Pub Date : 2015-11-01DOI: 10.1097/PPO.0000000000000153
M. Davila, C. Sauter, R. Brentjens
Abstract Recently, immunotherapy for cancer has begun to garner traction with encouraging results in a number of malignancies. Included within this arena has been the genetic engineering of autologous T cells with chimeric antigen receptors (CARs) against tumor target. The majority of this experience has included the use of CAR T cells directed against CD19 for B-cell hematologic malignancies. The most striking efficacy to date with CAR T cells directed against CD19 has been in relapsed and refractory B-cell acute lymphoblastic leukemia, with the overwhelming majority of patients experiencing complete remissions. In addition, single-center and largely early-phase studies have demonstrated responses in patients with varying histologic findings of relapsed and refractory B-cell non-Hodgkin lymphoma. The favorable response rates seen with this technology have been tempered by the high risk of toxicity, particularly in the form of cytokine-release syndrome and neurotoxicity. Agents such as tocilizumab and corticosteroids have been used to treat these toxicities. The current state of the science includes strategies to circumvent and treat toxicity, manufacturing, and study of later-generation CAR constructs with the intention of improving efficacy and development of CARs against other tumor targets for both hematologic and solid tumor malignancies. The observation of an early efficacy ensures further integration and development of this modality into future immunotherapeutic strategies for various cancers.
{"title":"CD19-Targeted T Cells for Hematologic Malignancies: Clinical Experience to Date","authors":"M. Davila, C. Sauter, R. Brentjens","doi":"10.1097/PPO.0000000000000153","DOIUrl":"https://doi.org/10.1097/PPO.0000000000000153","url":null,"abstract":"Abstract Recently, immunotherapy for cancer has begun to garner traction with encouraging results in a number of malignancies. Included within this arena has been the genetic engineering of autologous T cells with chimeric antigen receptors (CARs) against tumor target. The majority of this experience has included the use of CAR T cells directed against CD19 for B-cell hematologic malignancies. The most striking efficacy to date with CAR T cells directed against CD19 has been in relapsed and refractory B-cell acute lymphoblastic leukemia, with the overwhelming majority of patients experiencing complete remissions. In addition, single-center and largely early-phase studies have demonstrated responses in patients with varying histologic findings of relapsed and refractory B-cell non-Hodgkin lymphoma. The favorable response rates seen with this technology have been tempered by the high risk of toxicity, particularly in the form of cytokine-release syndrome and neurotoxicity. Agents such as tocilizumab and corticosteroids have been used to treat these toxicities. The current state of the science includes strategies to circumvent and treat toxicity, manufacturing, and study of later-generation CAR constructs with the intention of improving efficacy and development of CARs against other tumor targets for both hematologic and solid tumor malignancies. The observation of an early efficacy ensures further integration and development of this modality into future immunotherapeutic strategies for various cancers.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"54 1","pages":"470–474"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87513076","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}
Dyspnea, defined as uncomfortable or labored breathing, is a common and often devastating cause of distress for patients and their caregivers with advanced cancer and other life-threatening illnesses. The mechanism by which dyspnea develops is not fully understood, but it involves integration of the central respiratory complex with the sensory (perceptual) cortex. The gold standard of diagnosis is patient self-report. Careful assessment should be undertaken to identify reversible existing causes. Systemic opioids are the first-line therapy for symptomatic management, along with other general comfort measures (positioning, cool air, calming environment). Medical or surgical management can be directed toward underlying causes. Advanced care planning should include discussions concerning the burdens and benefits of medical/surgical management of underlying causes of dyspnea to more effectively direct goals of care. This article reviews current literature on dyspnea, with a focus on items published since 2000.
{"title":"Dyspnea","authors":"C. M. Williams","doi":"10.32388/bwkik4","DOIUrl":"https://doi.org/10.32388/bwkik4","url":null,"abstract":"Dyspnea, defined as uncomfortable or labored breathing, is a common and often devastating cause of distress for patients and their caregivers with advanced cancer and other life-threatening illnesses. The mechanism by which dyspnea develops is not fully understood, but it involves integration of the central respiratory complex with the sensory (perceptual) cortex. The gold standard of diagnosis is patient self-report. Careful assessment should be undertaken to identify reversible existing causes. Systemic opioids are the first-line therapy for symptomatic management, along with other general comfort measures (positioning, cool air, calming environment). Medical or surgical management can be directed toward underlying causes. Advanced care planning should include discussions concerning the burdens and benefits of medical/surgical management of underlying causes of dyspnea to more effectively direct goals of care. This article reviews current literature on dyspnea, with a focus on items published since 2000.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"28 1","pages":"365–373"},"PeriodicalIF":0.0,"publicationDate":"2006-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77649114","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}
Pub Date : 2004-09-01DOI: 10.1016/J.IJROBP.2004.07.279
K. Raj, E. S. Evans, R. Prosnitz, B. Quaranta, P. Hardenbergh, D. Hollis, K. Light, L. Marks
{"title":"Is There an Increased Risk of Local Recurrence Under the Heart Block in Patients with Left‐Sided Breast Cancer?","authors":"K. Raj, E. S. Evans, R. Prosnitz, B. Quaranta, P. Hardenbergh, D. Hollis, K. Light, L. Marks","doi":"10.1016/J.IJROBP.2004.07.279","DOIUrl":"https://doi.org/10.1016/J.IJROBP.2004.07.279","url":null,"abstract":"","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"20 1","pages":"309–317"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73733077","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}
Pub Date : 2002-07-01DOI: 10.1097/00130404-200207000-00011
D. Labow, J. Buell, A. Yoshida, S. Rosen, M. Posner
BACKGROUNDResection of colorectal hepatic metastases is an accepted treatment modality for stage IV colorectal cancer. Concurrent or sequential pulmonary metastasectomy continues to be a controversial strategy. We analyzed factors that predicted pulmonary recurrence in patients with resected hepatic metastases and examined the efficacy of these combined interventions in the treatment of metastatic colorectal cancer. METHODSA retrospective review of a database of patients who underwent resection of colorectal hepatic metastases was performed to identify patients who either had synchronous pulmonary metastases (defined as pulmonary recurrence at the time of or within 3 months of hepatic metastasectomy) or subsequently experienced pulmonary metastases. Patient demographics, operative interventions, and overall survival were analyzed. Statistical methods included unpaired Student's t-test, actuarial survival and log-rank analysis. RESULTSTwenty-one patients (19%) had pulmonary metastases after hepatic resection, of which 12/21(57%) underwent pulmonary resection. No differences were observed between the resection group, the nine patients with pulmonary metastases who did not undergo resection, and the 87 patients without pulmonary metastases with regard to age, sex, race, or extent of hepatic metastases. When comparing the resected versus the unresected pulmonary recurrences, the disease-free interval from hepatic resection to detection of pulmonary metastases was 21 ± 20 months (range, 3–72 months) versus 16 ± 8 months (range, 4–25 months), respectively. All patients with pulmonary recurrence who underwent pulmonary metastasectomy had unilateral disease. Seven of 12 (58%) underwent wedge/segmental resections, and the remaining five (42%) required lobectomy in order to obtain a complete resection. Four patients who underwent pulmonary resection had multiple lung metastases (two to four lesions), and eight had isolated metastasis. There were no perioperative deaths in the pulmonary metastasectomy group. Contraindications to pulmonary resection included extensive pulmonary disease and concurrent extrapulmonary disease. A survival benefit was noted at 3 years for the resected versus the unresected group (60% vs 31%). Survival was no different between the resected pulmonary recurrence patients and the resected hepatic metastases only patients (60% vs 54%). CONCLUSIONSPulmonary metastasectomy can be performed safely and effectively in patients with recurrent disease after hepatic resection for colorectal metastases. Prolonged survival can be achieved with resection of isolated pulmonary recurrence after hepatic resection for colorectal cancer. Further studies that delineate selection criteria for pulmonary resection of colorectal metastases are warranted.
背景:结直肠癌肝转移灶切除术是IV期结直肠癌的一种公认的治疗方式。同时或顺序肺转移切除术仍然是一个有争议的策略。我们分析了预测肝转移切除患者肺复发的因素，并检查了这些联合干预治疗转移性结直肠癌的疗效。方法回顾性分析接受结直肠肝转移切除术的患者数据库，以确定同步肺转移(定义为在肝转移切除术时或术后3个月内肺复发)或随后发生肺转移的患者。分析患者人口统计学、手术干预和总生存率。统计方法包括未配对学生t检验、精算生存和log-rank分析。结果肝切除术后发生肺转移的患者21例(19%)，其中12/21例(57%)行肺切除术。在切除组、未切除的9例肺转移患者和87例无肺转移患者之间，在年龄、性别、种族或肝转移程度方面没有观察到差异。当比较切除与未切除的肺部复发时，从肝切除到发现肺转移的无病间隔分别为21±20个月(范围，3-72个月)和16±8个月(范围，4-25个月)。所有接受肺转移切除术的肺复发患者均为单侧疾病。12例患者中有7例(58%)接受了楔形/节段性切除术，其余5例(42%)需要肺叶切除术以获得完全切除术。接受肺切除术的4例患者有多发肺转移(2至4个病灶)，8例有孤立转移。肺转移切除术组围手术期无死亡病例。肺切除术的禁忌症包括广泛的肺部疾病和并发的肺外疾病。与未切除组相比，切除组在3年生存率上有明显提高(60% vs 31%)。切除肺复发患者和仅切除肝转移患者的生存率无差异(60% vs 54%)。结论对结直肠癌肝切除术后复发的患者行肺转移切除术是安全有效的。结直肠癌肝切除术后孤立性肺复发切除可延长生存期。进一步研究确定肺切除结肠转移瘤的选择标准是有必要的。
{"title":"Isolated Pulmonary Recurrence After Resection of Colorectal Hepatic Metastases—Is Resection Indicated?","authors":"D. Labow, J. Buell, A. Yoshida, S. Rosen, M. Posner","doi":"10.1097/00130404-200207000-00011","DOIUrl":"https://doi.org/10.1097/00130404-200207000-00011","url":null,"abstract":"BACKGROUNDResection of colorectal hepatic metastases is an accepted treatment modality for stage IV colorectal cancer. Concurrent or sequential pulmonary metastasectomy continues to be a controversial strategy. We analyzed factors that predicted pulmonary recurrence in patients with resected hepatic metastases and examined the efficacy of these combined interventions in the treatment of metastatic colorectal cancer. METHODSA retrospective review of a database of patients who underwent resection of colorectal hepatic metastases was performed to identify patients who either had synchronous pulmonary metastases (defined as pulmonary recurrence at the time of or within 3 months of hepatic metastasectomy) or subsequently experienced pulmonary metastases. Patient demographics, operative interventions, and overall survival were analyzed. Statistical methods included unpaired Student's t-test, actuarial survival and log-rank analysis. RESULTSTwenty-one patients (19%) had pulmonary metastases after hepatic resection, of which 12/21(57%) underwent pulmonary resection. No differences were observed between the resection group, the nine patients with pulmonary metastases who did not undergo resection, and the 87 patients without pulmonary metastases with regard to age, sex, race, or extent of hepatic metastases. When comparing the resected versus the unresected pulmonary recurrences, the disease-free interval from hepatic resection to detection of pulmonary metastases was 21 ± 20 months (range, 3–72 months) versus 16 ± 8 months (range, 4–25 months), respectively. All patients with pulmonary recurrence who underwent pulmonary metastasectomy had unilateral disease. Seven of 12 (58%) underwent wedge/segmental resections, and the remaining five (42%) required lobectomy in order to obtain a complete resection. Four patients who underwent pulmonary resection had multiple lung metastases (two to four lesions), and eight had isolated metastasis. There were no perioperative deaths in the pulmonary metastasectomy group. Contraindications to pulmonary resection included extensive pulmonary disease and concurrent extrapulmonary disease. A survival benefit was noted at 3 years for the resected versus the unresected group (60% vs 31%). Survival was no different between the resected pulmonary recurrence patients and the resected hepatic metastases only patients (60% vs 54%). CONCLUSIONSPulmonary metastasectomy can be performed safely and effectively in patients with recurrent disease after hepatic resection for colorectal metastases. Prolonged survival can be achieved with resection of isolated pulmonary recurrence after hepatic resection for colorectal cancer. Further studies that delineate selection criteria for pulmonary resection of colorectal metastases are warranted.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"69 1","pages":"342–347"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88979756","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}
Pub Date : 2002-07-01DOI: 10.1097/00130404-200207000-00007
J. Hainsworth, A. Meluch, Suzanne McClurkan, J. Gray, S. Stroup, H. Burris, D. Yardley, J. Bradof, K. Yost, James K. Ellis, F. Greco
PURPOSEThe purpose of this study was to evaluate the feasibility, toxicity, and efficacy of a novel combined-modality treatment for patients with locally advanced squamous carcinoma of the head and neck. PATIENTS AND METHODSIn this multicenter, community-based phase II study, 123 previously untreated patients with locally advanced squamous carcinoma of the head and neck received 6 weeks of induction chemotherapy followed by concurrent high-dose radiation therapy and weekly chemotherapy. Induction chemotherapy included paclitaxel (200 mg/m2, 1-hour i.v. infusion) on days 1 and 22, carboplatin (AUC 6.0 i.v.) on days 1 and 22, and 5-fluorouracil (225 mg/m2 per day, 24-hour continuous i.v. infusion) on days 1–43. After 1 week without therapy, radiation therapy, 1.8 Gy/day, 5 days weekly, to a total dose of 68.4 Gy, was administered to the primary site and the bilateral cervical lymph nodes. During radiation therapy, patients also received six weekly doses of paclitaxel (50 mg/m2, 1-hour i.v. infusion) and carboplatin (AUC 1.0 i.v). After completion of therapy, patients were restaged with computed tomographic and endoscopic examination; patients in complete remission were followed up without further treatment. RESULTSOne hundred twenty-three patients (74% with stage IV disease) entered this trial, and 111 patients (90%) completed the entire treatment course. Seventy of 116 evaluable patients (60%; 95% CI, 51%-69%) had a clinical complete response to treatment. After a median follow-up of 24 months, the 2-and 3-year actuarial survivals were 66% and 51%, respectively. Local toxicity was moderately severe during combined-modality therapy; however, xerostomia has been the only frequent chronic toxicity of this program. CONCLUSIONSThis novel combined-modality treatment program, containing paclitaxel and avoiding the use of cisplatin, is feasible, is highly active, and can be administered with acceptable toxicity in a community-based setting. Aggressive nutritional support should be considered in patients receiving this regimen, to improve acute palliation and to maximize the delivery of combined-modality therapy. Further evaluation of this treatment program is warranted. Incorporation of various novel biologic agents, particularly the epidermal growth factor receptor antagonists, may further improve efficacy.
{"title":"Induction Paclitaxel, Carboplatin, and Infusional 5‐FU Followed by Concurrent Radiation Therapy and Weekly Paclitaxel/Carboplatin in the Treatment of Locally Advanced Head and Neck Cancer: A Phase II Trial of the Minnie Pearl Cancer Research Network","authors":"J. Hainsworth, A. Meluch, Suzanne McClurkan, J. Gray, S. Stroup, H. Burris, D. Yardley, J. Bradof, K. Yost, James K. Ellis, F. Greco","doi":"10.1097/00130404-200207000-00007","DOIUrl":"https://doi.org/10.1097/00130404-200207000-00007","url":null,"abstract":"PURPOSEThe purpose of this study was to evaluate the feasibility, toxicity, and efficacy of a novel combined-modality treatment for patients with locally advanced squamous carcinoma of the head and neck. PATIENTS AND METHODSIn this multicenter, community-based phase II study, 123 previously untreated patients with locally advanced squamous carcinoma of the head and neck received 6 weeks of induction chemotherapy followed by concurrent high-dose radiation therapy and weekly chemotherapy. Induction chemotherapy included paclitaxel (200 mg/m2, 1-hour i.v. infusion) on days 1 and 22, carboplatin (AUC 6.0 i.v.) on days 1 and 22, and 5-fluorouracil (225 mg/m2 per day, 24-hour continuous i.v. infusion) on days 1–43. After 1 week without therapy, radiation therapy, 1.8 Gy/day, 5 days weekly, to a total dose of 68.4 Gy, was administered to the primary site and the bilateral cervical lymph nodes. During radiation therapy, patients also received six weekly doses of paclitaxel (50 mg/m2, 1-hour i.v. infusion) and carboplatin (AUC 1.0 i.v). After completion of therapy, patients were restaged with computed tomographic and endoscopic examination; patients in complete remission were followed up without further treatment. RESULTSOne hundred twenty-three patients (74% with stage IV disease) entered this trial, and 111 patients (90%) completed the entire treatment course. Seventy of 116 evaluable patients (60%; 95% CI, 51%-69%) had a clinical complete response to treatment. After a median follow-up of 24 months, the 2-and 3-year actuarial survivals were 66% and 51%, respectively. Local toxicity was moderately severe during combined-modality therapy; however, xerostomia has been the only frequent chronic toxicity of this program. CONCLUSIONSThis novel combined-modality treatment program, containing paclitaxel and avoiding the use of cisplatin, is feasible, is highly active, and can be administered with acceptable toxicity in a community-based setting. Aggressive nutritional support should be considered in patients receiving this regimen, to improve acute palliation and to maximize the delivery of combined-modality therapy. Further evaluation of this treatment program is warranted. Incorporation of various novel biologic agents, particularly the epidermal growth factor receptor antagonists, may further improve efficacy.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"53 1","pages":"311–321"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87071774","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}
Pub Date : 2002-07-01DOI: 10.1097/00130404-200207000-00010
J. Krieger, B. L. Stanford, E. Ballard, I. Rabinowitz
PURPOSEA pilot taxane test-dose policy was developed and implemented to determine whether the severity of patient hypersensitivity reaction and drug waste would be reduced. PATIENTS AND METHODSData from 206 eligible cancer patients undergoing first-dose taxane chemotherapy were analyzed. The severity of hypersensitivity reactions before and after the implementation of taxane test dose was graded (scale 1–4) and analyzed for statistical differences between groups. Average drug wastage was calculated before and after program initiation. RESULTSTwenty-two of 206 patients (10.7%) experienced a hypersensitivity reaction. The mean hypersensitivity reaction severity for reacting patients who did not receive a test dose (N = 12) was 3.3, and for those who were given a test dose (N = 10), it was 1.5. Only one of five patients who experienced a hypersensitivity reaction that required hospitalization was from the test-dose group. The value of drug alone wasted before test-dose utilization was about $1794 per reacting patient, and the use of taxane test doses saved approximately $1784 per reacting individual. This represented more than a $178 savings for every patient receiving a taxane for the first time. These figures do not include resuscitation, hospital, and other subsequent other costs associated with morbidity. CONCLUSIONSImplementation of a taxane test-dose policy significantly reduced hypersensitivity reaction severity, drug wastage, and hospitalizations.
{"title":"Implementation and Results of a Test Dose Program with Taxanes","authors":"J. Krieger, B. L. Stanford, E. Ballard, I. Rabinowitz","doi":"10.1097/00130404-200207000-00010","DOIUrl":"https://doi.org/10.1097/00130404-200207000-00010","url":null,"abstract":"PURPOSEA pilot taxane test-dose policy was developed and implemented to determine whether the severity of patient hypersensitivity reaction and drug waste would be reduced. PATIENTS AND METHODSData from 206 eligible cancer patients undergoing first-dose taxane chemotherapy were analyzed. The severity of hypersensitivity reactions before and after the implementation of taxane test dose was graded (scale 1–4) and analyzed for statistical differences between groups. Average drug wastage was calculated before and after program initiation. RESULTSTwenty-two of 206 patients (10.7%) experienced a hypersensitivity reaction. The mean hypersensitivity reaction severity for reacting patients who did not receive a test dose (N = 12) was 3.3, and for those who were given a test dose (N = 10), it was 1.5. Only one of five patients who experienced a hypersensitivity reaction that required hospitalization was from the test-dose group. The value of drug alone wasted before test-dose utilization was about $1794 per reacting patient, and the use of taxane test doses saved approximately $1784 per reacting individual. This represented more than a $178 savings for every patient receiving a taxane for the first time. These figures do not include resuscitation, hospital, and other subsequent other costs associated with morbidity. CONCLUSIONSImplementation of a taxane test-dose policy significantly reduced hypersensitivity reaction severity, drug wastage, and hospitalizations.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"75 1","pages":"337–341"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80949557","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}
Pub Date : 2002-07-01DOI: 10.1097/00130404-200207000-00008
G. Merrick, W. Butler, J. Lief, R. Galbreath, E. Adamovich
PURPOSEThe purpose of this article is to report the 5-year biochemical disease-free outcome for hormone-naive patients with high-risk disease who underwent permanent prostate brachytherapy. Multiple clinical and treatment parameters were also evaluated to determine whether any of these influence biochemical outcome. MATERIALS AND METHODSSixty-six hormone-naïve patients underwent transperineal ultrasound-guided permanent prostate brachytherapy with generous periprostatic margins by use of either 103Pd or 125I for high-risk prostate cancer from April 1995 to October 1999. High-risk patients presented with two or three of the following risk factors: Gleason score ≥ 7, prostate-specific antigen ≥ 10 ng/mL, and clinical stage ≥ T2b, 1997 AJCC. No patient underwent pathological lymph node staging. Only one patient was implanted with monotherapy, whereas 65 patients received supplemental external-beam radiation therapy before a prostate brachytherapy boost. The median patient age was 69 years (range, 50–81 years). No patient was lost to follow-up. The mean follow-up and median follow-up were 53.2 ± 14.9 months and 53.7 months, respectively (range, 19.8–79.7 months). Follow-up was calculated from the day of implantation. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiology and Oncology consensus definition. Clinical parameters evaluated for biochemical disease-free survival included patient age, clinical stage, Gleason score, and pretreatment prostate-specific antigen. Treatment parameters included use of supplemental external-beam radiation therapy and choice of isotope. RESULTSThe 5-year actuarial biochemical disease-free survival rate was 79.9%. In multivariate analysis, preimplantation prostate-specific antigen (P = 0.008) was the only clinical or treatment parameter that predicted for biochemical failure. The mean and median posttreatment prostate-specific antigen levels were 0.13 ± 0.22 ng/mL and < 0.1 ng/mL, respectively. DISCUSSIONAt a median follow-up of 53.7 months, hormone-naive patients with high-risk disease who undergo permanent prostate brachytherapy have a high probability of 5-year biochemical disease-free survival and an apparent plateau on the biochemical disease-free survival curve.
{"title":"Biochemical Outcome for Hormone‐Naïve Patients with High‐Risk Prostate Cancer Managed with Permanent Interstitial Br achy therapy and Supplemental External‐Beam Radiation","authors":"G. Merrick, W. Butler, J. Lief, R. Galbreath, E. Adamovich","doi":"10.1097/00130404-200207000-00008","DOIUrl":"https://doi.org/10.1097/00130404-200207000-00008","url":null,"abstract":"PURPOSEThe purpose of this article is to report the 5-year biochemical disease-free outcome for hormone-naive patients with high-risk disease who underwent permanent prostate brachytherapy. Multiple clinical and treatment parameters were also evaluated to determine whether any of these influence biochemical outcome. MATERIALS AND METHODSSixty-six hormone-naïve patients underwent transperineal ultrasound-guided permanent prostate brachytherapy with generous periprostatic margins by use of either 103Pd or 125I for high-risk prostate cancer from April 1995 to October 1999. High-risk patients presented with two or three of the following risk factors: Gleason score ≥ 7, prostate-specific antigen ≥ 10 ng/mL, and clinical stage ≥ T2b, 1997 AJCC. No patient underwent pathological lymph node staging. Only one patient was implanted with monotherapy, whereas 65 patients received supplemental external-beam radiation therapy before a prostate brachytherapy boost. The median patient age was 69 years (range, 50–81 years). No patient was lost to follow-up. The mean follow-up and median follow-up were 53.2 ± 14.9 months and 53.7 months, respectively (range, 19.8–79.7 months). Follow-up was calculated from the day of implantation. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiology and Oncology consensus definition. Clinical parameters evaluated for biochemical disease-free survival included patient age, clinical stage, Gleason score, and pretreatment prostate-specific antigen. Treatment parameters included use of supplemental external-beam radiation therapy and choice of isotope. RESULTSThe 5-year actuarial biochemical disease-free survival rate was 79.9%. In multivariate analysis, preimplantation prostate-specific antigen (P = 0.008) was the only clinical or treatment parameter that predicted for biochemical failure. The mean and median posttreatment prostate-specific antigen levels were 0.13 ± 0.22 ng/mL and < 0.1 ng/mL, respectively. DISCUSSIONAt a median follow-up of 53.7 months, hormone-naive patients with high-risk disease who undergo permanent prostate brachytherapy have a high probability of 5-year biochemical disease-free survival and an apparent plateau on the biochemical disease-free survival curve.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"25 1","pages":"322–327"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82851086","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}
Pub Date : 2002-07-01DOI: 10.1097/00130404-200207000-00006
Robbin Hsiung, Weizhu Zhu, G. Klein, Wenyi Qin, A. Rosenberg, P. Park, E. Rosato, E. Sauter
PURPOSEThe angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial growth factor are important in malignant breast epithelial growth. Nipple aspirate fluid (NAF) is a physiologic fluid collected noninvasively that contains proteins secreted by the breast ductal epithelium and may contain markers of breast cancer. The purpose of this study was to determine whether high concentrations of bFGF and vascular endothelial growth factor in NAF would be associated with in situ and invasive breast cancer, and whether prostate-specific antigen, a marker in NAF associated with breast cancer, would improve our ability to determine which subjects had the disease. METHODSBoth bivariate and multivariate analyses were performed to determine the effects of race, menopausal status, bFGF concentration, and prostate-specific antigen on cancer risk. Bivariate analysis was also performed to determine the relationship between vascular endothelial growth factor concentration and cancer risk. RESULTSMean NAF bFGF levels were higher in women with breast cancer than in those without (19.2 vs 1.74 ng/g). Vascular endothelial growth factor was not associated with breast cancer. Race and menopausal status did not significantly affect the relationship between bFGF and cancer risk. bFGF, race, and menopausal status were each independent predictors of breast cancer, with bFGF being the most important. With knowledge of all three variables, the model was 89.9% sensitive and 69.0% specific in predicting which women had breast cancer. Adding prostate-specific antigen increased the sensitivity to 90.9% and the specificity to 83.3%. In subjects with NAF bFGF > 150 ng/g and prostate-specific antigen < 100 ng/g, 94.1% (32/34) of subjects had cancer. For women with NAF prostate-specific antigen > 100 ng/ g and bFGF < 150 ng/g, 90.5% were cancer free. CONCLUSIONSbFGF concentration in NAF is directly associated with breast cancer, regardless of race and menopausal status. NAF bFGF may prove helpful in the early detection of breast cancer.
{"title":"High Basic Fibroblast Growth Factor Levels in Nipple Aspirate Fluid Are Correlated with Breast Cancer","authors":"Robbin Hsiung, Weizhu Zhu, G. Klein, Wenyi Qin, A. Rosenberg, P. Park, E. Rosato, E. Sauter","doi":"10.1097/00130404-200207000-00006","DOIUrl":"https://doi.org/10.1097/00130404-200207000-00006","url":null,"abstract":"PURPOSEThe angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial growth factor are important in malignant breast epithelial growth. Nipple aspirate fluid (NAF) is a physiologic fluid collected noninvasively that contains proteins secreted by the breast ductal epithelium and may contain markers of breast cancer. The purpose of this study was to determine whether high concentrations of bFGF and vascular endothelial growth factor in NAF would be associated with in situ and invasive breast cancer, and whether prostate-specific antigen, a marker in NAF associated with breast cancer, would improve our ability to determine which subjects had the disease. METHODSBoth bivariate and multivariate analyses were performed to determine the effects of race, menopausal status, bFGF concentration, and prostate-specific antigen on cancer risk. Bivariate analysis was also performed to determine the relationship between vascular endothelial growth factor concentration and cancer risk. RESULTSMean NAF bFGF levels were higher in women with breast cancer than in those without (19.2 vs 1.74 ng/g). Vascular endothelial growth factor was not associated with breast cancer. Race and menopausal status did not significantly affect the relationship between bFGF and cancer risk. bFGF, race, and menopausal status were each independent predictors of breast cancer, with bFGF being the most important. With knowledge of all three variables, the model was 89.9% sensitive and 69.0% specific in predicting which women had breast cancer. Adding prostate-specific antigen increased the sensitivity to 90.9% and the specificity to 83.3%. In subjects with NAF bFGF > 150 ng/g and prostate-specific antigen < 100 ng/g, 94.1% (32/34) of subjects had cancer. For women with NAF prostate-specific antigen > 100 ng/ g and bFGF < 150 ng/g, 90.5% were cancer free. CONCLUSIONSbFGF concentration in NAF is directly associated with breast cancer, regardless of race and menopausal status. NAF bFGF may prove helpful in the early detection of breast cancer.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"46 1","pages":"303–310"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91219602","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}
Pub Date : 2002-05-01DOI: 10.1097/00130404-200205000-00009
M. Mohiuddin, M. Kudrimoti, W. Regine, P. Mcgrath, N. Hanna, W. John
PURPOSEPreclinical studies have demonstrated significant synergistic tumor cell death when gemcitabine is combined with radiation therapy. The optimal mode for concomitant delivery of drug and radiation therapy remains to be determined. A phase I/II study was undertaken to establish the maximum tolerated dose of infusional gemcitabine when combined with radiation therapy in advanced gastrointestinal malignancies and to assess the response to treatment. MATERIALS AND METHODSTwenty-five patients with advanced or recurrent gastrointestinal malignancy were entered in this dose-escalation study. The initial dose of gemcitabine was 50 mg/m2 as a 24-hour continuous intravenous infusion given weekly × 3 with concurrent radiation therapy. The patients were given a week off chemotherapy after the third injection. The radiation therapy was continued during that week. Gemcitabine was thereafter resumed weekly for another 3 weeks or until the patient completed the radiation therapy (whichever was earlier). Five patients were treated at each dose level. The dose of the drug was escalated in increments of 50 mg/m2 if the toxicity was acceptable at the previous level until the maximum tolerated dose was established. Thirteen patients with advanced unresectable colorectal cancer and 12 patients with advanced unresectable pancreaticobiliary cancers were enrolled on the study. Radiation was delivered at 180 cGy/fraction to a total dose of 4000 cGy ± boost. Because toxicity was severe at the 150 mg/m2 dose level, three additional patients were entered at this dose level. The dose was then dropped to 125 mg/m2, and five more patients were entered at this dose level. Two additional patients were then added in orderto assess toxicity. Patient follow-up ranged from 4 to 22 months, and the median was 8 months. RESULTSAll patients were evaluable for toxicity. The doses of 50 and 100 mg/m2 were well tolerated, but at 150 mg/m2, six of eight patients experienced grade 3 or greater toxicity. The dose was de-escalated to 125 mg/m2, and three of seven patients showed grade 3 diarrhea and weight loss. Clinical tumor response was evaluable in 20 patients. Ten patients had a complete clinical response (50%), five patients had a partial response (25%), three patients had no response, and two patients had progression of disease. No patients experienced late toxicities related to either gemcitabine administration or radiation therapy. Twelve patients are currently alive. CONCLUSIONBased on these results, it appears that the maximum tolerated dose for weekly 24-hour infusion of gemcitabine combined with radiation therapy is 100 mg/m2. Gemcitabine appears to be a potent radiation sensitizer, and when combined with radiation therapy, it has shown encouraging tumor responses. In this study, we found an overall response rate of 75% in patients with locally advanced stage of disease. Further evaluation of gemcitabine at 100 mg/m2 is being undertaken in preparation for a confirmatory multi
{"title":"Concurrent Infusional Gemcitabine and Radiation in the Treatment of Advanced Unresectable GI Malignancy: A Phase I Study","authors":"M. Mohiuddin, M. Kudrimoti, W. Regine, P. Mcgrath, N. Hanna, W. John","doi":"10.1097/00130404-200205000-00009","DOIUrl":"https://doi.org/10.1097/00130404-200205000-00009","url":null,"abstract":"PURPOSEPreclinical studies have demonstrated significant synergistic tumor cell death when gemcitabine is combined with radiation therapy. The optimal mode for concomitant delivery of drug and radiation therapy remains to be determined. A phase I/II study was undertaken to establish the maximum tolerated dose of infusional gemcitabine when combined with radiation therapy in advanced gastrointestinal malignancies and to assess the response to treatment. MATERIALS AND METHODSTwenty-five patients with advanced or recurrent gastrointestinal malignancy were entered in this dose-escalation study. The initial dose of gemcitabine was 50 mg/m2 as a 24-hour continuous intravenous infusion given weekly × 3 with concurrent radiation therapy. The patients were given a week off chemotherapy after the third injection. The radiation therapy was continued during that week. Gemcitabine was thereafter resumed weekly for another 3 weeks or until the patient completed the radiation therapy (whichever was earlier). Five patients were treated at each dose level. The dose of the drug was escalated in increments of 50 mg/m2 if the toxicity was acceptable at the previous level until the maximum tolerated dose was established. Thirteen patients with advanced unresectable colorectal cancer and 12 patients with advanced unresectable pancreaticobiliary cancers were enrolled on the study. Radiation was delivered at 180 cGy/fraction to a total dose of 4000 cGy ± boost. Because toxicity was severe at the 150 mg/m2 dose level, three additional patients were entered at this dose level. The dose was then dropped to 125 mg/m2, and five more patients were entered at this dose level. Two additional patients were then added in orderto assess toxicity. Patient follow-up ranged from 4 to 22 months, and the median was 8 months. RESULTSAll patients were evaluable for toxicity. The doses of 50 and 100 mg/m2 were well tolerated, but at 150 mg/m2, six of eight patients experienced grade 3 or greater toxicity. The dose was de-escalated to 125 mg/m2, and three of seven patients showed grade 3 diarrhea and weight loss. Clinical tumor response was evaluable in 20 patients. Ten patients had a complete clinical response (50%), five patients had a partial response (25%), three patients had no response, and two patients had progression of disease. No patients experienced late toxicities related to either gemcitabine administration or radiation therapy. Twelve patients are currently alive. CONCLUSIONBased on these results, it appears that the maximum tolerated dose for weekly 24-hour infusion of gemcitabine combined with radiation therapy is 100 mg/m2. Gemcitabine appears to be a potent radiation sensitizer, and when combined with radiation therapy, it has shown encouraging tumor responses. In this study, we found an overall response rate of 75% in patients with locally advanced stage of disease. Further evaluation of gemcitabine at 100 mg/m2 is being undertaken in preparation for a confirmatory multi","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"14 1","pages":"255–262"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74297148","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}
Pub Date : 2002-05-01DOI: 10.1097/00130404-200205000-00010
T. J. Robnett, M. Machtay, S. Hahn, J. Shrager, J. Friedberg, L. Kaiser
PURPOSEPositive links between hemoglobin level and therapeutic tumor response are well documented in carcinoma of the cervix and the head and neck, but little evidence of such a link exists for lung cancer. We analyzed our series of patients treated with preoperative chemoradiation for stage MIA non-small cell lung carcinoma. PATIENTS AND METHODSBetween June 1992 and February 2000, 41 consecutive patients with clinical stage IIIA (N2, documented by mediastinoscopy or another invasive procedure) non-small cell lung carcinoma received preoperative-intent chemoradiation. The median preoperative radiation dose was 48.6 Gy, and all patients received cisplatin- or paclitaxel-based chemotherapy. Response was graded on a four point scale: (1) progressive disease before surgery and/or technically inoperable; (2) stable disease with resection performed, but specimen containing > 50% viable tumor; (3) partial response with specimen containing < 50% tumor; and (4) complete response or near-complete response: RO resection with no residual carcinoma or pTINO with only microscopic residual foci. Pretreatment hemoglobin values were correlated with pathological outcome using ANOVA and the non-parametric test for trend across ordered groups. RESULTSThe mean hemoglobin level for groups 1 through 4 was 11.8, 12.1, 12.5, and 13.2 respectively, and the association was statistically significant. If the analysis was limited to patients actually undergoing surgery (eliminating group 1), the association remained significant. The nonparametric test for trend across ordered groups was also significant with and without group 1. DISCUSSIONOur analysis supports the hypothesis that response to chemoradiation of non-small cell lung carcinoma improves with increasing hemoglobin levels.
{"title":"Pathological Response to Preoperative Chemoradiation Worsens with Anemia in Non‐‐‐Small Cell Lung Cancer Patients","authors":"T. J. Robnett, M. Machtay, S. Hahn, J. Shrager, J. Friedberg, L. Kaiser","doi":"10.1097/00130404-200205000-00010","DOIUrl":"https://doi.org/10.1097/00130404-200205000-00010","url":null,"abstract":"PURPOSEPositive links between hemoglobin level and therapeutic tumor response are well documented in carcinoma of the cervix and the head and neck, but little evidence of such a link exists for lung cancer. We analyzed our series of patients treated with preoperative chemoradiation for stage MIA non-small cell lung carcinoma. PATIENTS AND METHODSBetween June 1992 and February 2000, 41 consecutive patients with clinical stage IIIA (N2, documented by mediastinoscopy or another invasive procedure) non-small cell lung carcinoma received preoperative-intent chemoradiation. The median preoperative radiation dose was 48.6 Gy, and all patients received cisplatin- or paclitaxel-based chemotherapy. Response was graded on a four point scale: (1) progressive disease before surgery and/or technically inoperable; (2) stable disease with resection performed, but specimen containing > 50% viable tumor; (3) partial response with specimen containing < 50% tumor; and (4) complete response or near-complete response: RO resection with no residual carcinoma or pTINO with only microscopic residual foci. Pretreatment hemoglobin values were correlated with pathological outcome using ANOVA and the non-parametric test for trend across ordered groups. RESULTSThe mean hemoglobin level for groups 1 through 4 was 11.8, 12.1, 12.5, and 13.2 respectively, and the association was statistically significant. If the analysis was limited to patients actually undergoing surgery (eliminating group 1), the association remained significant. The nonparametric test for trend across ordered groups was also significant with and without group 1. DISCUSSIONOur analysis supports the hypothesis that response to chemoradiation of non-small cell lung carcinoma improves with increasing hemoglobin levels.","PeriodicalId":22430,"journal":{"name":"The Cancer Journal","volume":"24 1","pages":"263–267"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84843710","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}
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