboratory data) and analyzing a new patient cohort. Between January 2005 and January 2008, we treated 808 patients with symptomatic skeletal metastases. They were prospectively registered regardless of their treatments, and the last follow-up evaluation was performed in 2012. There were 441 male and 367 female patients with a median age of 64 years. Of these patients, 749 were treated nonsurgically while the remaining 59 underwent surgery for skeletal metastasis. A multivariate analysis was conducted using the Cox proportional hazards model. We identified six significant prognostic factors for survival, namely, the primary lesion, visceral or cerebral metastases, abnormal laboratory data, poor performance status, previous chemotherapy, and multiple skeletal metastases. The first three factors had a larger impact than the remaining three. The prognostic score was calculated by adding together all the scores for individual factors. With a prognostic score of ≥7, the survival rate was 27% at 6 months, and only 6% at 1 year. In contrast, patients with a prognostic score of ≤3 had a survival rate of 91% at 1 year, and 78% at 2 years. Comparing the revised system with the previous one, there was a significantly lower number of wrongly predicted patients using the revised system. This revised scoring system was able to predict the survival rates of patients with skeletal metastases more accurately than the previous system and may be useful for selecting an optimal treatment.
[Show abstract][Hide abstract] ABSTRACT: In locally advanced Non-Small-Cell Lung Cancer (LA-NSCLC) patients treated with chemoradiotherapy (CRT), optimal surrogate endpoint for cure has not been fully investigated.
The clinical records of LA-NSCLC patients treated with concurrent CRT at Shizuoka Cancer Center between Sep. 2002 and Dec. 2009 were reviewed. The primary outcome of this study was to evaluate the surrogacy of overall response rate (ORR) and progression-free survival (PFS) rate at 3-month intervals (from 9 to 30 months after the initiation of treatment) for the 5-year survival rate. Landmark analyses were performed to assess the association of these outcomes with the 5-year survival rate.
One hundred and fifty-nine patients were eligible for this study. The median follow-up time for censored patients was 57 months. The ORR was 72%, median PFS was 12 months, and median survival time was 39 months.Kaplan-Meier curve of progression-free survival and hazard ratio of landmark analysis at each time point suggest that most progression occurred within 2 years. With regard to 5-year survival rate, patients with complete response, or partial response had a rate of 45%. Five-year survival rates of patients who were progression free at each time point (3-months intervals from 9 to 30 months) were 53%, 69%, 75%, 82%, 84%, 89%, 90%, and 90%, respectively. The rate gradually increased in accordance with progression-free interval extended, and finally reached a plateau at 24 months.
Progression-free survival at 2 years could be a reliable surrogate marker for the 5-year survival rate in LA-NSCLC patients treated with concurrent CRT.
BMC Cancer 01/2014; 14(1):18. · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The lateral electron-photon technique (LEPT) and intensity-modulated radiation therapy (IMRT) are commonly used for total scalp irradiation. However, the treatment planning and irradiation are laborious and time-consuming. We herein present the multijaw-size concave arc technique (MCAT) as a total scalp irradiation method that overcomes these problems. CT datasets for eight patients previously treated for angiosarcoma of the scalp were replanned using MCAT, LEPT, and IMRT. The MCAT was designed with a dynamic conformal arc for the total scalp, with a multileaf collimator to shield the brain. Two additional conformal arcs with a decreased upper-jaw position of the first dynamic conformal arc were used to reduce the cranial hotspots. The prescribed dose was 40 Gy (2 Gy/fraction) to 95% of the planning target volume (PTV, defined as the total scalp plus a 4 mm margin). MCAT was compared with LEPT and IMRT with respect to the PTV dose homogeneity (D5%-95%), underdosage (V < 90%), overdosage (V > 110%), doses to the brain, and the delivery time and monitor units (MUs) for single irradiation. We were able to formulate treatment plans for all three techniques that could deliver the prescription dose in all patients. MCAT was significantly superior to LEPT with respect to PTV dose homogeneity, overdosage, and underdosage, although MCAT was inferior to IMRT with respect to dose homogeneity and overdosage. The mean brain dose and high-dosage volume of all three techniques were low, but IMRT provided larger volume to the brain than did the other two techniques in the low dosage region. In MCAT, the mean delivery time could be reduced by approximately half or more, and the mean MUs could be reduced by at least 100 compared to the other two techniques. MCAT can achieve total scalp irradiation with substantially fewer MUs and a shorter delivery time than LEPT and IMRT.
Journal of applied clinical medical physics / American College of Medical Physics. 01/2014; 15(4):4786.
[Show abstract][Hide abstract] ABSTRACT: To compare proton beam therapy (PBT) and intensity-modulated radiation therapy (IMRT) with conformal radiation therapy (CRT) in terms of their organ doses and ability to cause secondary cancer in normal organs.
Five patients (median age, 4 years; range, 2--11 years) who underwent PBT for retroperitoneal neuroblastoma were selected for treatment planning simulation. Four patients had stage 4 tumors and one had stage 2A tumor, according to the International Neuroblastoma Staging System. Two patients received 36 Gy, two received 21.6 Gy, and one received 41.4 Gy of radiation. The volume structures of these patients were used for simulations of CRT and IMRT treatment. Dose--volume analyses of liver, stomach, colon, small intestine, pancreas, and bone were performed for the simulations. Secondary cancer risks in these organs were calculated using the organ equivalent dose (OED) model, which took into account the rates of cell killing, repopulation, and the neutron dose from the treatment machine.
In all evaluated organs, the mean dose in PBT was 20--80% of that in CRT. IMRT also showed lower mean doses than CRT for two organs (20% and 65%), but higher mean doses for the other four organs (110--120%). The risk of secondary cancer in PBT was 24--83% of that in CRT for five organs, but 121% of that in CRT for pancreas. The risk of secondary cancer in IMRT was equal to or higher than CRT for four organs (range 100--124%).
Low radiation doses in normal organs are more frequently observed in PBT than in IMRT. Assessments of secondary cancer risk showed that PBT reduces the risk of secondary cancer in most organs, whereas IMRT is associated with a higher risk than CRT.
[Show abstract][Hide abstract] ABSTRACT: Metastatic brain tumors have become a critical issue in clinical management for patients with cancer. We retrospectively analysed features of 105 patients with metastatic brain tumors from gastrointestinal cancer, who underwent treatment in our institute between September, 2002 and December, 2010. Treatment strategy was individualized according to the patient's systemic and neurologic conditions, size and location of the brain metastases, and expectant systemic treatment through our cancer board. Treatment outcome was significantly better in patients with RTOG RPA class 2 than in those with class 3(8.6 months vs 3.5 months: p<0.05). Metastatic brain tumors were diagnosed at 6.3/13.1/15.7 months after diagnosis of metastatic lung tumors from esophagus/stomach/colon cancers respectively. A third of the patients with metastatic brain tumor from rectal cancer presented without evident lung metastasis. In conclusion, patients with brain metastasis from gastrointestinal cancers can achieve improvement in survival with early diagnosis and multidisciplinary individualized treatments.
No shinkei geka. Neurological surgery 08/2013; 41(8):669-677. · 0.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients harboring sensitive epidermal growth factor receptor (EGFR) mutations show a dramatic response to treatment with EGFR tyrosine kinase inhibitors (TKIs). However, there have been no clinical reports in lung cancer patients that compare the time-to-response between radiotherapy and EGFR-TKIs.
We reviewed 17 and 32 consecutive patients with inoperable stage III/IV NSCLC who harbored sensitive EGFR mutations and who were treated with thoracic radiotherapy with or without chemotherapy and EGFR-TKIs, respectively.
There were statistically significant differences in time-to-partial response (PR) with regard to the treatment modalities (radiotherapy vs. EGFR-TKIs, median 57 days vs. 22 days, log-rank test, p=0.008).
EGFR-TKIs elicit tumor shrinkage earlier than does radiotherapy in patients with a sensitive EGFR mutation, suggesting that EGFR-TKIs may be useful for early symptom improvement in these patients.
Anticancer research 08/2013; 33(8):3279-84. · 1.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The aim of this retrospective study was to investigate the feasibility of primary treatment with extended-field irradiation and weekly cisplatin (extended-field concurrent chemoradiotherapy, EFCCRT) as initial therapy in patients with International Federation of Gynecology and Obstetrics IB1 to IIIB cervical cancer with paraaortic or high common iliac lymph node metastases. METHODS: Participants comprised patients with confirmed cervical cancer, showing paraaortic or high common iliac lymph node metastases on diagnostic imaging, treated with EFCCRT. Total external radiation doses were 50.4 Gy to the whole pelvis and 45.0 Gy to the lumbar paraaortic region. High-dose-rate intracavitary brachytherapy was performed to deliver a total dose of 18-24 Gy in 6-Gy fractions prescribed at point A. Weekly cisplatin (30-40 mg/m(2)) was given concurrently with radiotherapy. RESULTS: Twenty-four patients were treated. Median follow-up interval was 34 months. The dose of cisplatin was 30 mg/m(2) in 2 cases, 35 mg/m(2) in 8 cases, and 40 mg/m(2) in 14 cases. Twenty-two cases (92 %) received more than 160 mg/m(2) cisplatin. Ten cases (42 %) experienced acute grade 3/4 hematological toxicity, and 9 cases (38 %) experienced acute grade 3 nonhematological toxicity. No case presented late grade 3/4 toxicity. Three-year progression-free and overall survival rates were 54 % and 72 %, respectively. Eleven cases recurred during follow-up. Sites of recurrence were within the irradiation field in 4 cases, outside the field in 6 cases, and in both fields in 1 case. CONCLUSION: EFCCRT and high-dose-rate intracavitary brachytherapy for patients with paraaortic or high common iliac lymph node metastases from cervical cancer is feasible.
International Journal of Clinical Oncology 04/2013; · 2.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: To determine the recommended dose (RD) in concurrent conformal radiotherapy with S-1 and cisplatin chemotherapy for inoperable stage III non-small-cell lung cancer. PATIENTS AND METHODS: Eligible patients with inoperable stage III non-small-cell lung cancer, age ≥ 20 years, performance status 0-1 received 4 cycles of intravenous cisplatin (60 mg/m(2), day 1) and oral S-1 (80, 100, or 120 mg based on body surface area, days 1-14) repeated every 4 weeks. Radiation doses were 66, 70, and 74 Gy for arms 1, 2, and 3, respectively. RESULTS: A total of 24 patients were enrolled in our study, including 6 in arm 1, 6 in arm 2, and 12 in arm 3. The patients consisted of 14 men and 10 women, with a median age of 63 years (range, 44-73 years). The median follow-up was 27.3 months (range, 8.5-42.6 months) for all patients and 33.9 months (range, 15.2-42.6 months) for those still alive. Grade 3 febrile neutropenia, lung toxicities, and heart toxicities occurred in 2, 2, and 2 patients, respectively. Dose-limiting toxicity occurred in 2, none, and 1 patient in arms 1, 2, and 3, respectively. The median survival was not reached, and the 2-year survival rate was 70% (95% CI, 51%-89%). Two-year local relapse-free survival and distant metastasis-free survival were 74% (95% CI, 56%-92%) and 45% (95% CI, 25%-65%), respectively. CONCLUSIONS: High-dose radiotherapy with S-1 and cisplatin is feasible, and 74 Gy was determined as the recommended dose.
Clinical Lung Cancer 03/2013; · 2.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: As clinical trials for limited-disease small-cell lung cancer often exclude elderly patients due to comorbidities and a decline in organ function, the most suitable treatment for limited-disease small-cell lung cancer patients aged 75 years or older still remains unclear. METHODS: From July 2002 to June 2011, 20 consecutive patients aged 75 years or older, with Stage II to IIIB limited-disease small-cell lung cancer, were scheduled to be treated with concurrent or sequential chemoradiotherapy at the Shizuoka Cancer Center. We reviewed the medical charts of the patients and evaluated their characteristics, treatment compliance, toxicity and antitumor efficacy. RESULTS: Five patients were treated with concurrent chemoradiotherapy and the other 15 patients were scheduled to be treated with sequential chemoradiotherapy. Of these 15 patients, 12 were treated with four cycles of etoposide (80 mg/m(2), days 1-3, q3-4w) plus carboplatin (area under the curve 5, day 1, q3-4w), followed by thoracic radiotherapy. Of the five patients treated with concurrent chemoradiotherapy, discontinuation of chemotherapy/thoracic radiotherapy occurred in two patients due to toxicity and they suffered a prolonged decrease in performance status. Of the 12 patients treated with etoposide plus carboplatin followed by sequential thoracic radiotherapy, the response rate, median progression-free survival and median overall survival time were 91%, 244 and 601 days. CONCLUSIONS: These results suggest that concurrent chemoradiotherapy is not feasible for all limited-disease small-cell lung cancer patients aged 75 years or older. The alternative of four cycles of etoposide plus carboplatin followed by thoracic radiotherapy is a candidate for the standard treatment of limited-disease small-cell lung cancer patients in this age group. A further trial is warranted to develop and evaluate the optimal treatment for elderly patients with limited-disease small-cell lung cancer.
Japanese Journal of Clinical Oncology 12/2012; · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES:: Among patients with locally advanced lung adenocarcinoma, the frequency of epidermal growth factor receptor (EGFR) and KRAS mutations was unknown. In addition, it has not been fully evaluated about the role of these mutations treated with concurrent chemoradiotherapy (CCR). METHODS:: The clinical records of locally advanced lung adenocarcinoma patients treated with CCR at Shizuoka Cancer Center between September 2002 and December 2009 were reviewed. RESULTS:: Forty-four patients were eligible for this study. EGFR mutation was detected in 13 (29.5%) of 44 patients, and KRAS mutation was detected in 2 (6.5%) of 31 patients. Among EGFR mutation status known patients, overall response rate, median progression-free survival (PFS), and median survival time were 52.3%, 11.5 months, and 35.8 months, respectively. Overall response rate was significantly higher in EGFR mutant group than in EGFR wild-type group (76.9% vs. 41.9%, P=0.02), but this difference did not translate into a significant PFS benefit (9.6 vs. 13.2 mo, P=0.78). Locoregional relapse occured less frequently in patients with EGFR mutation than those with EGFR wild-type, but not significant (15.4% vs. 32.3%, P=0.46). Brain was the most frequent metastatic site of relapse in EGFR mutant group. CONCLUSIONS:: Among locally advanced lung adenocarcinoma, EGFR mutation was detected in 29.5% and KRAS mutation was detected in 6.5%. We were not able to detect a difference in PFS or overall survival between EGFR mutant and wild-type patients treated with conventional CCR. Locoregional relapse was approximately half in the EGFR mutant group compared with the EGFR wild-type group; however, this finding did not reach statistical significance.
American journal of clinical oncology 12/2012; · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Leptomeningeal metastasis (LM) is a devastating complication of systemic cancers. New therapies that have beneficial effects on primary cancers outside the central nervous system (CNS) have underscored the significance of LM. Intrathecal chemotherapy plus radiation therapy are less effective for LM from lung adenocarcinoma. We retrospectively studied outcomes of patients with LM from lung adenocarcinoma who underwent multidisciplinary treatments in our institute.
Four patients with LM from lung adenocarcinoma treated with EGFR-TKI, VP shunt and irradiation. Of those four, two presented with increased intracranial pressure, one with epilepsy, and the other with truncal ataxia. Treatment was indicated when LM was confirmed by MR images or cytology, and Karnofsky Performance Status scale was more than 40%, and life expectancy was more than three months if LM was controlled. EGFR mutation was not examined, because of the unsettled approval of Japanese public health insurance at the time of this study. The patients selected for treatment by EGFR-TKI were all Asian women who had never smoked. Treatment sequence was based on clinical symptoms depending on the individual situation.
The mean time from diagnosis of lung adenocarcinoma to LM onset was 28 (24 to 36) months. Mean survival time from LM diagnosis was 9 months. All patients died of LM. No patients suffered from peritoneal carcinomatosis or infection after VP shunt.
The triple modality combination of EGFR-TKI, VP shunt and radiation therapy may improve outcomes and symptoms of patients with LM from lung adenocarcinoma.
No shinkei geka. Neurological surgery 06/2012; 40(6):503-9. · 0.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Based on the results of phase I/II studies, S-1 plus cisplatin (CDDP) and vinorelbine (VNR) plus CDDP are commonly used chemoradiotherapeutic regimens for the treatment of non-small cell lung cancer(NSCCLC) in Japan. However, there have been no studies that have compared S-1 and CDDP combined with thoracic radiotherapy (TRT) with VNR and CDDP combined with TRT.
A total of 39 and 50 patients with stage III non-small cell lung cancer (NSCLC) were treated with S-1 and CDDP plus concurrent TRT, or with VNR and CDDP plus concurrent TRT, respectively, between 2002 and 2010.
In the S-1 plus CDDP plus TRT group, the median progression-free survival (PFS) and the median overall survival (OS) were 327 days and 1012 days, respectively. In the VNR plus CDDP plus TRT group, the median PFS and the median OS were 328 days and 905 days, respectively. The differences in the PFS and OS were not statistically significant. Grade 3 or more leukopenia and neutropenia were significantly more common in the VNR plus CDDP plus TRT group. Grade 3 or more thrombocytopenia, esophagitis and eruption tended to be more common in the S-1 plus CDDP plus TRT group.
Due to the difference in the toxicity profiles of the two combinations, S-1 plus CDDP plus TRT or VNR plus CDDP plus TRT should be selected depending on each patient's baseline characteristics.
Anticancer research 02/2012; 32(2):675-80. · 1.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There have been reports suggesting that continuous administration of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is advantageous for patients in which disease progression was observed after the establishment of clinical benefit from EGFR-TKIs. We retrospectively evaluated the clinical course of patients who received continuous administration of EGFR-TKIs after disease progression was detected solely in bone lesions.
The medical records of patients administered gefitinib or erlotinib between 2002 and 2010 were reviewed. We evaluated the progression-free survival (PFS) and overall survival (OS) in patients who had bone metastases after the establishment of clinical benefit from EGFR-TKI and who received radiation therapy for the bone lesion and continuous treatment with EGFR-TKI.
Ten patients were enrolled in this study. The median PFS and OS were 88 days and 330 days, respectively. Furthermore, a longer duration from the start of first EGFR-TKI to detection of bone metastases (p=0.0049) was identified as being significantly associated with a longer PFS.
Our data suggest that continuous administration of EGFR-TKI is a treatment option for patients with bone metastases who previously benefited from therapy with EGFR-TKI.
Anticancer research 12/2011; 31(12):4519-23. · 1.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The study was performed to evaluate radiotherapy for patients with intramedullary spinal cord metastasis (ISCM) and to identify the clinical features of ISCM. The subjects were 18 patients (8 men, 10 women) with ISCM who underwent radiotherapy between September 2002 and February 2008. The primary lesions were lung cancer in 8 patients (2 small cell, 6 non-small cell), breast cancer in 6, malignant melanoma in 2, renal cell carcinoma in 1, and rectal cancer in 1 patient. Diagnosis, symptoms and survival of these patients were compared with those for 544 patients with vertebral metastases who underwent radiotherapy at the same institute between September 2002 and November 2006. In the 18 patients with ISCM, the 6-month survival rate after radiotherapy was 36% and the median survival period was 4.0 months. Ten patients had neurological improvement or pain relief after radiotherapy. Brain metastases were six fold more frequent in the patients with ISCM than in those with vertebral metastasis [89% vs. 15%, p = 0.001]. At the time of radiotherapy, back pain in patients with vertebral metastasis was more frequent [97% vs. 33%, p = 0.001] but neurological deficits were less common [24% vs. 100% , p = 0.001]. Most ISCM cases were diagnosed by contrast-enhanced MRI, with detection by contrast-enhanced CT in only 3/18 cases (17%). ISCM has a poor prognosis and most patients have neurological deficits that impair quality of life. Early diagnosis by MRI is important for suspected ISCM to allow initiation of radiotherapy before development of neurological deficits.
Journal of Radiation Research 07/2011; 52(5):641-5. · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the safety and efficacy of concurrent vinorelbine and thoracic radiotherapy in elderly patients with locally advanced non-small-cell lung cancer (NSCLC).
Eligible patients were 71 years of age or older with unresectable Stage III NSCLC. Patients were treated with thoracic radiotherapy (60 Gy) and concurrent vinorelbine (20 mg/m(2) in Level 1 and 25 mg/m(2) in Level 2) on Days 1 and 8 every 3 weeks for two cycles, followed by adjuvant vinorelbine (25 mg/m(2)) on Days 1 and 8 every 3 weeks for two cycles.
Four patients were enrolled at Level 1. One patient experienced Grade 3 febrile neutropenia at Level 1 and the dose was escalated to Level 2. At Level 2, 2 of 6 patients experienced dose-limiting toxicities (Grade 4 neutropenia in 1 patient and Grade 3 infection in another). Three of 6 patients developed late Grade 2 or 3 pneumonitis. Therefore, the dose was de-escalated to Level 1. An additional 6 patients were enrolled at Level 1, 4 of whom experienced dose-limiting toxicities (incomplete radiotherapy because of Grade 2 pneumonitis in 1 patient and Grade 3 infection in 1, Grade 3 febrile neutropenia in 1, and Grade 3 esophagitis in 1). Moreover, late Grade 3 pneumothorax and Grade 5 pneumonitis occurred in 1 and 1 patient, respectively. Overall, Grade 2, 3 and 5 pneumonitis occurred in 3, 3, and 1 among 16 patients, respectively.
Concurrent vinorelbine and thoracic radiotherapy resulted in a high incidence of severe pneumonitis when the standard dose of this agent was used for elderly patients. We therefore recommend caution in the use of this regimen and schedule for elderly patients.
International journal of radiation oncology, biology, physics 05/2011; 82(5):1777-82. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Based on previous reports, patients who experience isolated central nervous system (CNS) failure may not have systemic acquired resistance to EGFR-TKI therapy. However, because there are few articles that have reported on the clinical efficacy of continuous EGFR-TKI administration following progressive disease (PD) in isolated CNS metastasis, we retrospectively investigated the possibility of using the treatment.
From July 2002 to December 2009, 17 non-small cell lung cancer patients showed isolated CNS failure after clinical benefit (partial response or stable disease longer than 6 months) from EGFR-TKIs and continuously received EGFR-TKIs following radiotherapy (whole brain radiotherapy or stereotactic radiotherapy) to the CNS metastases.
The response rate and the disease control rate of CNS lesions were 41% and 76%, respectively. The median progression free survival, extracranial progression free survival and the median overall survival time were 80 days, 171 days and 403 days, respectively. The toxicities which were observed during the first EGFR-TKI treatments were sustained, but did not worsen during this study period. The acute toxicities caused by radiotherapy to the CNS were controllable. There were no remarkable late toxicities related to the treatment.
Continuous administration of EGFR-TKI following radiotherapy after PD in isolated CNS metastasis appears to be a valid treatment option.
Lung cancer (Amsterdam, Netherlands) 05/2011; 74(3):457-61. · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Brain metastasis from esophageal carcinoma has been considered rare and survival following esophageal carcinoma with distant metastasis is poor. The purpose of this report was to clarify cumulative incidence and risk factors for brain metastasis after chemoradiotherapy for esophageal carcinoma, and to consider recommended treatments for brain metastasis from esophageal carcinoma. We reviewed 391 patients treated with chemoradiotherapy. Median age was 65 years. Clinical stages were I, II, III, and IV in 32, 47, 150, and 162 patients, respectively. Brain imaging was performed usually when patients revealed neurological symptoms. The 3-year cumulative incidence of brain metastasis after chemoradiotherapy was 6.6%. There were 4 patients with single metastasis and 8 with multiple metastases. Initial clinical stages were II, III, and IV in 1, 2, and 9 patients, respectively. Histology included squamous cell carcinoma in 10 patients and others in 2 patients. Univariate analysis demonstrated M factor, distant lymph node relapse, and recurrent lung and liver metastasis as significant risk factors of brain metastasis (P < 0.05). Median survival time after diagnosis of brain metastasis was 2.1 months. Brain metastasis was not directly related to cause of mortality. The causes were extracranial tumor deterioration in 8 patients and infection in 4 patients. Brain metastasis may increase in the future with improving survival from esophageal carcinoma. However, considering the poor survival after diagnosis of brain metastasis, short-term palliative therapy for brain metastasis appears preferable to vigorous long-term therapy.
Journal of Radiation Research 04/2011; 52(4):509-15. · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Skull metastases are malignant bone tumors which are increasing in incidence. The objectives of this study were to characterize the MR imaging features, locations, and extent of metastatic skull tumors to determine the frequency of the symptomatic disease, and to assess patient outcomes. Between September 2002 and March 2008, 175 patients undergoing routine head MR imaging were found to have metastatic skull tumors. Contrast-enhanced study with fat suppression was used in some cases when required. Classification of metastases was simplified to three yes/no questions: first, with regard to location (either in the calvarium or in the cranial base); second, with regard to distribution within the plane of the cranial bone (either "circumscribed" meaning clearly demarcated and confined to one bone, or "diffuse" and likely to spread across a suture to another bone); and third, with regard to invasion ("intraosseous" in cranial bones only, or "invasive" spreading from the skull, either out into the scalp or inward to the dura and perhaps further in). Primary sites were breast cancer (55%), lung cancer (14%), prostate cancer (6%), malignant lymphoma (5%), and others (20%). The mean time from primary diagnosis to skull metastasis diagnosis was 71 months for cases of breast cancer, 26 months for prostate cancer, 9 months for lung cancer, and 4 months for malignant lymphoma. Calvarial circumscribed intraosseous metastases were found most frequently (27%). The patients were mainly asymptomatic. However, some patients suffered from local pain or cranial nerve palsies that harmed their quality of life. Treatment, mainly for symptomatic cases, was by local or whole-skull irradiation. Metastatic skull tumors are not rare, and most are calvarial circumscribed intraosseous tumors. MR images contribute to understanding their type, location, and multiplicity, and their relationship to the brain, cranial nerves, and dural sinuses. Radiation therapy improved the QOL of patients with neurological symptoms.
Journal of Neuro-Oncology 11/2010; 104(1):239-45. · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: After stereotactic radiosurgery (SRS) for brain metastases, delayed radiation effects with mass effect may occur from several months to years later, when tumors may also recur. Aggressive salvage treatment would be beneficial for patients with recurrence, but may be contraindicated for those with dominant radiation effect. Conventional magnetic resonance (MR) imaging does not provide sufficient information to differentiate delayed radiation effects from tumor recurrence. Positron emission tomography, MR spectroscopy, and other modalities sometimes may lead to false findings of tumor recurrence. We prospectively applied perfusion MR imaging for the management strategy after SRS because it gives microvascular information about the lesions. Twenty-eight lesions were enlarged on serial MR images in 27 patients 2-35 months (median: 11.8 months) after SRS for metastatic brain tumors. Each patient underwent MR perfusion imaging within a month after appearance of the growing enhanced lesion. To calculate the relative cerebral blood volume ratio (rCBV ratio), the regions of interest were located in the enhanced areas on the contrast-enhanced T1-weighted images and compared with the corresponding contralateral normal brain tissue. They were then followed-up with scheduled MR images with gadolinium enhancement at 1 to 2-month intervals afterward. Lesions which progressively increased in size on MR images were diagnosed as recurrences; lesions which disappeared or decreased in size were diagnosed as radiation necrosis. In addition, two lesions surgically removed were diagnosed by pathological examination. Follow-up MR images revealed that 21 of 28 lesions were radiation necrosis. Five lesions were diagnosed as recurrence on MR images, and the other two lesions were revealed as recurrence by pathological examination. An rCBV ratio of greater than 2.1 provided the best sensitivity and specificity for identifying recurrent metastatic tumors, at 100 and 95.2%, respectively. Perfusion MR imaging provides useful, less invasive and in-vivo information for management of growing lesions after SRS, and rCBV may be a valuable index for this diagnostic purpose.
Journal of Neuro-Oncology 08/2010; 99(1):81-8. · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Long- and short-course radiotherapy have similar outcomes in the treatment of spinal metastases. Long-course radiotherapy is recommended for patients with good predicted survival to reduce the risk of in-field recurrence, whereas short-course radiotherapy is used for those with poor predicted survival. Therefore, prediction of prognosis and local control is required for selecting the optimal course of radiotherapy.
The subjects were 603 patients with spinal metastases who received radiotherapy at the Shizuoka Cancer Center Hospital between September 2002 and February 2007. Factors associated with survival and local control were retrospectively investigated by multivariate analyses. Local recurrence was defined as regrowth within the irradiated field or exacerbation of symptoms such as pain and motor deficits.
Of the 603 patients, 555 (92%) were followed for 12 months or until death. The survival rates after 6, 12, and 24 months were 50%, 32%, and 19%, respectively, with a median survival of 6.2 months. The median survival periods after long- and short-course radiotherapy were 7.9 and 1.8 months, respectively. In multivariate analysis, primary tumor site, good performance status, absence of previous chemotherapy, absence of visceral metastasis, single bone metastasis, younger age, and nonhypercalcemia were associated with good survival. The local control rates after 6, 12, and 24 months were 91%, 79%, and 69%, respectively, and non-mass-type tumor, breast cancer, and absence of previous chemotherapy were predictors of good local control.
Identification of factors associated with good local control and survival may allow selection of an optimal radiotherapy schedule for patients with spinal metastases.
International journal of radiation oncology, biology, physics 04/2010; 79(1):208-13. · 4.59 Impact Factor