Prognostic Parameters after Surgery for Adrenal Metastases: a Single Institution Experience

Background: Clinically isolated adrenal metastases are rare and therefore present a therapeutic challenge. We report our experience with surgery of adrenal metastases and analyze factors that may influence postoperative survival. Methods: A consecutive series of 31 patients (16 male, 15 female) underwent adrenal surgery for metastases at a single institution over 10-year period (1999–2008). The Kaplan-Meier method and log-rank test were used to determine overall survival. Potential prognostic factors were identified by univariate and multivariate Cox regression analysis. Results: The primary tumor diagnoses were non-small-cell lung carcinoma (NSCLC) 20, colorectal carcinoma 5, renal cell carcinoma (RCC) 2, malignant melanoma and breast carcinoma, one each. The median survival was 12 months, with one year and five year survival of 21% and 3.4% respectively. According to multivariate analysis independent prognostic factors of favorable survival were disease free interval (DFI) longer than 12 months (Hazard ratio (HR) = 0.28, 95%CI = 0.09–0.90), potentially curative resection (Hazard ratio (HR) = 0.35, 95%CI = 0.12–1.00) and postoperative radiotherapy of adrenal bed (Hazard ratio (HR) = 0.33, 95%CI = 0.12–0.91).

Conclusions: Overall survival after surgery for adrenal metastases is poor. In multivariate analyses, survival is influenced by DFI, curative resection, and postoperative radiotherapy.     

Evaluation of bone metastases from renal cell carcinoma

Forty-two cases of bone metastasis from renal cell carcinoma were examined. Thirty of the cases had bone metastases at the time of renal cell carcinoma. Bone metastasis appeared after treatment of the primary site in 12 cases. Fifteen cases had only bone metastasis and another 27 had metastasis in multiple organs. The total cause-specific survival curve of these patients was 10% at 5 years. All patients with bone metastases died of cancer within 5 years after the bone metastases had developed. There was no significant difference in the survival rate between patients with bone metastases and patients with lung metastases. We investigated the prognostic value of laboratory studies in bone metastases of renal cell carcinoma. However, no significant markers were detected for bone metastases. The 6 patients were treated with decompressed laminectomy (2), wide resection (3) and excision of the metastatic lesions (3). The quality of life was improved in all the patients although they died of cancer.     

Radiosurgery in patients with renal cell carcinoma metastasis to the brain: long-term outcomes and prognostic factors influencing survival and local tumor control

OBJECT: Renal cell carcinoma is a leading cause of death from cancer and its incidence is increasing. In many patients with renal cell cancer, metastasis to the brain develops at some time during the course of the disease. Corticosteroid therapy, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, the median survival in patients with renal cell carcinoma metastasis is approximately 3 to 6 months. In this study the authors examined the efficacy of gamma knife surgery in treating renal cell carcinoma metastases to the brain and evaluated factors affecting long-term survival. METHODS: The authors conducted a retrospective review of 69 patients undergoing stereotactic radiosurgery for a total of 146 renal cell cancer metastases. Clinical and radiographic data encompassing a 14-year treatment interval were collected. Multivariate analyses were used to determine significant prognostic factors influencing survival. The overall median length of survival was 15 months (range 1-65 months) from the diagnosis of brain metastasis. After radiosurgery, the median survival was 13 months in patients without and 5 months in those with active extracranial disease. In a multivariate analysis, factors significantly affecting the rate of survival included the following: 1) younger patient age (p = 0.0076); 2) preoperative Karnofsky Performance Scale score (p = 0.0012); 3) time from initial cancer diagnosis to brain metastasis diagnosis (p = 0.0017); 4) treatment dose to the tumor margin (p = 0.0252); 5) maximal treatment dose (p = 0.0127); and 6) treatment isodose (p = 0.0354). Prior tumor resection, chemotherapy, immunotherapy, or whole-brain radiation therapy did not correlate with extended survival. Postradiosurgical imaging of the brain demonstrated that 63% of the metastases had decreased, 33% remained stable, and 4% eventually increased in size. Two patients (2.9%) later underwent a craniotomy and resection for a tumor refractory to radiosurgery or a new symptomatic metastasis. Eighty-three percent of patients died of progression of extracranial disease. CONCLUSIONS: Stereotactic radiosurgery for treatment of renal cell carcinoma metastases to the brain provides effective local tumor control in approximately 96% of patients and a median length of survival of 15 months. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including radiosurgery can offer patients an extended survival.     

Prognostic factors and survival after pulmonary resection of metastatic renal cell carcinoma

OBJECTIVE: Pulmonary metastasectomy as well as immunotherapy have reproducible, albeit limited efficacy in advanced renal cell carcinoma (RCC). We examined whether metastasectomy improved overall survival compared with results of immunotherapy. METHODS: Between 1975 and 2003, 64 patients (41 men, 23 women) underwent pulmonary resection of metastatic RCC. Only patients who met the criteria for potentially curative operation, that means, control of primary tumor, ability to resect metastatic disease and no other extrapulmonary metastases, were included. RESULTS: The overall 5-year survival was 33.4% (median survival: 39.2 months). A significant longer survival was observed using multivariate analysis in patients with complete pulmonary resection (R0), with a 5-year survival of 39.9% and a median survival of 46.6 months in correlation to patients with incomplete resection (5-year survival 0%, median survival 13.3 months). In multivariate analysis patients with synchronous metastases had a significant worse prognosis in correlation to patients with metachronous metastases. The 5-year survival of curative resected patients with metachronous metastases was 43.7% versus 0% for synchronous metastases, respectively. In patients with solitary metastasis and R0 resection, we observed a 5-year survival of 49%, whereas the rate was 23% in patients with more than a single metastasis. When establishing prognostic groups as suggested by the International Registry based on the risk factors disease-free interval, number of metastasis and complete resection the group with the best prognosis showed a 5-year survival of 52% (median survival 75.2 months). CONCLUSION: Metastasectomy nowadays is the best treatment option in cases with technical resectable metastases with as much as possible good prognostic factors (metachronous metastases with long DFI, number up to 6 metastases).     

Surgical treatment of osseous metastases in patients with renal cell carcinoma.

Forty-five patients who underwent surgical treatment for osseous metastases secondary to renal cell carcinoma between 1980 and 1998 were reviewed. The diagnosis was confirmed histologically in all patients. The mean age of the 34 men was 61.5 +/- 9 years and of the 11 women 55.2 +/- 17.6 years. The most common locations of the metastases were the spine (15 patients), the pelvis (eight patients), and the femur (11 patients). In 21 patients, the renal cell carcinoma was diagnosed when the osseous metastasis was detected. The time from diagnosis of the primary tumor to metastasis in the remaining patients ranged from 0 to 23 years (mean, 3 +/- 5 years). At presentation, 19 patients had a singular lesion. Nine patients had multiple osseous metastases and 17 patients had additional visceral involvement. In seven patients, a wide or radical resection was done; in 35 patients, a palliative procedure was done; and in three patients, only a diagnostic procedure was done. For the whole group, the survival was 49% after 1 year, 39% after 2 years, and 15% after 5 years. Only the extent of the disease and the latency period between primary tumor diagnosis and first detection of osseous metastasis could be identified as independent factors of survival. Nine patients with solitary metastasis to the bone more than 12 months after resection of the primary tumor showed a 5-year survival of 54%.     

Prognostic factors of renal cell carcinoma with extension into inferior vena cava

Objective:   To evaluate the prognosis of our series of patients with renal cell carcinoma (RCC) and tumor thrombus involving inferior vena cava (IVC) treated with nephrectomy and thrombectomy.
Methods:   In 46 patients with unilateral RCC extending into IVC who underwent nephrectomy and thrombectomy (T3b in 38 patients, T3c in 6, T4 in 2, N+ in 15, M1 in 21), overall and cancer-specific survival rates were estimated, and the univariable and multivariable analysis were carried out to determine the prognostic factors among age, gender, performance status, fever, inflammatory laboratory parameters, nodal and distant metastasis, tumor thrombus level, pathological parameters and postoperative interferon-α administration.
Results:   The median age was 66.5 (range 35–79) years. The median follow-up was 18.0 (mean 36.7 ± 38.7) months. The overall and cancer-specific 5-year survival rates were 32.9% and 40.0%, respectively. The univariate analysis revealed that fever (hazard ratio: HR 4.03), C-reactive protein (HR 4.89), grade of tumor cell (HR 3.83), and lymph node metastasis (HR 5.99) were independent prognostic factors of cause-specific survival in all patients. The multivariate analysis demonstrated that lymph node metastasis (HR 4.13) was the only independent prognostic factor of cause-specific survival. The extension level or postoperative interferon-α administration did not influence the prognosis of patients with tumor thrombus involving IVC.
Conclusions:   Aggressive surgery should be considered first in RCC patients with any levels of tumor thrombus. However, patients with both IVC involvement and nodal metastasis showed significantly poor prognosis, and development of novel intensive multidisciplinary therapies will be needed.     

Is Memorial Sloan-Kettering Cancer Center risk classification appropriate for Japanese patients with metastatic renal cell carcinoma in the cytokine era?

ObjectivesWe investigated the prognosis of Japanese patients with metastatic renal cell carcinoma (RCC), and analyzed the validity of Memorial Sloan-Kettering Cancer Center (MSKCC) risk classification.Materials and methodsThe endpoint of the present study was overall survival. Relationships between overall survival and potential prognostic factors were assessed using the Cox proportional hazard model with a step-wise procedure. Prognostic assessment was also performed according to the MSKCC risk classification. The predictive accuracy of the MSKCC risk classification was measured employing the concordance index.ResultsThe median survival for all patients was 22 months (95% CI, 19–28 months). The eight factors were identified as independent prognostic factor; time from initial diagnosis to metastasis, low hemoglobin (Hb), lactate dehydrogenase (LDH), corrected serum calcium (cCa), C-reactive protein (CRP), and the presence or absence of liver metastasis, bone metastasis, and lymph node metastasis. When the MSKCC risk classification was applied to patients, the median overall survival was not reached and 26 and 10 months in the patients classified as favorable, intermediate, and poor risk, respectively. The c-index was 0.73.ConclusionsThe prognosis of Japanese metastatic renal cell carcinoma patients may be better than that of previous studies from North America or Europe. Although there are some differences in the rate of patients in the risk groups and survival time by risk group between these patients, the MSKCC risk classification may be applicable for Japanese patients with metastatic renal cell carcinoma.     

Treatment of osseous metastases in patients with renal cell carcinoma

The records of 99 patients treated at one institution for osseous metastases secondary to renal cell carcinoma were reviewed. Patients were followed up for at least 24 months or until death. Survival was analyzed with respect to age, gender, disease-free interval, location of osseous metastases, number of osseous metastatic sites, resection of osseous metastases, and primary tumor resection. The mean age of the 72 men and 27 women was 60 years (range, 34-82 years) and the mean followup was 20 months (range, 2-81 months). Twenty-six patients (26%) had a solitary osseous metastasis, 47 patients (48%) had multiple osseous metastases, and 26 patients (26%) had additional visceral involvement such as the lung and brain at the time of diagnosis. In 49 patients (49%), the renal cell carcinoma was diagnosed concurrently with detection of the osseous metastasis. The presence of one osseous renal carcinoma metastasis, wide resection of the lesion, and a history of nephrectomy were identified as independent predictors of survival in patients with renal cell carcinoma. The eight patients who had wide resection of a solitary osseous metastasis in combination with a nephrectomy had a disease-specific survival rate of 100% (mean followup, 69 months; range, 24-76 months). Patients who present with these characteristics are candidates for aggressive surgical treatment with curative intent.     

Clinical prognostic factors associated with outcome in patients with renal cell cancer with prior tyrosine kinase inhibitors or immunotherapy treated with everolimus

BackgroundThe mTOR inhibitor, everolimus, is approved for the treatment of metastatic renal cell carcinoma (RCC). However, prognostic models are needed to determine the patients who would most benefit from this therapy. We have developed a model based on clinical parameters and patient stratification into risk groups to predict patients with RCC who will derive the most benefit from treatment with everolimus.MethodsWe assessed retrospective data on 57 patients with RCC who received everolimus after previous treatment with immunotherapy or tyrosine kinase inhibitors to identify prognostic factors for progression-free survival (PFS) and overall survival (OS). In the original phase II study, patients received 10 mg of everolimus daily without interruption and were assessed every other week for the first 8 weeks on therapy and every 4 weeks thereafter. Kaplan-Meier analysis was used to calculate OS and PFS. Univariate and multivariate analyses were constructed using the Cox proportional hazards model and a stepwise procedure to validate the data.ResultsWe grouped patients according to risk: 0 prognostic factors indicated favorable risk, 1 to 2 factors intermediate risk, and≥3 factors poor risk. We found notable differences in median OS (29.6 mo for favorable risk, 14.3 mo for intermediate risk, and 7.2 mo for poor risk). Three risk factors (prior radiation treatment, no lung metastasis present at the start of treatment, and lymphocytes<25 cells/µl) in the multivariate analysis were found to be associated with PFS, and 4 risk factors were found to be associated with OS (bone metastasis at start of treatment, LDH>1.5×upper limit of normal, alkaline phosphatase>120 U/l, and lymphocytes<25 cells/µl).ConclusionsOur prognostic model includes 3 readily available clinical parameters for PFS and 4 readily available clinical parameters for OS to help stratify patients into poor, intermediate, and favorable prognosis groups for the treatment of everolimus in clear cell RCC. These intriguing results warrant further study in a larger patient population to validate the findings.     

The Prognostic Importance of Metastatic Site in Men with Metastatic Castration-resistant Prostate Cancer

The presence of visceral metastases is adversely prognostic in men with metastatic castration-resistant prostate cancer (mCRPC), but the prognostic impact of the site of visceral metastasis is unclear. Men with mCRPC in the TAX 327 phase 3 trial receiving docetaxel or mitoxantrone every 3 wk or weekly docetaxel, each with prednisone, were analyzed retrospectively to study the impact of the site of visceral metastasis on overall survival (OS). Patients were assessed for OS by site of metastases: liver with or without other sites, lung with or without bone or lymph nodes, bone plus lymph nodes, bone only, and lymph nodes only. Cox proportional hazards regression, adjusted for treatment and stratification factors, was performed. Men with liver metastases with or without other metastases had shorter median OS (10.0 mo; 95% confidence interval [CI], 5.4–11.5) than men with lung metastases with or without bone or nodal metastases (median OS: 14.4 mo; 95% CI, 11.5–22.4). Men with lymph node-only disease had the best median OS (26.7 mo; 95% CI, 22.3–34.2), followed by men with bone-only metastases (median OS: 19.0 mo; 95% CI, 18.2–20.7) and bone-plus-node disease (median OS: 15.7 mo; 95% CI, 14.4–17.2). Thus, pattern of spread including site of visceral metastasis confers a differential prognostic impact. These data require validation and may inform trial design and therapy.     

Breast cancer subtypes and outcomes of central nervous system metastases

Central nervous system (CNS) metastases are detected in up to one third of patients with advanced breast cancer, but their incidence and outcomes by breast cancer subtypes are not precisely documented. Herein, we retrospectively analyzed clinicopathologic data of 259 breast cancer patients with CNS metastases to evaluate the association between breast cancer subtypes and CNS metastasis. The patient groups were classified according to their hormone receptor status and HER-2 expression. Median follow-up time among the patients was 42 months and median survival after CNS metastasis detection was 7.8 months. In HER-2 overexpressing group, median time period between the diagnosis of breast cancer and the detection of CNS metastasis (15.9 months) was significantly shorter compared to the other groups (p = 0.01). The triple negative group had the shortest median survival time after CNS metastasis (6.6 months), although statistically not significant (p = 0.3). In multivariate Cox regression analyses, having solitary CNS metastasis (HR 0.4, 95% CI; 0.2–0.7, p = 0.004), and receiving chemotherapy after CNS metastasis (HR 0.4, 95% CI; 0.287–0.772, p = 0.003) were independent prognostic factors for increasing survival after CNS metastasis. In conclusion, new and effective treatment strategies are required for breast carcinoma patients with brain metastasis considering the positive effect of the treatment on survival.     

Cytoreductive nephrectomy for pT3b–T4 M1 renal cell carcinoma in 39 patients: Single center analysis

We reviewed cytoreductive nephrectomy for pT3b–T4 renal cell carcinoma with metastasis and evaluated the prognostic factors for cancer‐specific survival. A total of 39 patients who underwent cytoreductive nephrectomy for renal cell carcinoma with pathological T3b–T4 (2009 Union for International Cancer Control consensus) from 1986 to 2011 in our hospital were the participants in this study. Prognostic factors for cancer‐specific survival were analyzed. The median patient age was 64 years (range 31–84). Pathological T3b, T3c and T4 were found in 24 (61%), one (3%) and 14 (36%) patients, respectively. The distribution of the histological type was clear cell type in 34 (87%), papillary type in two (5%) and any type of renal cell carcinoma with a sarcomatoid component in three patients (8%). The median overall and cancer‐specific survival was 7.5 and 7.6 months, respectively. Low‐grade performance status, regional lymph node metastasis, higher pT stage and histological type were prognostic factors for cancer‐specific survival on univariate analysis. On multivariate analysis, lymph node metastasis, higher pT stage and histological type (non‐clear cell or sarcomatoid component) were significant predictors for cancer‐specific survival. With cytoreductive nephrectomy for patients with pT4, lymph node metastasis and non‐clear cell histology, we have to be particularly careful in terms of cancer control.     

Long-term results after pulmonary resection of renal cell carcinoma metastases

BACKGROUND: Until now no conclusive data exist regarding the factors influencing long-term survival after pulmonary resection of renal cell carcinoma metastases. The aim of the present study, therefore, was to discover definitive prognostic factors for survival using a large and homogeneous single center patient cohort. METHODS: Between 1980 and 2000, 105 patients, after curative resection of lung metastases from renal cell carcinoma, were followed in this long-term study. These patients underwent a total of 150 surgical procedures. Survival analysis was done using the Kaplan-Meier method and the log-rank test. Multivariate analysis of prognostic factors was performed using the Cox multivariate proportional hazard model. RESULTS: Median survival after curative resection reached 43 months (range, 1 to 218 months). Survival at 3, 5, and 10 years was 54%, 40%, and 33%, respectively. Univariate analysis revealed that a complete resection, a less than 4-cm diameter of the metastases and tumor-free lymph nodes at the time of primary operation, were highly significant dependent prognostic factors (p < 0.001). These factors were also shown to be independent prognostic factors as suggested by multivariate analysis (p < 0.05). CONCLUSIONS: The size of the metastatic nodule, the completeness of pulmonary resection, and the lymph node status at the time of nephrectomy are the most important prognostic factors that influence survival after resection of pulmonary metastases. Recurrence of resectable pulmonary metastases does not impair survival, thus favoring repeated resection in patients with recurrent disease.     

Pancreatic Metastasis From Renal Cell Carcinoma: Which Patients Benefit From Surgical Resection?

Background Pancreas is a possible site of metastases from renal cell carcinoma (RCC). The aim of this study was to define the role of surgery in their treatment. Methods We retrospectively analyzed 36 patients with pancreatic metastasis from RCC observed between January 1998 and February 2006. Patients were categorized into three risk groups according to the modified Memorial Sloan-Kettering prognostic factors model. Results Resective surgery was performed in 23 patients, as follows: 11 distal pancreatectomy, 5 enucleation, 4 pancreatoduodenectomy, 2 total pancreatectomy, and 1 middle pancreatectomy. No perioperative mortality was observed; the morbidity rate was 47.8%. All patients who underwent resection belonged to the favorable risk group. Surgical resection was excluded in 13 cases because of locally advanced disease (2 cases) or extrapancreatic disease (11 cases); 5 of these patients were at favorable, 7 at intermediate, and 1 at poor risk. In patients undergoing surgery, the 5-year actuarial survival rate was 88%, and median disease-free survival was 44 months. Patients who did not undergo surgery had a 5-year survival rate of 47%, with a median survival time of 27 months (P = .02). Conclusions Patients with pancreatic metastases from RCC belonging to a favorable risk group are candidates for resection, even in the presence of another metastatic site or multifocal pancreatic disease.     

Osseous metastases secondary to renal cell carcinoma

We present the distribution of metastases and clinical course of 252 patients with osseous metastases secondary to renal cell carcinoma. Symptoms of the metastases were the presenting complaint in 48 per cent of patients (including 37 with pathologic fractures); the axial skeleton was the most commonly involved site. Despite earlier reports that nephrectomy lenthened survival for patients with osseous metastases, our data showed this to be true only for patients with a solitary osseous metastasis. Patients with multiple osseous metastases had survival rates no better than patients with soft tissue or mixed lesions—whether or not nephrectomy was performed.     

Radiosurgery for non-small cell lung carcinoma metastatic to the brain: long-term outcomes and prognostic factors influencing patient survival time and local tumor control

OBJECT: Lung carcinoma is the leading cause of death from cancer. More than 25% of those patients with lung cancer develop a brain metastasis at some time during the course of their disease. Corticosteroid therapy, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, the median survival for patients with lung carcinoma metastasis is approximately 3 to 6 months. The authors examine the efficacy of gamma knife radiosurgery (GKS) for treating non-small cell lung carcinoma (NSCLC) metastases to the brain and evaluate factors affecting long-term patient survival. METHODS: A retrospective review of 273 patients who had undergone GKS to treat a total of 627 NSCLC metastases was performed. Clinical and neuroimaging data encompassing a 14-year treatment interval were collected. Univariate and multivariate analyses were performed to determine significant prognostic factors influencing patient survival. The overall median patient survival time was 15 months (range 1-116 months) from the diagnosis of brain metastases. The median survival was 10 months from GKS treatment in those patients with adenocarcinoma and 7 months for those with other histological tumor types. In patients with no active extracranial disease at the time of GKS, the median survival time was 16 months. In multivariate analyses, factors significantly affecting survival included: 1) female sex (p = 0.014); 2) preoperative Karnofsky Performance Scale score (p < 0.0001); 3) adenocarcinoma histological subtype (p = 0.0028); 4) active systemic disease (p = 0.0001); and 5) time from lung cancer diagnosis to the development of brain metastasis (p = 0.0074). Prior tumor resection or whole-brain radiation therapy did not correlate with extended patient survival time. Postradiosurgical imaging of brain metastases revealed that 60% decreased, 24% remained stable, and 16% eventually increased in size. Factors affecting local tumor control included tumor volume (p = 0.042) and treatment isodose (p = 0.015). Fourteen patients (5.1%) later underwent craniotomy and tumor resection for tumor refractory to GKS or a new symptomatic metastasis. CONCLUSIONS: Gamma knife surgery for NSCLC metastases affords effective local tumor control in approximately 84% of patients. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including GKS can afford patients an extended survival time.     

Patient survival after surgery for osseous metastases from renal cell carcinoma

BACKGROUND: Skeletal metastases from renal cell carcinoma are highly destructive vascular lesions. They pose unique surgical challenges due to the risk of life-threatening hemorrhage and resistance to other treatments. The goal of this retrospective study was to evaluate factors that may affect survival after surgical treatment of metastases of renal cell carcinoma. METHODS: We performed a retrospective review of a series of 295 consecutive patients who had been treated for metastatic renal cell carcinoma at one institution between 1974 and 2004. There were 226 men and sixty-nine women. A total of 368 metastases of renal cell tumors to the extremities and pelvis were treated. The surgical procedures included curettage with cementing and/or internal fixation (214 tumors), en bloc resection (117), closed nailing (twenty-seven), amputation (four), and other measures (six). Overall survival was calculated with Kaplan-Meier analysis. The log-rank test was used to evaluate the effect of different variables on overall survival. RESULTS: The overall patient survival rates at one and five years were 47% and 11%, respectively. The metastatic pattern had a significant effect on the survival rate (p < 0.0001): patients with a solitary bone metastasis had the most favorable overall survival rate. Patients with multiple bone-only metastases had a better survival rate than patients with pulmonary metastases (p = 0.009). A clear-cell histological subtype was also associated with better survival (p < 0.0001). The tumor grade did not predict survival (p = 0.17). Fifteen patients (5%) died within four weeks after surgery. The causes included acute pulmonary failure (seven patients), multiorgan failure (six), cerebrovascular accident (one), and hypercalcemia (one). There were no deaths attributable to intraoperative hemorrhage. Discussion: Survival beyond twelve months is possible for a substantial proportion of patients with metastatic renal cell carcinoma. Patients with a clear-cell histological subtype, bone-only metastases, and a solitary metastasis have superior survival rates. The presence of pulmonary metastases does not predict early death in a reliable manner, and some patients may survive for years with pulmonary and systemic disease. The data are important for surgeons to consider when choosing treatment for these patients. For example, local control of disease and implant stability are important issues for patients with a potential for a long duration of survival.     

UNC-51-like kinase 1 expression in radical nephrectomy specimens as a predicting factor of progression-free survival in patients with metastatic renal cell carcinoma treated with mammalian target of rapamycin inhibitors

BackgroundTo analyze basal expression levels of multiple components in the autophagy pathway in radical nephrectomy specimens from patients with metastatic renal cell carcinoma (mRCC) treated with mammalian target of rapamycin (mTOR) inhibitors, to identify factors predicting susceptibility to these agents.MethodsThis study included 48 consecutive patients undergoing radical nephrectomy, who were diagnosed with mRCC and subsequently treated with either everolimus or temsirolimus. Expression levels of 5 major molecular markers involved in the signaling pathway associated with autophagy, including autophagy-related protein (Atg)5, Atg9, Beclin1, microtubule-associated protein light chain 3, and UNC-51-like kinase 1 (ULK1), were measured by immunohistochemical staining of primary renal cell carcinoma specimens.ResultsDuring the observation period of this study (median = 16.2 mo), 36 patients developed disease progression, with a median progression-free survival (PFS) period of 7.6 months. Of several factors examined, bone metastasis, liver metastasis, and ULK1 expression were shown to have significant effects on the response to mTOR inhibitors. PFS was significantly correlated with the expression level of ULK1 in addition to bone and liver metastases on univariate analysis. Of these significant factors, ULK1 expression and liver metastasis were independently associated with PFS on multivariate analysis.ConclusionsIt may be useful to consider expression levels of potential molecular markers in the autophagy pathway, particularly ULK1, in addition to conventional parameters, when selecting patients with mRCC who are likely to benefit from treatment with mTOR inhibitors.     

Predictors of Survival in Patients With Bone Metastasis of Lung Cancer

The prognosis of patients with bone metastasis from lung cancer has not been well documented. We assessed the survival rates after bone metastasis and prognostic factors in 118 patients with bone metastases from lung cancer. The cumulative survival rates after bone metastasis from lung cancer were 59.9% at 6 months, 31.6% at 1 year, and 11.3% at 2 years. The mean survival was 9.7 months (median, 7.2 months; range, 0.1-74.5 months). A favorable prognosis was more likely in women and patients with adenocarcinoma, solitary bone metastasis, no metastases to the appendicular bone, no pathologic fractures, performance status 1 or less, use of systemic chemotherapy, and use of an epithelial growth factor receptor inhibitor. Analyses of single and multiple variables indicated better prognoses for patients with adenocarcinoma, no evidence of appendicular bone metastases, and treatment with an epithelial growth factor receptor inhibitor. The mean survival period was longer in a small group treated with an epithelial growth factor receptor inhibitor than in the larger untreated group. The data preliminarily suggest treatment with an epithelial growth factor receptor inhibitor may improve survival after bone metastasis.     

Stereotactic radiosurgery for patients with "radioresistant" brain metastases

OBJECTIVE: Our aim was to evaluate the efficacy of stereotactic radiosurgery (SRS) for the treatment of patients with brain metastases that have been determined to be "radioresistant" on the basis of histological examination. METHODS: We reviewed the medical records of 41 consecutive patients who presented with 83 brain metastases from radioresistant primaries and subsequently underwent SRS. All patients were followed until death or for a median of 31 months after SRS. Tumor histologies included renal cell carcinoma (16 patients), melanoma (23 patients), and sarcoma (2 patients). Eighteen patients (44%) had a solitary metastasis, and 23 patients (56%) had multiple metastases. RESULTS: The median overall survival time was 14.2 months after SRS. On the basis of univariate analysis, systemic disease status (P = 0.006) and Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (P = 0.005) were associated with survival. The median survival time was 23.5 months for patients in RPA Class I status and 10.5 months for patients in RPA Class II or III status. There was a trend (P = 0.12) toward improved median survival for patients with renal cell carcinoma (17.8 mo) as compared with patients with melanoma (9.7 mo). Multivariate analysis showed RPA class (P = 0.038) and histological diagnosis of primary tumor (P < 0.001) to be independent predictors for overall survival. In the 35 patients who underwent follow-up imaging, 9 (12%) of 73 tumors recurred locally. In 54% of the patients, distant brain failure (DBF) developed. Whole brain radiotherapy (WBRT) improved local control and decreased DBF, according to the univariate and multivariate analyses. Patients who received adjuvant WBRT in addition to SRS had 6-month actuarial local control of 100% as compared with 85% among those who did not receive WBRT (P = 0.018). Patients who received adjuvant WBRT with SRS had a 6-month actuarial DBF rate of 17%, as compared with a rate of 64% among patients who had SRS alone (P = 0.0027). CONCLUSION: Well-selected patients with brain metastases from radioresistant primary tumors who undergo SRS survive longer than historical controls. RPA Class I status and primary renal cell carcinoma predict longer survival. Adjuvant WBRT improves local control and decreases DBF but does not affect overall survival. Further studies are needed to determine which patients should receive WBRT.