Novel Inflammation-Based Prognostic Score for Predicting Survival in Patients with Metastatic Urothelial Carcinoma.

PURPOSE: We developed a novel inflammation-based model (NPS), which consisted of a neutrophil to lymphocyte ratio (NLR) and platelet count (PC), for assessing the prognostic role in patients with metastatic urothelial carcinoma (UC). MATERIALS AND METHODS: We performed a retrospective analysis of patients with metastatic UC who underwent systemic chemotherapy between January 1997 and December 2014 in Kaohsiung Chang Gung Memorial Hospital. The defined cutoff values for the NLR and PC were 3.0 and 400 × 103/µL, respectively. Patients were scored 1 for either an elevated NLR or PC, and 0 otherwise. The NPS was calculated by summing the scores, ranging from 0 to 2. The primary endpoint was overall survival (OS) by using Kaplan-Meier analysis. Multivariate Cox regression analysis was used to identify the independent prognostic factors for OS. RESULTS: In total, 256 metastatic UC patients were enrolled. Univariate analysis revealed that patients with either a high NLR or PC had a significantly shorter survival rate compared with those with a low NLR (P = .001) or PC (P < .0001). The median OS in patients with NPS 0, 1, and 2 was 19.0, 12.8, and 9.3 months, respectively (P < .0001). Multivariate analysis revealed that NPS, along with the histologic variant, liver metastasis, age, and white cell count, was an independent factor facilitating OS prediction (hazard ratio 1.64, 95% confidence interval 1.20-2.24, P = .002). CONCLUSION: The NLR and PC are independent prognostic factors for OS in patients with metastatic UC. The NPS model has excellent discriminant ability for OS.

Tailored Selection of First-Line Cisplatin-Based Chemotherapy in Patients with Metastatic Urothelial Carcinoma of Bladder.

PURPOSE: Methotrexate, vinblastine, doxorubicin plus cisplatin (MVAC) and gemcitabine plus cisplatin (GC) are both effective first-line chemotherapy. We explore the responsive variables of MVAC and GC for patients with metastatic urothelial carcinoma of bladder (mUCB). MATERIALS AND METHODS: Patients who were initially diagnosed to have mUCB and received MVAC or GC as metastatic first-line chemotherapy between 2000 and 2014 at Kaohsiung Chang Gung Memorial Hospital were reviewed. Totally, 130 patients were enrolled into our study. Univariable Cox proportional hazard models were constructed for OS. Hazard ratio (HR) and 95% confidence intervals (CIs) was also presented. RESULTS: There were 50 patients (38%) in the MVAC group and 80 patients (62%) in the GC group. The median OS was insignificantly different between MVAC and GC groups, accounting for 17.0 and 14.4 months (P = 0.214), respectively. OS of MVAC group was significantly longer with regard to age ≦ 60 years (HR: 0.38, 95% CI: 0.12-0.97, P = 0.036), pure urothelial carcinoma (HR: 0.56, 95% CI: 0.34-0.90, P = 0.015), > 1 metastatic sites (HR: 0.19, 95% CI: 0.08-0.44, P = < 0.001), and neutrophil to lymphocyte ratio > 3(HR: 0.45, 95% CI: 0.25-0.81, P = 0.006), while OS with GC group was significantly longer with regard to variant urothelial carcinoma (HR: 0.56, 95% CI: 0.34-0.90, P = 0.015). CONCLUSIONS: Our study disclosed the predictive factors of different regimen for mUCB. These results have clinical implication for physicians who treat patients with mUCB.

The Prognostic Impact of Histopathological Variants in Patients with Advanced Urothelial Carcinoma.

PURPOSE: This study investigated the prognostic role of histopathological variants in patients with advanced urothelial carcinoma (UC) who were treated with systemic chemotherapy. MATERIALS AND METHODS: We conducted a retrospective analysis of patients with unresectable and/or metastatic UC who underwent systemic chemotherapy between January 1997 and December 2013 in Kaohsiung Chang Gung Memorial Hospital. Histopathological types were categorized as pure UC (PUC) and variants of UC (VUC). The overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier analyses and Cox proportional regression models. RESULTS: A total of 206 patients were enrolled; 53 of the patients (25.7%) had histopathological variants. The most common variant was squamous differentiation (68%). Compared with patients with PUC, patients with VUC significantly exhibited upper urinary tract origin (75% vs 52%, P = .008), chronic renal insufficiency (40% vs 23%, P = .03), and carboplatin-based chemotherapy (28% vs 10%, P = .003). According to univariate analysis, the median OS for PUC patients was significantly higher than that for VUC patients (15.9 vs 11.3 months, P = .007). The median PFS for patients who received first-line chemotherapy was 6.1 and 3.8 months for PUC patients and VUC patients, respectively (P = .004). Multivariate analysis revealed that VUC (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.16-2.40, P = .006), an age ≤ 60 years (HR 0.70, 95% CI 0.49-0.99, P = .045) and presence of visceral metastasis (HR 1.54, 95% CI 1.11-2.13, P = .009) were independent factors facilitating OS prediction. CONCLUSIONS: The presence of histopathological variants indicates poor survival outcomes in patients with metastatic UC. Accordingly, VUC should be integrated into and considered an independent factor in a predictive model of survival.

The use of transdermal fentanyl in cancer pain--a compliance study of outpatients in Taiwan.

The aim of this study is to investigate cancer patients' response and side effects associated with transdermal therapeutic fentanyl (TTS-F), whose pain was hardly controlled by nonweak/weak opioids in Taiwan. From 2005 to 2006, 822 outpatients received TTS-F to collect pain assessment forms and diaries for 4 weeks. Most (78.7%) patients were initially prescribed 25 microg/h TTS-F. Doses were adjusted weekly at clinicians' discretion, according to pain assessment and side effects. Patients receiving 50 microg/h, 75 microg/h, and > 75 microg/h TTS-F had increased from 17.5% to 32.1%, 1.8% to 3.4%, and 1.9% to 2.2%, respectively, by week 2; further small increases were found in weeks 3 and 4. Pain palliation improved from 60.6% during week 1 to 78.6% at week 4. The common adverse effects were nausea/vomiting. Patient's compliance was >90%. This study found that the TTS-F is effective and well tolerated.

Intraarterial Cisplatin and intravenous adriamycin in nonmetastatic osteosarcoma of the extremities: a single institution experience in Taiwan.

BACKGROUND: For nonmetastatic osteosarcoma of the extremities, the optimal treatment now consists of multiagent neoadjuvant and adjuvant chemotherapy and limb-sparing surgical procedures. The degree of tumor necrosis after neoadjuvant chemotherapy is one of the most important prognostic indicators. Intraarterial cisplatin and intravenous adriamycin could achieve a good initial tumor response and convert the response to an ultimate cure. METHODS: Between January 1989 and July 2004, 16 patients with nonmetastatic osteosarcoma of the extremities received intravenous adriamycin and intraarterial cisplatin monthly for 2-5 courses, based on achievement of a maximized angiographic response, followed by limb salvage surgery and then adjuvant intravenous chemotherapy with adriamycin and cisplatin. After resection, if patients had a good response (the extent of tumor necrosis was > or =90%), the same regimen was administered intravenously every three weeks for a total of six courses of chemotherapy. Poor responders (tumor necrosis <90%) were treated with a regimen of high-dose methotrexate with leucovorin rescue (HD-MTX) or ifosfamide, cisplatin, and etoposide (ICE). RESULTS: Patients received an average of four cycles of neoadjuvant intraarterial chemotherapy. Sixteen patients underwent limb-preservation surgery and 12 had >90% tumor necrosis. With an average follow-up of 93.5 months, 8 patients were continuously disease -free, 6 died of disease and 2 had no evidence of disease 112 and 182 months respectively after relapse. The 5-year overall survival rate was 61%. No patient developed clinically detectable cardiac toxicity or ototoxicity after adriamycin and cisplatin administration. Febrile neutropenia occurred infrequently. CONCLUSION: This study shows the effectiveness of treating nonmetastatic osteosarcoma of the extremities with intraarterial cisplatin and intravenous adriamycin infusion in Taiwan. However, the number of patients evaluated and treated in a single hospital was obviously too few to be considered statistically robust and this regimen deserves further testing in a multi-institutional fashion.

Treatment outcomes of patients with AJCC stage IVC nasopharyngeal carcinoma: benefits of primary radiotherapy.

BACKGROUND: There is no agreement on the optimal management of patients initially presenting with metastatic nasopharyngeal carcinoma. This study was performed to investigate the treatment outcomes and to assess whether radiotherapy to the primary tumors has survival benefits. METHODS: From 1993 to 2001, 806 consecutive patients with histology-proven nasopharyngeal carcinoma were registered at our department. Among them, 125 patients had distant metastases and fulfilled the criteria for stage IVC of the 1997 American Joint Committee on Cancer staging system. Tumor histology according to the World Health Organization classification was Type 2 in 67 patients and Type 3 in 58 patients. The most common site of initial metastasis was bone. A total of 28 patients refused any treatment, 39 received chemotherapy alone and 58 had radiotherapy to the primary tumor sites alone. RESULTS: The 1 year overall survival rates were 25, 36 and 48% for patients with no treatment, chemotherapy and radiotherapy, respectively. In multivariate analysis, age of diagnosis and treatment modality were confirmed as independent prognostic factors for overall survival. CONCLUSIONS: Based on our results, radiotherapy to the primary tumor sites could be considered for patients with stage IVC nasopharyngeal carcinoma. A combination of radiotherapy and chemotherapy might have potential survival benefits. Further randomized prospective study is necessary to explore the optimal treatment strategy.

Incidence of ischemic stroke post-chemotherapy: a retrospective review of 10,963 patients.

OBJECTIVE: Vascular occlusion is not an uncommon event in malignancy. However, the frequency of ischemic stroke after chemotherapy has been mentioned only occasionally in clinical studies. A large-scale study is lacking. METHODS: A retrospective study was conducted at Chang Gung Memorial Hospital, Kaohsiung, Taiwan, to analyze the incidence of ischemic stroke post-chemotherapy, further, to evaluate a possible causative relationship between the ischemic stroke and the chemotherapy regimen, the interval between the latest chemotherapy session and onset of ischemic stroke and the survival of patients with ischemic stroke post-chemotherapy. The data were retrieved from the Cancer Database from 1993 to 2004. RESULTS: During this period, a total of 10,963 patients, with malignancies were followed-up for 1 month after chemotherapy, underwent 45,294 chemotherapy sessions. Among this group, there were 15 patients experiencing 16 ischemic strokes within the first month after the latest chemotherapy. Among them, 14 patients were followed-up until death and one patient was lost in follow-up after discharge against medical advice. The incidence of post-chemotherapy ischemic stroke was 0.137% and the frequency of chemotherapy cycles complicated by ischemic stroke was 0.035%. Adenocarcinoma was the most common histological type not only in ischemic stroke (40%) but also in overall patients (36.7%). The hemispheric stroke with middle cerebral artery territory involvement was the most common image finding. Platinum compounds, especially cisplatin, were the most commonly used chemotherapeutic agents for ischemic stroke patients. Twelve (75%) of these 16 ischemic strokes occurred within 10 days of the latest chemotherapy session and 10 (62.5%) occurred after the first cycle of chemotherapy. The median survival after ischemic stroke was 4 weeks. CONCLUSION: Our results provide valuable data on the relationship between malignancy, treated with chemotherapy, and ischemic stroke. The risk of ischemic stroke after chemotherapy is predicted by the use of cisplatin-based chemotherapy not cancer histologic type. Infarction usually involves the territorial subtype, causes obvious neurological disabilities and carries a grave prognosis.

Extrapulmonary small cell carcinoma--a medical center's experience.

BACKGROUND: To review the biologic behavior, therapy and natural courses of patients with extrapulmonary small cell carcinoma (EPSCC) in a medical center. METHODS: We used the computer assisted search for patients diagnosed with EPSCC registered from July 1986 through April 2005. The eligible patients had pathologically proven SCC in sites other than the lung and normal chest radiographs, computed tomography of the chest, sputum cytology, and/or negative bronchoscopic findings. RESULTS: Twenty patients with EPSCC were identified and 12 patients (60%) had limited disease (LD). For the patients with LD receiving systemic chemotherapy, the response rate was 73% (36.5% complete response (CR), 36.5% partial response (PR). However, most of the patients experienced rapid systemic recurrence, with a median disease free survival (DFS) of 8 months. Patients with extensive disease (ED) received mostly etoposide-cisplatin (EP) based chemotherapy, for which the response rate was 50%. The median overall survival (OS) of the patients with LD and ED was 22 months and 3 months. The patients with EPSCC of the head and neck region showed a favorable clinical course, with a median OS of 43 months. Patients with EPSCC of sites other than the head and neck region had aggressive courses with a median OS of 15.5 months. CONCLUSION: Integrated chemoradiotherapy with surgery for patients with LD generates realistic survival results. EP-based chemotherapy should be the current chemotherapy regimen of choice for patients with ED. Patients with EPSCC of sites other than the head and neck region was usually had poor overall outcomes.

Treatment outcomes and late complications of 849 patients with nasopharyngeal carcinoma treated with radiotherapy alone.

PURPOSE: The objective of this study was to describe the treatment outcomes and treatment-related complications of nasopharyngeal carcinoma (NPC) patients treated with radiotherapy alone. METHODS AND MATERIALS: Retrospective analysis was performed on 849 consecutive NPC patients treated between 1983 and 1998 in our institution. Potentially significant patient-related and treatment-related variables were analyzed. Radiation-related complications were recorded. RESULTS: The 5-year overall and disease-free survival rates of these patients were 59% and 52%, respectively. Advanced parapharyngeal space (PPS) invasion showed stronger prognostic value than PPS invasion. Multiple neck lymph node (LN) involvement was demonstrated to be one of the most powerful independent prognostic factors among all LN-related parameters. External beam radiation dose more than 72 Gy was associated with significantly higher incidence of hearing impairment, trismus, and temporal lobe necrosis. CONCLUSIONS: We recommend that the extent of PPS should be clarified and stratified. Multiple neck LN involvement could be integrated into the N-classification in further revisions of the American Joint Committee on Cancer stage. Boost irradiation is not suggested for node-negative necks. For node-positive necks, boost irradiation is indicated and a longer interval between initial and boost irradiation would reduce the incidence of neck fibrosis without compromising the neck control rate.

Retrotracheal thymoma masquerading as esophageal submucosal tumor.

A 42-year-old man presented with a two-year history of progressive dysphagia and hoarseness. Esophagogram and endoscopy revealed submucosal mass effect on the upper esophagus. Computed tomography and magnetic resonance imaging revealed an elongated mass in the retrotracheal region of the lower neck with extension to the posterior mediastinum. Partial tumor resection and histopathological evaluation revealed a WHO type B2 thymoma. Adjuvant radiation and chemotherapy were subsequently administered resulting in complete tumor regression. To our knowledge, this is the first report of ectopic retrotracheal thymoma with clinical and imaging manifestations mimicking those for esophageal submucosal tumor.

Concurrent chemoradiotherapy for unresectable thymic carcinoma.

BACKGROUND: Thymic carcinoma is a rare anterior mediastinal neoplasm. It is more invasive and has a poorer prognosis than ordinary thymoma. Complete curative resection is frequently impossible to achieve because of extensive invasion or metastasis at diagnosis. The role of systemic chemotherapy and the optimal regimen in thymic carcinoma remain uncertain. We report our experience with 16 patients with unresectable thymic carcinoma who underwent concurrent chemoradiotherapy. METHODS: Between July 1989 and July 2003, 29 patients were diagnosed with unresectable thymic carcinoma at our hospital. Sixteen of the 29 patients were treated with concurrent chemoradiotherapy. There were 10 men and 6 women whose ages ranged from 45 to 66 years old. Chemotherapy regimens consisted of either (A) cisplatin plus 5-fluorouracil or (B) doxorubicin, cisplatin, vincristine and cyclophosphamide every 4 weeks for at least 2 cycles. Radiotherapy was given concurrently and ranged from 34.2 to 70 Gy. RESULTS: There were 4 (25.0%) patients with complete responses, 4 (25.0%) with partial responses, 6 (37.5%) with stable disease and 2 (12.5%) with progressive disease. The overall response rate was 50%. The median follow-up was 64 months, and the median survival was 82 months. The overall cumulative survival rates at 1, 2, 3, and 5 years were 93.8%, 81.3%, 74.5%, and 67.7%, respectively. The most common side effects were Grade I/II toxicity, including vomiting, fatigue, and esophagitis. All patients experienced radiation pneumonitis. No life-threatening side effects were noted. CONCLUSIONS: Concurrent chemoradiotherapy seems effective for unresectable thymic carcinoma. Our experience, although preliminary, is encouraging and merits conducting a randomized trial to determine the impact of concurrent chemoradiotherapy on unresectable thymic carcinoma.

Quality of life as a survival predictor for patients with advanced head and neck carcinoma treated with radiotherapy.

BACKGROUND: Accumulating reports suggest that quality of life (QoL) may predict survival in patients with malignant disease. In the current study, the authors investigated if baseline QoL and changes in QoL during treatment were prognostic for patients with advanced head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy. METHODS: The authors studied 102 consecutive new patients with HNSCC treated with primary radiotherapy. The Taiwan Chinese versions of the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and Head and Neck Quality of Life Questionnaire (EORTC QLQ-H&N35) were completed before and during radiotherapy. The Cox proportional hazards models were used to analyze the impact of clinical and QoL variables on survival. RESULTS: Clinical variables that were significant survival predictors included American Joint Committee on Cancer (AJCC) stage, N status, and Karnofsky performance status (KPS) after multivariate analysis. After introducing the QoL variables, baseline fatigue scale and N status emerged as the most significant survival predictors, whereas KPS lost its significance. Changes in the QoL scales during radiotherapy were not significantly correlated with survival. An increase in the baseline fatigue score of 10 points corresponded to a 17% reduction in the likelihood of survival (95% confidence interval: 8-27%). Significant correlations between baseline fatigue scale and KPS, comorbidity, hemoglobin level, AJCC stage, T status, and most QoL scales also were observed. CONCLUSIONS: The data support the correlation of patient reported QoL scales with survival. Pretreatment fatigue level was a significant survival predictor for patients with advanced HNSCC treated with radiotherapy.