Median Survival Duration Of Patients Research Articles

Features of T1 pancreatic cancer and validation of the eighth edition AJCC staging system definition using a Korean-Japanese joint cohort and the SEER database.

Little is known about the features of T1 pancreatic ductal adenocarcinoma (PDAC) and its definition in the eighth edition of the American Joint Committee on Cancer (AJCC) staging system needs validation. The aims were to analyze the clinicopathologic features of T1 PDAC and investigate the validity of its definition. Data from 1506 patients with confirmed T1 PDAC between 2000 and 2019 were collected and analyzed. The results were validated using 3092 T1 PDAC patients from the Surveillance, Epidemiology, and End Results (SEER) database. The median survival duration of patients was 50 months, and the 5-year survival rate was 45.1%. R0 resection was unachievable in 10.0% of patients, the nodal metastasis rate was 40.0%, and recurrence occurred in 55.2%. The current T1 subcategorization was not feasible for PDAC, tumors with extrapancreatic extension (72.8%) had worse outcomes than those without extrapancreatic extension (median survival 107 vs. 39 months, p < .001). Extrapancreatic extension was an independent prognostic factor whereas the current T1 subcategorization was not. The results of this study were reproducible with data from the SEER database. Despite its small size, T1 PDAC displayed aggressive behavior warranting active local and systemic treatment. The subcategorization by the eighth edition of the AJCC staging system was not adequate for PDAC, and better subcategorization methods need to be explored. In addition, the role of extrapancreatic extension in the staging system should be reconsidered.

Clinical characteristics of testicular non-seminomatous germ cell tumor from West China: a 10-year experience.

Clinical characteristics of testicular non-seminomatous germ cell tumor from West China: a 10-year experience.

Features of T1 Pancreatic Cancer and Validation of the Eighth Edition American Joint Committee on Cancer Staging System Definition Using a Korean-Japanese Joint Cohort and the SEER Database

Introduction: The definition of T1 pancreatic cancer was modified in the eighth edition of the American Joint Committee on Cancer staging system. The aims were to analyze the clinicopathologic features of T1 pancreatic ductal adenocarcinoma (PDAC) and investigate the validity of its definition and subcategorization. Methods: Patients confirmed to have T1 PDAC after resection between 2000 and 2019 were identified. Survival analyses and multivariate analyses were performed. The results were validated using T1 PDAC patients in the Surveillance, Epidemiology, and End Results (SEER) database. Results: Data from 1,506 patients were collected. The median survival duration of patients was 50 months, and the 5-year survival rate was 45.1%. R0 resection was unachievable in 10.0% of patients, the nodal metastasis rate was 40.0%, and recurrence occurred in 55.2%. The current T1 subcategorization was not feasible for PDAC (Fig.1), whereas subdividing into two groups with 1.0 cm cut-off was feasible. Tumors with extrapancreatic extension (72.8%) had worse outcomes than those without extrapancreatic extension (median survival 107 vs 39 months, p<0.001). Extrapancreatic extension was an independent prognostic factor whereas the current T1 subcategorization was not (Table.1). Adjuvant treatment resulted in a significant difference in survival and was also a prognostic factor. The results of this study were reproducible with data from 3,092 patients from the SEER database. Conclusion: T1 PDAC displayed aggressive behavior warranting active local and systemic treatment. The subcategorization was not feasible for PDAC, requiring better subcategorization methods. Furthermore, the role of extrapancreatic extension in the staging system should be reconsidered.Tabled 1EP02C-082VariablesUnivariate analysisHazard ratio95% CIp-valueMultivariate analysisHazard ratio95% CIp-valueAge <60 years ≥60 years1.1070.936-1.3110.235Sex Male Female0.8400.726-0.9730.0200.8460.730-0.9810.027Location Head0.0800.631 Body0.8190.687-0.9760.0250.8960.749-1.0700.225 Tail0.8190.625-1.0730.1480.9230.701-1.2160.570 Diffuse0.6410.240-1.7160.3760.8080.299-2.1800.673R status R0<0.001<0.001 R12.1091.696-2.622<0.0011.7411.394-2.173<0.001 R25.1942.577-10.465<0.0013.2631.597-6.6660.001Extrapancreatic extension No Yes1.9011.578-2.289<0.0011.4961.219-1.836<0.001T1 subcategory T1a0.0120.266 T1b1.0330.480-2.2220.9330.8230.380-1.7800.728 T1c1.8000.964-3.3610.0651.1260.591-2.1460.496N category N0<0.001<0.001 N11.6601.417-1.944<0.0011.4781.247-1.751<0.001 N22.9892.368-3.772<0.0012.5862.014-3.321<0.001Lymphovascular invasion Yes<0.0010.309 No0.7040.596-0.831<0.0010.9390.783-1.1260.498 Unknown1.0070.825-1.2300.9441.1280.909-1.4000.274Perineural invasion Yes<0.0010.092 No0.7310.623-0.858<0.0010.8890.748-1.0560.180 Unknown0.7690.514-1.1510.2020.6590.431-1.0090.055Adjuvant treatment Yes0.001<0.001 No1.2431.067-1.4480.0051.4841.266-1.739<0.001 Unknown3.0921.280-7.4700.0122.0070.822-4.8990.126 Open table in a new tab

Whole Brain Radiotherapy Plus Conventional Boost in Non-Small Cell Lung Cancer Patients with Brain Metastasis: A Retrospective Analysis of Overall Survival.

To evaluate the clinical characteristics and treatment outcomes of non-small cell lung cancer (NSCLC) patients with brain metastasis, who were treated by whole brain radiotherapy with a conventional boost at a single institution. A total of 296 patients diagnosed with NSCLC with brain metastasis and referred to our clinic for radiotherapy between 2000 and 2017 were included in this retrospective study. The median age was 60.8 ± 12.1 years, with a range of 21-85 years. The estimated median survival time for all patients was 7.81 ± 0.66 months (95% CI: 6.52-9.11). The one-year survival, two-year survival and three-year survival rates were 18.8%, 5.8% and 2.9%, respectively. The median survival of patients with solitary brain metastasis who received 45 Gy radiotherapy was 14.70 ± 2.80 months (95% CI: 9.20-20.20). These patients had 6 and 12 months survival rates of 65.4% and 42.6%, respectively. The median survival time of patients with solitary brain metastasis who received > 45 Gy radiotherapywas 13.86 ± 2.56 months (95% CI: 8.08-18.02). These patients had 6 and 12 months survival rates of 66.2% and 27.2%, respectively. There was no significant difference between the two groups (p=0.321). The median survival duration of patients under 65 years was 9.65 ± 1.02 months. The median survival time of patients aged 65 years and overwas 5.15 ± 0.51 months. There was a statistically significant difference in the median survival rates between the groups (p < 0.001). Patients with solitary metastasis or single metastases tolerated whole brain radiotherapy with a conventional boost. Although the overall survival rates were numerically better in the high dose RT group, the difference was not statistically significant. Prospective studies with a larger sample size are needed to consolidate our results.

Demographics, management and treatment outcomes of benign and malignant retroperitoneal tumors in Japan.

To show the demographics, type of treatment and clinical outcomes of patients with retroperitoneal tumors in Japan. We carried out a retrospective analysis of patients with retroperitoneal tumors treated between 2000 and 2012 at 12 university hospitals in Japan. Histology was re-evaluated using the 2013 World Health Organization classification. A total of 167 patients were included in the analysis. The number of diagnosed patients increased over the 12-year study period. Liposarcoma and schwannoma were the most common histological types among intermediate/malignant and benign tumors, respectively. The intermediate/malignant tumors were larger and were more frequently found in older people. Surgical resection was the primary treatment for 151 patients. The median survival duration for patients with malignant tumors was 91months, and was significantly shorter than that for patients with benign and intermediate tumors (P<0.01). R2 resection was associated with significantly shorter survival than R0/R1 resection for malignant tumors (P<0.01), but not for intermediate. Grossly complete resection of the recurrent tumors improved survival. The number of patients diagnosed with retroperitoneal tumors increased over time. R2 resection of primary tumors was found to be associated with poor prognosis in malignant tumors, but not in intermediate tumors. Complete surgical resection of recurrent tumors was associated with a better oncological outcome.

Abstract 66: CD99 functional analysis in glioblastoma by RNAseq

Abstract CD99 is a membrane protein expressed in a wide variety of normal tissues and implicated in several cellular physiologic processes, including haematopoietic cell differentiation, proliferation, diapedesis, cell-cell adhesion, migration, apoptosis induction, cellular architecture maintenance and transmembrane protein transport. Additionally, aberrant CD99 expression has been associated with numerous malignancies, including astrocytomas. Amongst astrocytomas of different malignant grades, glioblastoma (GBM) is the most aggressive and common of central nervous system tumors. Despite current multimodal therapies, including surgery, chemotherapy and radiotherapy, the median survival duration of patients is 17 months. We have previously demonstrated increased CD99 expression at mRNA and protein levels in astroctyoma of all malignant grades, with GBM showing the highest levels. Knocking down CD99 expression by siRNA efficiently decreased CD99 at mRNA and protein levels and concurrently decreased the migratory property of two GBM cell lines, U87MG and A172. We subsequently analysed the transcriptoma of both cell lines by RNA-seq in Illumina platform after transfection with siRNA for CD99 and compared to non-target control (NTC). CD99 gene and protein silencing was confirmed in both cell lines. A total of 413 and 340 genes for U87MG and A172, respectively, with expression ≤1.3 (p&amp;lt;0.01, Bejamiini-Hochberg test) in knockdown condition in relation to NTC were detected, and they were analysed according to process networks using Metacore. A total of 129 genes had the expression diminished with CD99 in both cell lines, among them genes coding for proteins involved in migration and cytoskeletal remodelling, as expected. Also, we observed a decreased expression of genes involved in molecular mechanisms of translation control and protein folding regulation, as genes encoding for: subunits of the elongation factor-1 complex (EEF1A and EEF1A1), GTP-binding translation elongation factor (EEF2), several ribosomal proteins (PRPL4, RPL8, RPL15, RPL28, RPL32, RPL37A, RPS2, RPS3, RPS4, RPS6, RPS11 and RPS20), tRNA synthetase proteins (VARS and YARS), and heat shock proteins (HSC70, HSP70, HYOU1 and VCP). Furthermore, expression of MTOR, which encodes a common subunit protein of mTORC1 and mTORC2 complexes, is also downregulated with CD99 knockdown. Altogether, these results open insights for new roles of CD99 in GBM in controlling the regulation of translation, a crucial control of cell growth and proliferation. CD99 could thus be targeted to prevent protein translation in cancer cells. Citation Format: Sueli M. Oba-Shinjo, Lais C. Cardoso, Roseli da Silva, Antonio M. Lerario, Miyuki Uno, Suely S.K. Marie. CD99 functional analysis in glioblastoma by RNAseq. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 66. doi:10.1158/1538-7445.AM2015-66

BMS-536924, an ATP-competitive IGF-1R/IR inhibitor, decreases viability and migration of temozolomide-resistant glioma cells in vitro and suppresses tumor growth in vivo

Glioma is the most common type of primary brain tumor. Despite the combination of surgery, chemotherapy, and radiotherapy, the median survival duration of patients with malignant glioma is still very short. Temozolomide (TMZ) is the primary and most promising therapeutic drug for glioma; however, it is easy to develop acquired resistance during treatment. Activation of receptor tyrosine kinases (RTKs) has been identified to be involved in the acquisition of resistance toward many anticancer drugs. So inhibition of RTKs might be a promising therapeutic strategy for overcoming or attenuating acquired drug resistance. Here, we have investigated the anticancer activities of BMS-536924, an ATP-competitive IGF-1R/IR inhibitor in glioma, especially TMZ-resistant glioma, both in vitro and in vivo. We found that BMS-536924 could effectively reduce viability of both TMZ-sensitive and -resistant glioma cells. BMS-536924 induced dramatic apoptosis in TMZ-resistant cells, and it also dramatically inhibited migration of TMZ-resistant cells. Importantly, BMS-536924 significantly suppressed glioma tumor growth in vivo. This is the first report on anticancer activity of BMS-536924 in glioma. BMS-536924 is a promising compound in the therapy of glioma, especially of TMZ-resistant glioma, which might shed new light on glioma therapy.

Ability of 18-fludeoxyglucose positron emission tomography/CT to detect incidental cancer.

To determine the prevalence and clinical features of pathologically proven incidental cancer (IC) detected by whole-body fluorine-18 fludeoxyglucose ((18)F-FDG) positron emission tomography (PET)/CT, as well as the incidence of false-positive and false-negative results. We retrospectively reviewed reports derived from (18)F-FDG PET/CT images of 3079 consecutive patients with known or suspected malignancies for 3 years. Discrete focal uptake indicating IC was identified from reports as well as pathological or clinical diagnoses, and the clinical courses were investigated. The false-positive result was defined as uptake indicating IC but not pathologically confirmed as malignant during follow-up. The false-negative result was defined as pathologically proven IC detected by another modality at initial clinical work-up or diagnosed during the follow-up period. We found (18)F-FDG uptake indicating IC in 6.7% of all patients, and IC was pathologically proven in 2.2% of all patients. The most common sites were the colon, lung and stomach. The median survival duration of patients with IC was 42 months. The results were false positive in 4.5% of all patients, and the results were false negative in 2.3% of all patients. (18)F-FDG PET/CT is a valuable tool for detecting IC. The rates of false-positive and false-negative results are within acceptable range. This is the first report to describe the survival of patients with IC, and the detailed features of false-negative results at actual clinical settings.

Metastatic breast cancer in patients with schizophrenia

Breast cancer is a major health problem worldwide. The median survival duration for patients with metastatic breast cancer is two to three years. Approximately 1% of populations worldwide have schizophrenia. The manner in which schizophrenic patients fare when diagnosed with metastatic breast carcinoma (MBC) was evaluated. We queried the National Department of Veterans Affairs (DVA) datasets using computer codes for a pre-existing diagnosis of schizophrenia and a later diagnosis of breast carcinoma. Chart-based data concerning the identified subjects were then requested. Previously determined inclusion and exclusion criteria were applied to select evaluable patients from the medical records, prior to extracting demographic details and data concerning the treatment course in each subject. Ten patients had distant metastases at initial diagnosis, while seven developed MBC following prior curative-intent treatment. Two patients refused therapy. Ten did not comply with recommended management. Five harmed or threatened physicians, other caregivers or themselves. Schizophrenic patients with MBC often fail to understand the nature of their illnesses. Often they do not accept palliative treatment, while a number of them do not comply with therapy, once initiated. They often exhibit behaviors that are detrimental to themselves or others. Formal psychiatric consultation is therefore necessary in patients. Several detrimental behaviors may be predicted reliably by history alone.

Endobronchial Mucosa Invasion Predicts Survival in Patients with Small Cell Lung Cancer

BackgroundCurrent staging system for small cell lung cancer (SCLC) categorizes patients into limited- or extensive-stage disease groups according to anatomical localizations. Even so, a wide-range of survival times has been observed among patients in the same staging system. This study aimed to identify whether endobronchial mucosa invasion is an independent predictor for poor survival in patients with SCLC, and to compare the survival time between patients with and without endobronchial mucosa invasion.MethodsWe studied 432 consecutive patients with SCLC based on histological examination of biopsy specimens or on fine-needle aspiration cytology, and received computed tomography and bone scan for staging. All the enrolled patients were assessed for endobronchial mucosa invasion by bronchoscopic and histological examination. Survival days were compared between patients with or without endobronchial mucosa invasion and the predictors of decreased survival days were investigated.Results84% (364/432) of SCLC patients had endobronchial mucosal invasion by cancer cells at initial diagnosis. Endobronchial mucosal involvement (Hazard ratio [HR], 2.01; 95% Confidence Interval [CI], 1.30–3.10), age (HR, 1.04; 95% CI, 1.03–1.06), and extensive stage (HR, 1.39; 95% CI, 1.06–1.84) were independent contributing factors for shorter survival time, while received chemotherapy (HR, 0.32; 95% CI, 0.25–0.42) was an independent contributing factor better outcome. The survival days of SCLC patients with endobronchial involvement were markedly decreased compared with patients without (median 145 vs. 290, p<0.0001). Among SCLC patients of either limited (median 180 vs. 460, p<0.0001) or extensive (median 125 vs. 207, p<0.0001) stages, the median survival duration for patients with endobronchial mucosal invasion was shorter than those with intact endobronchial mucosa, respectively.ConclusionEndobronchial mucosal involvement is an independent prognostic factor for SCLC patients and associated with decreased survival days.

Challenge of Primary Tumor Management in Patients With Stage IV Colorectal Cancer

Optimal first-line therapy of patients who present with primary intact, unresectable stage IV colorectal cancer is controversial. Despite limited data, there are strong biases for either up-front primary tumor resection or for first-line systemic chemotherapy. The argument for up-front primary tumor resection is based on the desire to avoid potential complications of the intact primary tumor (IPT) such as bleeding, obstruction, or tumor perforation. Indeed the concern regarding the risk of primary tumor–related complications during systemic therapy, particularly with bevacizumab, has led both surgical and medical oncologists to advocate primary tumor resection at the time of diagnosis. In fact, the majority of US patients presenting with stage IV disease will still undergo noncurative primary tumor resection. However, during the past decade, several highly active systemic agents, both cytotoxic and biologic, have become available for the treatment of patients with metastatic colorectal cancer. As a result, the median survival duration of patients with unresectable metastatic disease has increased from 9 to 12 months with fluorouracil alone to up to 24 months with sequential modern cytotoxic and biologic treatments. Therefore, it may be generally accepted that, in these patients, systemic chemotherapy with or without primary resection is the essential treatment modality to prolong survival. But these modern agents also have increased activity on the primary tumor and can even induce complete response. Moreover, recent retrospective studies have observed low rates of primary tumor–related complications during treatment in patients with initially asymptomatic disease. Thus the old question of how best to manage the primary tumor continues to be debated. In the article that accompanies this editorial, investigators from the National Surgical Adjuvant Breast and Bowel Project (NSABP) have reported the final results of a phase II prospective, single-arm study of primary systemic chemotherapy with fluorouracil, oxaliplatin (mFOLFOX6) and bevacizumab for patients with asymptomatic primary intact unresectable stage IV colorectal cancer (NSABP C-10). The investigators aimed to directly address the concerns for both primary tumor–related complications associated with first-line systemic therapy in patients with asymptomatic disease and the risk of tumor complications with the use of bevacizumab in this setting. A total of 86 patients from 29 different institutions were evaluated with the primary eligibility criteria being that the treating clinician identified the patient to be asymptomatic with respect to his or her primary tumor. After a median follow-up of 20.7 months, the majority of the patients could be successfully managed nonoperatively without the need for primary tumor intervention, meeting the study’s primary end point. Median overall survival was 19.9 months and the overall rate of major morbidity related to the IPT was 16.3% (95% CI, 7.6% to 25.1%) at 24 months. Thustheinvestigatorsconcludedthatfirst-linecombinationtherapy withmFOLFOX6andbevacizumabdidnotresult inanunacceptablerate of primary tumor–related complications and that noncurative resection of the asymptomatic primary tumor in these patients could be avoided. These findings confirm prior retrospective reports demonstrating low rates of intestinal complications with either fluorouracil-based or more modern systemic chemotherapies. In their prospective evaluation, however, the NSABP investigators have further demonstrated the safety of first-line chemotherapy with bevacizumab in patients with intact but asymptomatic tumors. Indeed, 73.3% of the patients still had not required primary tumor resection at the time of death or last follow-up. This timely report has moved clinical treatment decision making forward and provides prospective evidence that routine noncurative resection may be unnecessary. But this relatively small study also highlights the need to address several other unanswered questions. Establishing that the patient is asymptomatic is the key eligibility criteria for this approach. However, perhaps for pragmatic needs of achieving accrual, “asymptomatic” in this study was broadly defined as having “no evidence of bowel obstruction or perforation, and no active bleeding requiring a transfusion.” Ultimately, it was the treating physician at each one of the 29 different institutions who had to adjudicate whether or not a patient who notes no symptoms, tolerates oral intake, and has bowel movements but is obstructed to the passage of an adult colonoscope (or perhaps some other variation on this theme) is labeled as having asymptomatic disease. This key issue of understanding which patients are eligible for this approach can also influence the true incidence of primary tumor–related morbidity (ie, not all patients with asymptomatic disease are the same). Notably, despite the frequency with which patients with stage IV are identified, and despite the relatively broad eligibility criteria, it took the 29 sites more than 3 years to accrue the 86 eligible patients to the study, perhaps reflecting difficulty on the part of the clinicians for deciding that a patient’s disease was indeed asymptomatic. Another unanswered question is when and how should endoluminal surveillance be performed. No endoluminal surveillance strategy was prespecified, and given the number of investigators in the 29 JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 30 NUMBER 26 SEPTEMBER 1

Survival of Patients with Small Cell Lung Carcinoma in Taiwan

Background: Small cell lung cancer (SCLC) is the most aggressive form of lung cancer. The prognosis for SCLC patients remains unsatisfactory despite advances in chemotherapy. In this study, we sought to clarify the prognosis and treatment patterns of patients with SCLC. Methods: A cohort comprising all patients diagnosed with SCLC between January 2004 and December 2006 was assembled from the Taiwan Cancer Database. Patients were followed up until December 31, 2009, to determine overall survival. Patient survival was estimated using the Kaplan-Meier method, and Cox’s proportional hazard model was used to determine the relationship between prognostic factors and median survival time. Results: Among the 1,684 patients diagnosed with SCLC, 1,215 (72%) were diagnosed with extensive-stage disease and 469 (28%) with limited-stage disease. Most of the patients were male (90%). The median survival duration of patients with limited-stage and extensive-stage SCLC was 10.3 months and 5.6 months, respectively. For limited-stage patients, surgery, chemotherapy, and combined chemotherapy and radiotherapy resulted in better survival than best supportive care (HR 0.20, p < 0.001; HR 0.61, p < 0.001, and HR 0.37, p < 0.001, respectively). For extensive-stage patients, male gender was significantly associated with a poor prognosis (HR 1.45, p < 0.001) and chemotherapy was shown to improve overall survival more effectively than best supportive care (HR 0.37, p < 0.001). Conclusion: For limited-stage SCLC patients, surgery, chemotherapy, and combined chemotherapy and radiotherapy improved survival compared to best supportive care. Extensive-stage SCLC patients benefited more from chemotherapy treatment than from best supportive care.

RNA interference targeting survivin exerts antitumoral effects in vitro and in established glioma xenografts in vivo

Malignant glioma represents the most common primary adult brain tumor in Western industrialized countries. Despite aggressive treatment modalities, the median survival duration for patients with glioblastoma multiforme (GBM), the highest grade malignant glioma, has not improved significantly over past decades. One promising approach to deal with GBM is the inactivation of proteins essential for survival or progression of glioma cells by means of RNA interference (RNAi) techniques. A likely candidate for an RNAi therapy of gliomas is the inhibitor of apoptosis protein survivin. Survivin is involved in 2 main cellular processes–cell division and inhibition of apoptosis. We show here that stable RNAi of survivin induced polyploidy, apoptosis, and impaired proliferation of human U343-MG, U373-MG, H4, and U87-MG cells and of primary glioblastoma cells. Proteome profiler arrays using U373-MG cells identified a novel set of differentially expressed genes upon RNAi-mediated survivin knockdown. In particular, the death receptor TRAIL R2/DR5 was strongly upregulated in survivin-depleted glioma cells, inducing an enhanced cytotoxic response of allogeneic human NK cells. Moreover, an experimental in vivo therapy using polyethylenimine (PEI)/siRNA complexes for survivin knockdown efficiently blocked tumor growth of established subcutaneous U373-MG tumors and enhanced survival of NMRInu/nu mice orthopically transplanted with U87-MG cells. We conclude that survivin is functionally relevant in gliomas and that PEI-mediated exogenous delivery of siRNA targeting survivin is a promising strategy for glioblastoma therapy.

Factors involved in maintaining prolonged functional independence following supratentorial glioblastoma resection

The median survival duration for patients with glioblastoma is approximately 12 months. Maximizing quality of life (QOL) for patients with glioblastoma is a priority. An important, yet understudied, QOL component is functional independence. The aims of this study were to evaluate functional outcomes over time for patients with glioblastoma, as well as identify factors associated with prolonged functional independence. All patients who underwent first-time resection of either a primary (de novo) or secondary (prior lower grade glioma) glioblastoma at a single institution from 1996 to 2006 were retrospectively reviewed. Patients with a Karnofsky Performance Scale (KPS) score ≥ 80 were included. Kaplan-Meier, log-rank, and multivariate proportional hazards regression analyses were used to identify associations (p < 0.05) with functional independence (KPS score ≥ 60) following glioblastoma resection. The median follow-up duration time was 10 months (interquartile range [IQR] 5.6-17.0 months). A patient's preoperative (p = 0.02) and immediate postoperative (within 2 months) functional status was associated with prolonged survival (p < 0.0001). Of the 544 patients in this series, 302 (56%) lost their functional independence at a median of 10 months (IQR 6-16 months). Factors independently associated with prolonged functional independence were: preoperative KPS score ≥ 90 (p = 0.004), preoperative seizures (p = 0.002), primary glioblastoma (p < 0.0001), gross-total resection (p < 0.0001), and temozolomide chemotherapy (p < 0.0001). Factors independently associated with decreased functional independence were: older age (p < 0.0001), coexistent coronary artery disease (p = 0.009), and incurring a new postoperative motor deficit (p = 0.009). Furthermore, a decline in functional status was independently associated with tumor recurrence (p = 0.01). The identification and consideration of these factors associated with prolonged functional outcome (preoperative KPS score ≥ 90, seizures, primary glioblastoma, gross-total resection, temozolomide) and decreased functional outcome (older age, coronary artery disease, new postoperative motor deficit) may help guide treatment strategies aimed at improving QOL for patients with glioblastoma.

Poor Survival Outcome With Moderate and Severe Hypercalcemia in Gynecologic Malignancy Patients

Determine the incidence of hypercalcemia in gynecologic malignancy patients and their survival outcome. Single-institution retrospective clinical study. We used Fisher exact test, Kaplan-Meier survival curves, and Cox proportional hazards model to analyze demographic and clinical data from gynecologic malignancy patients with hypercalcemia who had been treated at The University of Texas M.D. Anderson Cancer Center from September 1997 to August 2006. Of the 5260 gynecologic malignancy patients, 268 had hypercalcemia (5%). Of the 268, 12 were excluded because of hyperparathyroidism or coexisting malignancies; thus, 256 patients were included in the study. Most patients (82%) had mild hypercalcemia. Severity of hypercalcemia was associated with disease stage (P = 0.0019), use of hypercalcemia treatment (P < 0.0001), and survival duration (P < 0.0001). The median survival duration of patients who had not been treated for hypercalcemia was 432 days compared with 106 days in patients who had been treated. The shorter survival duration of treated patients seems to result from their disease status and hypercalcemia severity rather than whether they were treated for hypercalcemia. Moderate and severe hypercalcemia is associated with poorer survival duration in gynecologic malignancy patients. Early detection and treatment of hypercalcemia in these patients may prolong survival. To our knowledge, this is the first study of hypercalcemia in patients with general gynecologic malignancy.

Metastatic disease from spinal chordoma: a 10-year experience

Metastastic lesions have been reported in 5 to 40% of patients with spinal and sacrococcygeal chordoma, but few contemporary series of chordoma metastastic disease exist in the literature. Additionally, the outcome in patients with chordoma-induced metastastic neoplasms remains unclear. The authors performed a retrospective review of the neurosurgery database at the University of Texas M. D. Anderson Cancer Center in Houston to determine the incidence of metastatic disease in a contemporary series of spinal and sacrococcygeal chordoma as well as to determine the outcomes. Thirty-seven patients underwent surgery for spinal and sacrococcygeal chordoma between June 1, 1993, and March 31, 2004. All records were reviewed, and appropriate statistical analyses were used to compare patient data for preoperative characteristics, treatments, and outcomes. The authors identified seven patients (19%) in whom metastatic disease developed; in three the disease had metastasized to the lungs only, in two to the lungs and liver, and in two to distant locations in the spine. There were no significant differences in age, sex, tumor location, or history of radiation treatments between patients with and those without metastases. In cases with local recurrent tumors, metastastic disease was more likely to develop than in those without recurrence (28 compared with 0%, respectively; p = 0.07). In two (12%) of 17 patients who underwent en bloc resection, metastatic disease developed, whereas it developed in five (25%) of 20 patients treated by curettage (p = 0.42). The median time from first surgery to the appearance of metastatic disease, as calculated using the Kaplan-Meier method, was 143.4 months (95% confidence interval [CI] 66.8-219.9). The median survival duration of patients with metastatic disease after the first surgery was 106 months (95% CI 55.7-155.7), and this did not differ significantly from that in patients in whom no metastases developed (p = 0.93). Spinal chordoma metastasized to other locations in 19% of the patients in this series. In patients with local disease recurrence, metastatic lesions are more likely to develop. Metastatic lesions were shown to be aggressive in some cases. Surgery and chemotherapy can play a role in controlling metastatic disease.

Results from a phase III study show that the median survival duration of patients with stage IV M1a melanoma is improved by cancer vaccine HSPPC 96*

Results from a phase III study show that the median survival duration of patients with stage IV M1a melanoma is improved by cancer vaccine HSPPC 96*

Efficacy of Combination Chemotherapy with Paclitaxel and Cisplatin in Patients with Advanced Non-Small Cell Lung Cancer.

To evaluate the efficacy and toxicity of the combination therapy of paclitaxel and cisplatin in advanced, non-small cell, lung cancer patients. Between December 1997 and September 2001, 37 patients with advanced, non-small cell, lung cancer were enrolled in this study. Patients were treated with paclitaxel (135 mg/m2, 24 hr infusion) and cisplatin (75 mg/m2). The treatments were repeated every 4 weeks. Among the 37 patients enrolled, 21 were treated with paclitaxel and cisplatin as a first-line and 16 patients as a second-line. The median age of the patients was 59. In the first-line group, 10 had stage IIIB and 11 had stage IV, non small cell lung cancer. Of 21 patients in first-line treatment group that could be evaluated, objective responses were observed in 6 patients (response rate: 28.6%, CR: 4.8%, PR: 23.8%). The mediansurvival duration for patients was 48 weeks. With the second-line group, 3 patients showed a partial response (response rate: 18.7%) to treatment, with median survival duration of 44 weeks. Grade 3-4 leukopenia was observed in 27.1% of the first-line, and 23.6% in second- line, treatment groups. Combination chemotherapy, with paclitaxel and cisplatin, in non-small cell lung cancer has acceptable toxicities in both first and second-line treatment groups. In terms of efficacy, no superior response was shown for either group. More randomized studies, with a larger group of patients, are required to prove the true efficacy.

ESHAP salvage therapy for relapsed or refractory non-Hodgkin's lymphoma.

The ESHAP regimen, a combination of the chemotherapeutic drugs etoposide, methylprednisolone (solumedrol), high-dose cytarabine (ara-C), and cisplatin, has been shown to be active against refractory or relapsed non-Hodgkin's lymphoma (NHL) in therapeutic trials. We undertook this study to determine whether this regimen would be effective and tolerable in Korean patients. A total of 40 patients with refractory or relapsed NHL (8 indolent and 32 aggressive) were enrolled in this study. The overall response rate was 70% (95% confidence interval; 59.8-89.7%); 22.5% of patients achieved a complete response and 47.5% a partial response. The median survival duration was 12 months (95% confidence interval; 5.9-18.1 months) and the median duration of progression-free survival was 9 months (95% confidence interval; 1.1-16.9 months). The median survival duration of patients with relapsed NHL was longer than that of patients with refractory lymphoma (15 months vs 4 months, p=0.02). Myelosuppression was the most frequent complication and treatment-related mortality was noted in two patients. These results suggest that the ESHAP regimen is effective in patients with relapsed NHL who have a sensitive disease. The role of ESHAP chemotherapy in discriminating patients who are more likely to benefit from a subsequent transplant should be evaluated in the future.

Prognostic factors in pancreatic carcinoma: serum LDH levels predict survival in metastatic disease.

In this study, our aim was to investigate the impact of various prognostic factors on survival in patients with pancreatic carcinoma. The group consisted of 127 cases with adenocarcinoma histologically. The patients had a median age of 58 years, and 81 (64%) were male. The median survival time of the whole group was 7 months, and the 4-year survival rate was 18%. The median survival duration of the patients without metastases was 8 months, and the survival rate at 1 year was 37.5% and 7.2% at 5 years. It was associated with improved survival compared with the cases with metastatic disease (p < 0.0001). In univariate analysis, decreased performance status (p = 0.0009) and unresectability of tumor (p < 0.0001) were associated with poor outcome. However, only surgery was found to be a statistically significant parameter in multivariate analysis (p = 0.002). The median survival duration of patients with metastases was 5 months, and the 1-year survival rate was 10%. Age younger than 60 years (p = 0.04), decreased serum hemoglobin levels (p = 0.04), and elevated lactic dehydrogenase (LDH) levels (p = 0.0001) were associated with a significantly shorter survival rate. In the Cox model, a high serum LDH level was the only independent unfavorable prognostic factor (p = 0.001). In conclusion, surgical intervention in the group without metastases and serum LDH levels in the group with metastases were the most important prognostic factors influencing survival. Pretreatment serum LDH determinations may provide a useful means of stratifying patient populations when comparing treatment programs for advanced pancreatic cancer.