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Reliability of Conclusions from Early Analyses of Real-World Data for Newly Approved Drugs in Advanced Gastric Cancer in the United States
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Collecting duct carcinoma (CDC) of the kidney is an aggressive disease with a poor prognosis, accountings for less than 1% of all renal cancers. To date, no standard therapy for CDC has been established. The aim of this study is an investigation of clinicopathologic findings of CDC and correlation of the disease status with a prognosis.
From 1996 to 2009, 35 patients with CDC were treated at eight medical centers. The diagnosis of CDC was made based on nephrectomy in 27 cases and renal biopsy in eight cases.
Median PFS and OS for all patients were 5.8 months (95% CI 3.5 to 9.2) and 54.4 months (95% CI 0 to 109.2), respectively. The OS of patients with Stages I-III was 69.9 months (95% CI 54.0 to 85.8), while that of patients with Stage IV was 8.6 months (95% CI 0 to 23.3), which showed a statistically significant difference (p=0.01). In addition, among patients with Stage IV, the OS of patients who received a palliative treatment (immunotherapy, chemotherapy, or targeted therapy) was 18.4 months, which was higher than the OS of patients without treatment of 4.5 months.
CDC is a highly aggressive form of renal cell carcinoma. Despite most of the treatments, PFS and OS were short, however, there were some long-term survivors, therefore, conduct of additional research on the predictive markers of the several clinical, pathological differences and their treatments will be necessary.
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We investigated the clinicopathologic information of patients with gastric cancer with multiple primary cancers (GC-MPC) of three or more sites.
Between 1995 and 2009, 105,908 patients were diagnosed with malignancy at Severance Hospital, Yonsei University Health System. Of these, 113 (0.1%) patients with MPC of three or more sites were registered, and 41 (36.3%) of these were GC-MPC. We retrospectively reviewed the clinical data and overall survival using the medical records of these 41 GC-MPC patients. We defined synchronous cancers as those occurring within 6 months of the first primary cancer, while metachronous cancers were defined as those occurring more than 6 months later.
Patients with metachronous GC-MPC were more likely to be female (p=0.003) and young than patients with synchronous GC-MPC (p=0.013). The most common cancer sites for metachronous GC-MPC patients were the colorectum, thyroid, lung, kidney and breast, while those for synchronous GC-MPC were the head and neck, esophagus, lung, and kidney. Metachronous GC-MPC demonstrated significantly better overall survival than synchronous GC-MPC, with median overall survival durations of 4.7 and 14.8 years, respectively, and 10-year overall survival rates of 48.2% and 80.7%, respectively (p<0.001).
Multiplicity of primary malignancies itself does not seem to indicate a poor prognosis. The early detection of additional primary malignancies will enable proper management with curative intent.
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The proper dose and schedule of sunitinib have yet to be established for patients with metastatic renal cell carcinoma (RCC) on hemodialysis. We reviewed two patients with metastatic RCC on hemodialysis who had been treated with sunitinib in Yonsei Cancer Center, Yonsei University College of Medicine. Fifty milligrams of sunitinib was administered intermittently after each hemodialysis session (3 or 4 times a week). Overall responses were partial response in both cases. Progression-free survivals were 16 and 6 months, respectively, at the time of reporting (April 2010). Both subjects tolerated the treatment.
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With their prolonged survival and malnutrition, cancer patients, and especially gastrointestinal (GI) tract cancer patients, can develop Wernicke's encephalopathy (WE). The aim of this study is to remind physicians of the importance of WE and prompt management in patients with GI tract cancer.
This study is a retrospective review of 2 cases of WE in advanced gastric cancer (AGC) patients, and we review the literature for cases of GI tract cancer related to WE.
A 48-year-old female with AGC presented dizziness and diplopia for 5 days and a 20 kg weight loss. Neurologic exam showed nystagmus and gaze disturbance. Her symptoms improved after daily parenteral injection of thiamine 100 mg for 17 days. A 58-year-old female with AGC presented with sudden disorientation, confusion and 15 kg weight loss. Neurologic exam showed gaze limitation and mild ataxia. Despite daily parenteral injection of thiamine 100 mg for 4 days, she died 5 days after the onset of neurologic symptoms. Combining the cases noted in the literature review with our 2 cases, the 7 gastric cancer cases and 2 colorectal cancer cases related to WE showed similar clinical characteristics; 1) a history of long-period malnutrition and weight loss, 2) relatively typical neurologic signs and symptoms and 3) specific magnetic resonance image findings. Except for 2 patients who had irreversible neurologic symptoms, the other 7 patients were improved with prompt thiamine treatment.
It is important to consider WE in GI tract cancer patients with acute neurologic symptoms and who are in a state of malnutrition. Thiamine should be given as soon as possible when WE is suspected.
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Patients with advanced gastric adenocarcinoma who were untreated or had only received first-line chemotherapy, were treated with either paclitaxel (PFL; 175 mg/m2) or docetaxel (DFL; 75 mg/m2) on day 1, followed by a bolus of LV (20 mg/m2 days 1~3) and a 24-hour infusion of 5-FU (1,000 mg/m2 days 1~3) every 3 weeks. The primary endpoint was overall response rate (ORR) and the secondary endpoint included survival and toxicity.
Sixty-six patients received DFL (first-line [n=38]; and second-line [n=28]) and 60 patients received PFL (first-line [n=37]; and second-line [n=23]). The ORRs were not significantly different between the 2 groups (DFL, 26%; PFL, 38%). With a median follow-up of 9.5 months, the progression free survival was 5.2 months (95% confidence interval [CI], 4.2~6.5 months) for DFL and 3.3 months (95% CI, 1.3~5.5 months) for PFL (p=0.17). The overall survival was also comparable between the patients who received DFL and PFL (10.0 months [95% CI, 7.2~12.5 months] and 13.9 months [95% CI, 10.9~19.2 months], respectively; p=0.37). The most frequent grade 3~4 adverse event was neutropenia (DFL, 71%; PFL, 62%). DFL and PFL had different non-hematologic toxicities; specifically, grade ≥3 mucositis (5%) and diarrhea (3%) were common in DFL, while nausea/vomiting (15%) and peripheral neuropathy (5%) were common in PFL.
Thus, the two taxanes had similar efficacy in the treatment of advanced gastric cancer, but different toxicity profiles. Prospective comparative studies are required to further clarify the role of taxanes in the treatment of advanced gastric cancer.
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Ezrin is a membrane cytoskeletal linker protein and it is known to be associated with metastasis of primary osteosarcoma. The aim of this study is to determine the relationship between an ezrin expression and several key clinical parameters and to elucidate its potential prognostic value for patients with osteosarcoma.
Seventy patients with histologically confirmed osteosarcoma and who had no distant metastasis were enrolled between 1995 and 2005 at Yonsei Cancer Center, Severance Hospital, Korea. The clinical parameters were retrospectively reviewed and immunohistochemical staining (IHC) for ezrin was performed using the surgically resected specimens.
Of the 70 tumor specimens, 39 (55.7%) revealed an ezrin expression. More of an osteoblastic histology and an elevated initial ALP level were observed in the ezrin positive patients than in the ezrin negative patients (p=0.008 and 0.001, respectively). The proportion of patients who favorably responded to neoadjuvant chemotherapy (≥90% necrosis) was significantly higher in the group of ezrin positive patients than that in the group of ezrin negative patient (72.2% vs 45.2%, respectively, p=0.024). The ezrin positive patients showed more frequent recurrence than did the ezrin negative patients (64.1% vs 35.5%, respectively, p=0.017). The patients with an ezrin expression also demonstrated poorer survival than did those patients without ezrin expression (5-year EFS: 31.7% vs 61.3%, respectively, p=0.023, 5-year OS: 53.4% vs 71.0%, respectively, p=0.022). When comparing EFS according to both an ezrin expression and chemoresponsiveness, there were trends that the ezrin negative/chemoresponsive group showed the best 5-year EFS (71.4%), followed by the ezrin negative/chemoresistant group (52.9%), the ezrin positive/chemoresponsive group (38.1%) and the ezrin positive/chemoresistant group (13.6%). These trends were statistically significant (p=0.036).
The expression of ezrin by IHC staining was found in 55.7% of the patients with metastasis-free osteosarcoma. Immunoreactivity to ezrin is a negative prognostic factor for survival for the patients suffering with osteosarcoma. Identifying an ezrin expression might offer a valuable piece of information when treating patients with primary osteosarcoma.
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The aim of this study was to determine the prognosis of pN3 stage gastric cancer patients after they have undergone curative resection, and we also wanted to identify the prognostic factors according to the clinico-pathologic features.
Between January 2000 and December 2004, we retrospectively reviewed the medical records of the patients with histologically confirmed pN3 stage gastric cancer. They underwent both gastrectomy and lymphadenectomy with a curative aim. We categorized the pN3 stage patients into 2 groups; one with pN3 only (pN3M0) and the other with pN3 combined with M1 stage (pN3M1) that included peritoneal seeding, hepatic metastasis or para-aortic LN metastasis.
Out of 467 patients with stage IV gastric adenocarcinoma who received surgery, 260 patients underwent curative resection and they were pathologically staged as N3. Among these 260 patients, 78 patients were classified as the pN3/M1 stage. For all the patients, the median follow-up period was 19 months (range: 1~108 months) and the median overall survival time was 16.2 months (95% CI, 14.1~18.3%). The 5-year survival rate of the pN3/M0 group was significantly higher than that of the pN3/M1 group (12.6% vs. 2.6%, respectively, p<0.0001). The identified predictor for a worse prognosis was an advanced T4 stage (HR: 3.38, 95% CI, 1.4~8.3, p=0.008) for the pN3 patients.
The survival for the pN3 gastric cancer patients after curative gastrectomy was significantly longer in the pN3/M0 group as compared to that of the pN3/M1 group. An advanced T stage was a predictor for a poor prognosis for the pN3 patients. Therefore, diverse treatment strategies for these heterogeneous pN3 gastric cancer patients are needed for improving their survival.
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