The Cancer Journal最新文献

{"title":"Image‐Guided Radiofrequency Ablation of Spinal Tumors: Preliminary Experience with an Expandable Array Electrode","authors":"D. Grönemeyer, S. Schirp, A. Gevargez","doi":"10.1097/00130404-200201000-00007","DOIUrl":"https://doi.org/10.1097/00130404-200201000-00007","url":null,"abstract":"PURPOSEMetastases to the spine are a challenging problem. Percutaneous, image-guided tumor ablation with a thermal energy source, such as radiofrequency, has received increasing attention as a promising technique for the treatment of focal malignant disease.We used radiofrequency ablation for patients with unresectable, osteolytic spine metastases under computed tomographic and fluoroscopic guidance. The purpose of this study was to determine the feasibility, effectiveness, and safety of radiofrequency ablation as a palliative procedure to reduce pain and back pain-related disability in patients with vertebral and paravertebral spine tumors who were not able to benefit from radiotherapy, chemotherapy, or surgery. PATIENTS AND METHODSBetween November 1999 and January 2001, 10 patients with unresectable spine metastases were treated with radiofrequency ablation. For the ablation we used a 50-W radiofrequency generator that is connected to an expandable electrode catheter (RITA Medical System Inc., Mountain View, CA). The mean patient age was 64.4 years. Metastases were ablated in the thoracic spine, the lumbar spine, and/or the sacral bone. Tumordiameter ranged from 1.5 to 9 cm. Combined computed tomographic and fluoroscopic guidance was used to guide the procedure.Operations were carried out without heavy sedation with the patient under local anesthesia only. The thermal lesion was produced by applying temperatures of 50° to 120°C for 8–12 minutes. Vertebroplasty was performed in four patients by use of 3 to 5.5 mL of polymethyl methacrylate. Therapy outcome was documented by magnet resonance imaging. Before the therapy and on follow-up of an average of 5.8 months, pain was assessed with the help of the Visual Analogue Scale. Back pain-related disability was measured with the Hannover Functional Ability Questionnaire. Neurologic and health status were documented on the Frankel score and the Karnofsky index. RESULTSAt follow-up, 9 of 10 patients reported reduced pain (Visual Analogue Scale). In patients who experienced pain relief, there was an average relative pain reduction of 74.4%. Back pain-related disability was reduced by an average of 27%. Neurologic function was preserved in nine patients and improved in one. General health was stabilized in six patients, slightly increased (by 10%-20%) in two patients, significantly enhanced (by 50%) in one patient, and slightly reduced in one patient. No complications were reported. In the treated region, magnetic resonance imaging showed no further tumor growth after the therapy. DISCUSSIONRadiofrequency ablation was successfully performed in all 10 patients. Needles were placed accurately under image guidance, and a controlled lesion was created. Pain- and back pain-related disability was clearly reduced, and neurologic function was preserved or stabilized. When confirmed by further investigation, this therapy may be a new option for patients with unresectable spine tumors that do not respond to radiot","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90538697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascular Endothelial Growth Factor Enhances Endothelial Cell Survival and Tumor Radioresistance","authors":"V. Gupta, N. Jaskowiak, M. Beckett, H. Mauceri, Jeremy Grunstein, R. Johnson, D. Calvin, E. Nodzenski, M. Pejovic, D. Kufe, M. Posner, R. Weichselbaum","doi":"10.1097/00130404-200201000-00009","DOIUrl":"https://doi.org/10.1097/00130404-200201000-00009","url":null,"abstract":"PURPOSEVascular endothelial growth factor (VEGF) is an important mediator of endothelial cell proliferation and survival. The purpose of the present studies was to investigate the role of VEGF in the tumor response to ionizing radiation. METHODSTwo ras-transformed murinefibrosarcoma cell lines, VEGF+/+ and VEGF−/− were exposed to ionizing radiation (0, 1, 3, 5, 7 or 9 Gy) in vitro, and clonogenic survival was determined. VEGF+/+ and VEGF-- xenografts were generated in athymic nude mice and then treated with ionizing radiation (ten 5-Gy fractions = 50 Gy). Mean fractional tumor volume was used to evaluate treatment efficacy. To determine whether VEGF enhances tumor radioresistance by targeting endothelial cells, we performed clonogenic survival assays with human umbilical vein endothelial cells. Surviving fractions were calculated after treatment with ionizing radiation (5 Gy) and recombinant hVEGF165 (0, 1, 10, and 100 ng/mL). To determine whether VEGF neutralization enhances tumor radio-sensitivity, we employed anti-VEGF165 monoclonal antibody to treat human tumor xenografts. Tumors were exposed to ionizing radiation (four 5-Gy fractions = 20 Gy) and treated with anti-VEGF antibody (0, 5, and 25 μg/kg in four intraperitoneal doses). Mean fractional tumor volume was used to evaluate treatment efficacy. To elucidate the molecular mechanism contributing to the observed anti-VEGF/ionizing radiation interaction, we exposed human umbilical vein endothelial cells to ionizing radiation (5 Gy) in the presence of anti-VEGF antibody (1 μg/mL). Sodium dodecyl sulfate polyacrylamide gel electrophoresis of cell lysates was probed for mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK1/MEK2). RESULTSThe in vitro radiosensitivities of the VEGF+/+ and VEGF−/− clones were equivalent (Do = 146 vs 149). However, the VEGF+/+ xenografts were more resistant to the cytotoxic effects of ionizing radiation than the VEGF−/− xenografts. VEGF+/+ xenografts demonstrated a faster doubling time (4.5 vs 6.0 days) and a shorter growth delay (15 vs 23 days) than VEGF−/− xenografts. The surviving fraction of human umbilical vein endothelial cells after exposure to ionizing radiation was significantly enhanced in the presence of VEGF (6.4% vs 12.5%). Western blot analysis demonstrated that stimulation of MAPK and MEK1/MEK2 was abrogated after exposure to anti-VEGF antibody. DISCUSSIONThese findings represent the first genetic evidence that factors other than inherent tumor cell radiosensitivity are important determinants of radiocurability. Antitumor strategies targeting VEGF and other endothelial cell survival mechanisms may be used to enhance the cytotoxic effects of radiotherapy.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79221898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High‐Dose‐Rate Remote Afterloading Intracavitary Br achy therapy for the Treatment of Extrahepatic Biliary Duct Carcinoma","authors":"Jiade J. Lu, Y. Bains, M. Abdel-Wahab, A. H. Brandon, A. Wolfson, W. Raub, C. M. Wilkinson, A. Markoe","doi":"10.1097/00130404-200201000-00013","DOIUrl":"https://doi.org/10.1097/00130404-200201000-00013","url":null,"abstract":"PURPOSEThe purpose of this study was to determine whether a dose response exists for extrahepatic bile duct carcinoma (EBDC) when treated with increasingly higher radiation doses delivered via a combination of external beam radiation (EBRT) and high dose rate intracavitary brachytherapy (HDRIB). To establish the best tolerated dose of HDRIB. METHODS AND MATERIALSEighteen patients with pathologically proven, locoregional but unresectable or incompletely resected EBDC were studied from 1991–1998 in this phase I/II trial. All patients received EBRT, delivered via megavoltage photons at standard fractionation schedules, for a total dose of 45 Gy. The HDRIB was delivered using the nucleotron HDR remote afterloading unit with a 10 Ci Ir192 source. Each treatment of HDRIB delivered 7 Gy at 1 cm depth. The first group of eight patients received one treatment of HDRIB (Group 1, total dose = 52 Gy). The second group of six patients received two weekly treatments (Group 2, total dose = 59 Gy). The last group of four patients received three weekly treatments of HDRIB (Group 3, total dose = 66 Gy). HDRIB was delivered once weekly concomitant with the EBRT. Acute adverse reactions were evaluated after for each group of patients before escalating to the next higher dose level of HDRIB. RESULTSThe median follow up time for all 18 patients was 15 months. The median survival for all 18 patients was 12.2 months (range 2 to 79.6 months). Overall two-year survival was 27.8%. Three patients (16.7%) had survival of more than 5 years. Dose response is suggested by the median survival of the three groups (9, 12.2, and 20.3 months for Group 1, 2, and 3, respectively), although this did not reach statistical significance. Complete or partial response (>50% reduction in tumor size) was seen in 25% of patients receiving total of 52 Gy compared to 80% of patients (5 patients in Group 2 and 3 patients in Group 3) receiving greater than 59 Gy (P = 0.05). No patients developed Grade 4 complications. One patient in Group 2 developed Grade 3 toxicity after second treatment of HDRIB. CONCLUSIONHigh dose rate brachytherapy of 21 Gy in three divided weekly treatments, plus 45 Gy of external beam radiation is well tolerated. A dose response is shown with significant increase of PR and CR rate for dose >59 Gy. This modality of treatment appears to be safe and effective for inoperable extrahepatic biliary duct carcinoma.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87497567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Evidence‐Based Analysis of the Management of Localized Prostate Cancer","authors":"I. Abdalla, A. Basu, S. Hellman","doi":"10.1097/00130404-200201000-00008","DOIUrl":"https://doi.org/10.1097/00130404-200201000-00008","url":null,"abstract":"PURPOSEPatients with localized prostate cancer and their doctors face complex trade-offs when deciding on treatment. In this study, we modify the “number needed to treat” method to compare radical prostatectomy with radiotherapy. METHODSA MEDLINE search was performed to identify all studies of radical protatectomy or radiotherapy for prostate cancer. Number needed to treat formulas were modified to account for not only survival but also for complications and their utilities. RESULTSThe unadjusted number needed to treat value for overall survival was 6 favoring prostatectomy (six patients have to undergo prostatectomy to have one more 10-year survivor than if they had undergone radiotherapy). Radiotherapy patients were 4 years older than prostatectomy patients. Because overall survival is strongly linked to patients' age and overall health, the numbers needed to treat for disease-specific and distant metastasis-free survival were analyzed to minimize patient selection bias. The unadjusted number needed to treat values for disease-specific and distant metastasis-free survival were 14 and 18, respectively. When number needed to treat is adjusted for complications and utilities, its value for overall survival is 14, disease-specific survival is -25, and distant metastasis free survival is -22, these last two favoring radiotherapy. CONCLUSIONSUtility-adjusted numbers needed to treat for prostatectomy and radiotherapy are greatly influenced by the likelihood of complications and the utility loss ascribed to them. When literature-reported values are used, radiotherapy is superior, but the differences in outcomes are small. With prostate-specific antigen screening and refined treatment methods, these values will change, and the modified number needed to treat can be used to evaluate, report and compare results. The consequences of treatment in terms of both survival and quality of life determine patient choice and physician recommendations.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88118743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Total Gangliosides and TA90‐IC Levels: Novel Immunologic Markers in Colorectal Cancer","authors":"C. Perez, M. Ravindranath, Rishab K. Gupta, R. Tollenaar, C. J. van de Velde, T. Wood, D. Soh, D. Morton, A. Bilchik","doi":"10.1097/00130404-200201000-00010","DOIUrl":"https://doi.org/10.1097/00130404-200201000-00010","url":null,"abstract":"BACKGROUNDBecause of the challenge in defining prognostic markers predictive of recurrence or progression, carcinoembryonic antigen (CEA) remains the most frequently used marker in colorectal cancer, despite its low sensitivity. We hypothesized that TA90-IC status and serum ganglioside levels might be useful markers and might be of prognostic significance in colorectal cancer. METHODSSerum samples from 68 patients undergoing surgical treatment for histologically proven colorectal cancer were analyzed for the presence of CEA, serum gangliosides, and TA90-IC. Forty-one patients had node-negative disease, whereas 27 patients had limited metastatic disease. The intent was curative resection, even for patients with metastatic disease. Cryopreserved serum specimens were analyzed in a blinded fashion for total serum ganglioside levels (by an assay that detects lipid-associated sialic acids), for CEA, and for TA90-IC (by a murine monoclonal antibody-based enzyme-linked immunosorbent assay). A positive value for TA90-IC levels was defined as an optical density (OD) of more than 0.410 at 405 nm. RESULTSSerum ganglioside levels were elevated more frequently than CEA concentrations (84% vs 44%). The combination of serum ganglioside and CEA values was more sensitive (88%) than CEA value alone (44%) in identifying patients with early-stage colorectal cancer. TA90-IC levels were elevated more frequently than CEA concentrations (56% vs 32%). The combination of TA90-IC and CEA values was more sensitive (72%) than CEA value alone (32%) in identifying patients with advanced-stage colorectal cancer. At an enzyme-linked immunosorbent assay cutoff level of 0.410, 15 (56%) patients had positive TA90-IC values. Fourteen patients alive with residual disease had a median OD TA90-IC level of 0.879, and only three patients had levels below the OD cutoff value of 0.410. Thirteen patients with no evidence of disease had a median level of 0.277, and only four patients had OD levels > 0.410. TA90-IC was significantly higher in the alive with residual disease patients than those rendered no evidence of disease (P = 0.02). CONCLUSIONSWe speculate that a multiple-marker analysis that combines CEA values with serum ganglioside and TA90-IC values may be more sensitive than CEA value alone for detecting colorectal cancer. The potential prognostic significance of TA90-IC status in advanced disease warrants further investigation.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76248418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose/Volume Relationship of Late Rectal Bleeding After External Beam Radiotherapy for Localized Prostate Cancer: Absolute or Relative Rectal Volume?","authors":"P. Kupelian, C. Reddy, T. Carlson, T. Willoughby","doi":"10.1097/00130404-200201000-00011","DOIUrl":"https://doi.org/10.1097/00130404-200201000-00011","url":null,"abstract":"PURPOSEThe purpose of this study was to analyze predictors of late rectal bleeding after external-beam radiotherapy for localized prostate cancer, with a focus on the volume of rectum irradiated. MATERIALS AND METHODSOne hundred twenty-eight patients were treated with external-beam radiotherapy at the Cleveland Clinic Foundation between January 1998 and June 1999. Conformal radiotherapy (CRT) was used to deliver 78 Gy at 2 Gy per fraction in 76 cases, and short-course intensity-modulated radiotherapy (SCIM-RT)was used to deliver 70 Gy at 2.5 Gy per fraction in 52 cases. All contours were determined by one physician. The rectum was outlined from 1 cm above the target structures to 1 cm below the target structures. The entire volume of the rectum, along with the outer rectal wall, was included. All cases had detailed planning parameters that specifically determined the rectal volume receiving the prescription dose (VrPr), that is, 78 Gy for CRT and 70 Gy for SCIM-RT, and the percent of rectal volume receiving the prescription dose (%VrPr). The RTOG scales were used to evaluate late toxicity. The median follow-up was 24 months for all cases (range, 3–34 months), 21 months for SCIM-RT cases (range, 11–26 months), and 28 months for CRT cases (range, 3–34 months). RESULTSTo date, five patients have had grade 1 late rectal toxicity (one CRT case and four SCIM-RT cases), one patient had grade 2 late rectal toxicity (CRT), and three patients had grade 3 late rectal toxicity (all CRT cases). Because of the low number of events, the analysis was performed with all patients experiencing rectal bleeding grouped together. The actuarial rectal bleeding rates at 18 and 24 months were 6% and 8%, respectively. The actuarial rectal bleeding rates at 24 months were identical (8%) for both SCIM-RT and CRT. A multivariate analysis of the following parameters was performed to determine independent predictors of rectal bleeding: age (continuous variable), race (Caucasian vs African American), coverage of seminal vesicles (yes vs no), adjuvant androgen deprivation (yes vs no), technique (CRT vs SCIM-RT), Radiation Therapy Oncology Group acute rectal toxicity score (continuous variable), VrPr (continuous variable in cubic centimeters), and %VrPr (continuous variable). Only the VrPr (cubic centimeter) was an independent predictor of rectal bleeding; %VrPr was not. With different cut-off levels being used, a VrPr of 15 cm3 was significant on univariate analysis; the actuarial rectal bleeding rates at 24 months for patients with a VrPr ≤ 15 cm3 versus a VrPr > 15 cm3 were 5% versus 22%, respectively. CONCLUSIONIn our study sample, which included both conformal and intensity-modulated radiotherapy patients, the volume of rectum receiving the prescribed radiation dose (the equivalent of 78 Gy) was an independent predictor of late rectal bleeding. The percent of rectal volume receiving the full dose was not. Using actual volume rather than percent volume also avoids the depende","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84194943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}