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2.
Semin Vasc Surg ; 29(3): 120-125, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27989317

ABSTRACT

Hostile infrarenal aortic neck anatomy presents a challenge for the endovascular treatment of abdominal aortic aneurysm. Open surgical repair has been seen as the gold standard treatment for juxtarenal abdominal aortic aneurysm; however, endovascular techniques are now becoming more prevalent, particularly in patients deemed high risk for morbidity and mortality with open repair. The morphology of an aneurysm is a determinant of long-term outcomes, and short aneurysm necks are associated with poorer outcomes and a higher rate of secondary reinterventions. Parallel grafts have been used in combination with endovascular aneurysm repair to elongate the sealing zone into the paravisceral segment of the aorta. This technique is associated with a risk of proximal Type I endoleak due to "guttering." This risk may be decreased when parallel grafts are used in combination with endovascular aneurysm sealing and, as such, this technique may represent an alternative to current techniques for the treatment of juxtarenal abdominal aortic aneurysm, such as the use of conventional bifurcated grafts (with or without parallel grafts) and fenestrated endovascular stent grafts.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis , Endovascular Procedures/instrumentation , Stents , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortography/methods , Blood Vessel Prosthesis Implantation/adverse effects , Computed Tomography Angiography , Endoleak/etiology , Endoleak/prevention & control , Endovascular Procedures/adverse effects , Humans , Prosthesis Design , Registries , Risk Factors , Treatment Outcome
3.
Ann Oncol ; 27(5): 908-13, 2016 05.
Article in English | MEDLINE | ID: mdl-26884588

ABSTRACT

BACKGROUND: Efforts to reduce the late toxicity associated with chemoradiation (CRT) for locally advanced head and neck squamous cell cancer (LA-HNSCC) have focused on radiotherapy (RT) dose de-escalation. In this phase I/II protocol investigating the addition of everolimus to induction chemotherapy (IC), we incorporated a novel response-adapted volume de-escalation (RAVD) approach using IC response to guide the extent of RT volume reduction. PATIENTS AND METHODS: Patients with measurable LA-HNSCC received two cycles of IC (cisplatin, paclitaxel, cetuximab ± everolimus). Patients with ≥50% reduction in the sum of tumor diameters [good response (GR)] received TFHX (paclitaxel, fluorouracil, hydroxyurea, and 1.5 Gy twice daily RT every other week) to a dose of 75 Gy with the single planning target volume (PTV1) encompassing exclusively gross disease. Patients with <50% response [non-response (NR)] were treated with TFHX encompassing PTV1 and the next nodal station at risk (PTV2) to a dose of 45 Gy followed by a sequential boost to PTV1 to a dose of 75 Gy. RESULTS: Ninety-four patients were enrolled. Randomization to everolimus was discontinued on interim analysis after 50 patients due to futility. IC response was evaluable in 89 patients. Thirty-seven patients (41.6%) had GR and 52 (58.4%) had NR. There was a trend for improved progression-free (P = 0.086) but not overall survival (P = 0.94) for GR versus NR. The 2-year PFS and OS were 86.0% and 83.5% for GR and 68.7% and 85.4% for NR, respectively. NR were significantly more likely to undergo G-tube placement during treatment (50.0% GR versus 73.5% NR, P = 0.040) and be G-tube dependent at 6-month follow-up (5.7% GR versus 32.6% NR, P = 0.005). CONCLUSIONS: The addition of everolimus to IC was not beneficial. The elimination of elective nodal coverage in patients with GR to IC did not appear to compromise outcomes and resulted in significantly decreased late toxicity. Further investigation of RAVD is warranted. CLINICALTRIALSGOV: NCT01133678.


Subject(s)
Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Adult , Aged , Carcinoma, Squamous Cell/pathology , Chemoradiotherapy/adverse effects , Combined Modality Therapy , Everolimus/administration & dosage , Female , Head and Neck Neoplasms/pathology , Humans , Induction Chemotherapy , Male , Middle Aged , Neoplasm Staging , Remission Induction
4.
Ann Oncol ; 26(1): 198-205, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25361984

ABSTRACT

BACKGROUND: Human papillomavirus (HPV) has emerged as a causative agent and positive prognostic factor for oropharyngeal (OP) head and neck squamous cell cancer (HNSCC). This prompts inquiry into whether therapy improvements or increasing incidence of HPV drives the apparent improvements in HNSCC outcomes observed in non-randomized clinical trials. PATIENTS AND METHODS: We reviewed all locoregionally advanced HNSCC patients treated with chemotherapy and radiation in prospective institutional trials at a single institution. Patients were divided into three groups (1, 2, 3) according to treatment time period (1993-1998, 1999-2003, 2004-2010, respectively). We reasoned that if a favorable trend was observed over time in OP but not non-OP patients, HPV status may be confounding treatment effects, whereas this would be unlikely if both subgroups improved over time. RESULTS: Four hundred and twenty-two patients were identified with OP (55.7%) and non-OP (44.3%) HNSCC. Five-year OP overall survival (OS) improved from 42.3% (group 1) to 72.5% (group 2), and 78.4% (group 3), adjusted P = 0.0084. Non-OP 5-year OS was 51.0% (group 1), 58.8% (group 2), and 66.3% (group 3), adjusted P = 0.51. Five-year recurrence-free survival (RFS) improved for OP groups from 42.3% to 68.4% to 75.8% (adjusted P = 0.017). Non-OP 5-year RFS was 42.9%, 53.6%, and 61.7% for sequential groups (adjusted P = 0.30). Five-year OP distant failure-free survival (DFFS) improved from 42.3% to 71.1% to 77.8% (adjusted P = 0.011). Five-year non-OP DFFS was 46.9%, 57.1%, and 66.0% for sequential groups (adjusted P = 0.38). CONCLUSIONS: Over the past two decades, OP HNSCC outcomes improved significantly, while non-OP outcomes only trended toward improvement. Although our patients are not stratified by HPV status, improving OP outcomes are likely at least partly due to the increasing HPV incidence. These data further justify trial stratification by HPV status, investigations of novel approaches for carcinogen-related HNSCC, and current de-intensification for HPV-related HNSCC.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Oropharyngeal Neoplasms , Papillomavirus Infections/epidemiology , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/virology , Female , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/virology , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Oropharyngeal Neoplasms/diagnostic imaging , Oropharyngeal Neoplasms/drug therapy , Oropharyngeal Neoplasms/virology , Papillomaviridae , Prospective Studies , Radiography , Smoking , Squamous Cell Carcinoma of Head and Neck , Treatment Outcome
5.
Ann Oncol ; 24(3): 769-76, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23104721

ABSTRACT

BACKGROUND: AdGV.EGR.TNF.11D (TNFerade™ Biologic) is a replication-deficient adenoviral vector expressing human tumor necrosis factor alpha (TNF-α) under the control of the chemoradiation-inducible EGR-1 promoter. TNF-α has been shown to function as a radiation sensitizer. We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of TNFerade™ Biologic, when added to chemoradiotherapy in poor prognosis patients with recurrent, previously irradiated head and neck cancer (HNC). METHODS: TNFerade™ Biologic was injected intratumorally on day 1 of each 14-day cycle and dose-escalated in log increments from 4 × 10(9) to 4 × 10(11) PU. Daily radiation, infusional 5-fluorouracil (5-FU), and hydroxyurea were given on days 1-5 for seven cycles (FHX). Tumor biopsies were obtained before, during, and after treatment. RESULTS: Fourteen patients were treated. DLT was reached at a dose level of 3 (4 × 10(11) PU) with three thrombotic events. The response rate was 83.3%. The median survival was 9.6 months. One patient (7.1%) remained alive 3 years after treatment. Biopsies were obtained in 90% of patients. Nearly all tumors expressed adenovirus receptors, TNF-α, and TNF-α receptors. Adenoviral DNA was detected in three biopsies from one patient. CONCLUSIONS: TNFerade™ Biologic can be safely integrated with FHX chemoradiotherapy at an MTD of 4 × 10(10) PU. Monitoring for thrombotic events is indicated.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/therapy , DNA/administration & dosage , Head and Neck Neoplasms/therapy , Radiation-Sensitizing Agents/administration & dosage , Adult , Aged , Carcinoma, Squamous Cell/mortality , Chemoradiotherapy , DNA/genetics , Dose Fractionation, Radiation , Female , Fluorouracil/administration & dosage , Genetic Therapy , Head and Neck Neoplasms/mortality , Humans , Hydroxyurea/administration & dosage , Kaplan-Meier Estimate , Male , Maximum Tolerated Dose , Middle Aged , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Intensity-Modulated , Retreatment , Squamous Cell Carcinoma of Head and Neck , Treatment Outcome
6.
Oral Oncol ; 49(3): 277-82, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23102863

ABSTRACT

PURPOSE: Current standard therapy for nasopharyngeal carcinoma (NPC) is concurrent chemoradiation based on randomized data. However, limited randomized data exist to support the addition of induction chemotherapy (ICT). METHODS: 58 Patients with NPC were treated from 1990 to 2010. All patients received platinum-based ICT. All 58 patients were treated with chemoradiation, 57 in a week-on/week-off (WOWO) fashion. Concurrent chemotherapy included hydroxyurea/5-fluorouracil for all patients. Median radiation dose was 70 Gy. No patient received adjuvant chemotherapy. RESULTS: AJCC 2009 stage was II=13, III=21, IVa=13, and IVb=11. Median follow-up for surviving patients was 66 months. Response to ICT was complete response (CR) 17% and partial response (PR) 64%. The CR rate after chemoradiation was 96%. Five-year actuarial freedom from local failure (FFLF), freedom from distant failure (FFDF), cause-specific survival (CSS), and overall survival (OS) was 98%, 90%, 90%, and 76%, respectively. Analysis of pediatric patients (n=9) demonstrated 5-year actuarial FFLF, FFDF, CSS, and OS of 100%, 88%, 80%, and 80%, respectively. CONCLUSIONS: ICT followed by concurrent chemoradiation demonstrates excellent FFLF, FFDF, CSS, and OS with tolerable toxicity. Induction chemotherapy followed by concurrent chemoradiation for patients with NPC should be explored further in a randomized setting.


Subject(s)
Carcinoma/drug therapy , Chemoradiotherapy/methods , Induction Chemotherapy/methods , Nasopharyngeal Neoplasms/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/radiotherapy , Carcinoma/secondary , Chemotherapy, Adjuvant , Child , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Hydroxyurea/administration & dosage , Male , Middle Aged , Nasopharyngeal Neoplasms/radiotherapy , Neoadjuvant Therapy , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Platinum/administration & dosage , Radiotherapy Dosage , Remission Induction , Survival Rate , Treatment Outcome , Young Adult
7.
Ann Oncol ; 22(11): 2501-2507, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21385883

ABSTRACT

BACKGROUND: Concurrent chemoreirradiation therapy (CRRT) offers a therapeutic option for patients with locoregionally recurrent squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that response to induction chemotherapy (IC) would improve outcome and predict increased survival. PATIENTS AND METHODS: Subjects with recurrent SCCHN not amenable to standard therapy were eligible. IC consisted of two 28-day cycles of gemcitabine and pemetrexed on days 1 and 14, followed by surgical resection, if appropriate, and/or CRRT consisting of carboplatin, pemetrexed, and single daily fractionated radiotherapy. RESULTS: Thirty-five subjects were enrolled, 31 were assessable for response, with 11 responders [response rate = 35%; 95% confidence interval (CI) 19.2-54.6]. Among 24 subjects who started CRRT, 11 were assessable for radiographic response, 4 complete response, 2 partial response, and 5 progressive disease. Median progression-free survival and overall survival (OS) were 5.5 months (95% CI 3.6-8.3) and 9.5 months (95% CI 7.2-15.4), respectively. One-year OS was 43% (95% CI 26% to 58%). Subjects who responded to IC had improved survival (P = 0.02). Toxic effects included mucositis, dermatitis, neutropenia, infection, hemorrhage, dehydration, and pain. CONCLUSIONS: The combination of pemetrexed plus gemcitabine was active and well tolerated in recurrent SCCHN. Response to IC may help stratify prognosis and offer an objective and dynamic metric in recurrent SCCHN patients being considered for CRRT.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/radiotherapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Squamous Cell/surgery , Combined Modality Therapy/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Female , Glutamates/administration & dosage , Glutamates/adverse effects , Guanine/administration & dosage , Guanine/adverse effects , Guanine/analogs & derivatives , Head and Neck Neoplasms/surgery , Humans , Induction Chemotherapy , Male , Middle Aged , Pemetrexed , Prospective Studies , Radiotherapy/adverse effects , Squamous Cell Carcinoma of Head and Neck , Gemcitabine
8.
Ann Oncol ; 22(10): 2304-9, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21330337

ABSTRACT

INTRODUCTION: We conducted a randomized phase II study to evaluate the impact of adding bevacizumab (B) to 5-fluorouracil (5-FU), hydroxyurea (HU), and radiotherapy (FHX) for intermediate-stage and select T4 head and neck squamous cell cancers (HNSCC). PATIENTS AND METHODS: Eligible patients had newly diagnosed HNSCC. Randomization was 2:1 in favor of BFHX. All patients received 500 mg HU p.o. b.i.d., 600 mg/m(2)/day continuous infusion 5-FU, and b.i.d. radiotherapy with or without bevacizumab 10 mg/kg administered on day 1 of each 14-day cycle. Patients received five cycles consisting of chemoradiotherapy for 5 days followed by 9 days without therapy. RESULTS: Twenty-six patients were enrolled (19 BFHX and 7 FHX). The study was halted following unexpected locoregional progression. Two-year survival was 68%; 89% treated with FHX and 58% (95% confidence interval 33% to 78%) treated with BFHX. Two-year locoregional control was 80% after chemoradiotherapy and 85% after surgical salvage. All locoregional progression occurred in T4 tumors randomized to BFHX. Two patients receiving BFHX died during therapy, and one died shortly after therapy. No catastrophic bleeding events were seen. CONCLUSIONS: Locoregional progression seen in T4N0-1 tumors treated with BFHX was unexpected and led to study termination. The addition of bevacuzimab to chemoradiotherapy for HNSCC should be limited clinical trials.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Bevacizumab , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Combined Modality Therapy , Disease Progression , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/surgery , Humans , Hydroxyurea/administration & dosage , Male , Middle Aged , Neoplasm Staging , Radiotherapy Dosage , Squamous Cell Carcinoma of Head and Neck
9.
Eur J Vasc Endovasc Surg ; 41(2): 264-6, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21130009

ABSTRACT

INTRODUCTION: Thorascopic sympathectomy is a widely used procedure for the treatment of intractable palmar hyperhidrosis. REPORT: A 24-year-old woman who underwent thorascopic sympathectomy for hyperhidrosis in 2005 presented on more than 30 occasions with recurrent right distal upper limb ischaemia secondary to repetitive episodes of vasospasm. The patient did not have preoperative symptoms consistent with Raynaud's syndrome. We observed a reduction in the symptomatic relief offered by Iloprost treatment over a period of five years. DISCUSSION: This is the first report of distal upper limb ischaemia following thorascopic sympathectomy. We highlight the development of resistance to repeated Iloprost infusions that we observed in this case.


Subject(s)
Hyperhidrosis/surgery , Ischemia/etiology , Spasm/etiology , Sympathectomy/adverse effects , Thoracoscopy/adverse effects , Upper Extremity/blood supply , Vascular Diseases/etiology , Drug Resistance , Female , Humans , Iloprost/administration & dosage , Infusions, Parenteral , Ischemia/diagnostic imaging , Ischemia/drug therapy , Radiography , Recurrence , Spasm/diagnostic imaging , Spasm/drug therapy , Sympathectomy/methods , Treatment Outcome , Vascular Diseases/diagnostic imaging , Vascular Diseases/drug therapy , Vasodilator Agents/administration & dosage , Young Adult
10.
Ann Oncol ; 19(10): 1787-94, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18539617

ABSTRACT

BACKGROUND: We hypothesized induction chemotherapy (IndCT) would improve distant control (DC) without compromising locoregional control (LRC) for locoregionally advanced head and neck cancer patients. Additionally, we systematically lowered radiotherapy (RT) doses attempting to maintain LRC while decreasing toxicity. PATIENTS AND METHODS: Stages III-IV (M0) locoregionally advanced head and neck cancer patients received carboplatin/paclitaxel (Taxol) IndCT followed by four or five cycles consisting of 5 days of paclitaxel, fluorouracil, hydroxyurea, and BID RT followed by a nine day break. RT dose to gross disease (high risk), intermediate, and low-risk volumes were reduced from cohort A (n = 68): 75, 60, and 45 Gy; to cohort B (n = 64): 75, 54, and 39 Gy; then cohort C (n = 90): 72, 51, and 36 Gy. RESULTS: A total of 222 patients accrued from November 1998 to September 2002. Median follow-up is 56 months. In all, 93/96/76% achieved a complete response to concurrent chemoradiotherapy (CRT) in cohort A/B/C. Three- and 5-year overall survivals (OSs) are 68% and 62%, respectively. Five-year LRC and DC are 91% and 87%, respectively. Response to IndCT predicted for OS, LRC, and time to progression (TTP). Cohort C patients had similar OS (P = 0.95), LRC, and DC, but worse (TTP) (P = 0.027). CONCLUSIONS: IndCT before CRT reduces distant progression while maintaining high LRC. The cohort B schedule provides the best therapeutic ratio. A randomized trial investigating IndCT before CRT has been initiated.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Cohort Studies , Combined Modality Therapy , Disease-Free Survival , Dose-Response Relationship, Radiation , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Head and Neck Neoplasms/pathology , Humans , Hydroxyurea/administration & dosage , Hydroxyurea/adverse effects , Male , Middle Aged , Neoplasm Staging , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Remission Induction
11.
Ann Oncol ; 19(9): 1650-4, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18467314

ABSTRACT

BACKGROUND: Randomized trials established chemoradiotherapy as standard treatment for advanced laryngeal cancer. Patients with large-volume T4 disease (LVT4) were excluded from these trials. The purpose of this study was to report T4 laryngeal cancer patient outcome, including those with LVT4 disease, treated with chemoradiotherapy. PATIENTS AND METHODS: This study is a retrospective subset analysis of 32 patients with T4 laryngeal carcinoma including LVT4 tumors treated on three consecutive protocols investigating paclitaxel (Taxol), 5-fluorouracil, hydroxyurea, and 1.5-Gy twice daily (BID) radiotherapy (TFHX). RESULTS: Median follow-up is 43 months. Four-year locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and laryngectomy-free survival (LFS) was 71%, 67%, 53%, and 86%, respectively. Four patients required laryngectomy for recurrent or persistent disease. Of disease-free patients with >or=1 year follow-up, 90% demonstrated normal or understandable speech. None required laryngectomy for complications. Among LVT4 patients, 4-year LRC, DFS, OS, and LFS was 71%, 65%, 56%, and 81%, respectively. Induction chemotherapy improved 4-year LRC (90% versus 46%, P = 0.03) and DFS (84% versus 42%, P = 0.03). CONCLUSIONS: Promising control and functional outcomes are achieved with TFHX for T4 laryngeal patients. LVT4 disease had outcomes similar to patients with less advanced disease treated on Radiation Therapy Oncology Group 91-11. Induction chemotherapy improved outcomes, warranting further investigation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Laryngeal Neoplasms/drug therapy , Laryngeal Neoplasms/radiotherapy , Adult , Aged , Area Under Curve , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Combined Modality Therapy , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Hydroxyurea/administration & dosage , Immunohistochemistry , Kaplan-Meier Estimate , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Organ Preservation/methods , Paclitaxel/administration & dosage , Probability , Quality of Life , Radiotherapy Dosage , Retrospective Studies , Risk Assessment , Survival Analysis , Treatment Outcome
12.
Phys Rev Lett ; 95(5): 052003, 2005 Jul 29.
Article in English | MEDLINE | ID: mdl-16090867

ABSTRACT

A high statistics measurement of the D(s)+ lifetime from the Fermilab fixed-target FOCUS photoproduction experiment is presented. We describe the analysis of the two decay modes, D(s)+ --> phi(1020)pi+ and D(s)+ -->K*(892)0K+, used for the measurement. The measured lifetime is 507.4 +/- 5.5(stat) +/- 5.1(syst) fs using 8961 +/- 105 D(s)+ --> phi(1020)pi+ and 4680 +/- 90 D(s)+ --> K*(892)0K+ decays. This is a significant improvement over the present world average.

13.
Ann Oncol ; 15(8): 1179-86, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15277256

ABSTRACT

BACKGROUND: Locoregionally advanced, stage IV head and neck cancer has traditionally carried a poor prognosis. We sought to assess changes in patterns of failure, prognostic factors for recurrence, and overall outcome, using two different strategies of chemoradiotherapy conducted in prospective, multi-institutional phase II trials. PATIENTS AND METHODS: Three hundred and thirty-seven stage IV patients were treated from 1989 to 1998. We compared locoregional and distant recurrence rates, overall survival and progression-free survival from two different treatment strategies: intensive induction chemotherapy followed by split-course chemoradiotherapy (type 1, n=127), or intensified, split-course, hyperfractionated multiagent chemoradiotherapy alone (type 2, n=210). Univariate and multivariate analyses of 12 chosen covariates were assessed separately for the two study types. RESULTS: The pattern of failure varied greatly between study types 1 and 2 (5-year locoregional failure of 31% and 17% for study types 1 and 2, respectively, P=0.01; 5-year distant failure rate of 13% and 22% for study types 1 and 2, P=0.03). Combined 5-year overall survival was 47% [95% confidence interval (CI) 41% to 53%) and progression-free survival was 60% (95% CI 55% to 66%). Both treatment strategies yielded similar survival rates. Poor overall survival and distant recurrence were best predicted by advanced nodal stage. Locoregional recurrence was extremely rare for patients with T0-T3 tumor stage, regardless of lymph-node stage. CONCLUSIONS: This analysis suggests that pattern of failure in primary head and neck cancer may be dependent upon treatment strategy. Randomized clinical trials of induction chemotherapy are warranted as a means to determine if a decrease in distant metastases can lead to an increase in survival rates in the setting of effective chemoradiotherapy for locoregional control. Additionally, this analysis provides impetus for randomized clinical trials of organ preservation chemoradiotherapy in sites outside the larynx and hypopharynx.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Adult , Aged , Clinical Trials, Phase II as Topic , Combined Modality Therapy , Disease-Free Survival , Dose Fractionation, Radiation , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Head and Neck Neoplasms/pathology , Humans , Hydroxyurea/administration & dosage , Male , Middle Aged , Neoplasm Metastasis , Prognosis , Prospective Studies
14.
Ann Oncol ; 14(8): 1306-11, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12881397

ABSTRACT

BACKGROUND: Our aim was to explore the use of concurrent chemoradiotherapy in the management of patients with squamous cell carcinoma of the head and neck from an occult primary (HNCOP). PATIENTS AND METHODS: From 1991 to 2000, 25 patients with T0N2M0 or T0N3M0 HNCOP were entered into five sequential phase II clinical trials. Chemoradiotherapy consisted of a split course of radiotherapy with concurrent 5-fluorouracil and hydroxyurea either alone or with cisplatin, or paclitaxel. Two of the five protocols incorporated induction chemotherapy. RESULTS: Nodal stage was N2a in five patients (20%), N2b in 13 (52%), N2c in one (4%) and N3 in six (24%). Twenty-two patients (88%) underwent neck dissection; 14 of 22 patients underwent neck dissection before initiating protocol therapy. Total radiation doses of 55-75 Gy (median 60 Gy) were delivered; radiation fields included the potential sites of mucosal primaries and the neck bilaterally. Selected patients received a radiation boost to the involved neck. With a median follow-up of 3.9 years, three patients have progressed (one local, two distant) and seven patients have died. Deaths were due to disease progression (three) or unrelated causes (four). No metachronous primaries developed. The 5-year progression-free and overall survival was 87% and 75%, respectively. CONCLUSION: Combined-modality treatment with intensive chemoradiotherapy results in excellent disease control and long-term survival for patients with N2-N3 HNCOP and compares favorably with traditional therapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Squamous Cell/secondary , Carcinoma, Squamous Cell/therapy , Head and Neck Neoplasms/secondary , Head and Neck Neoplasms/therapy , Neoplasms, Unknown Primary/pathology , Adolescent , Adult , Aged , Carcinoma, Squamous Cell/mortality , Combined Modality Therapy , Disease-Free Survival , Female , Follow-Up Studies , Head and Neck Neoplasms/mortality , Humans , Male , Middle Aged , Neoplasm Staging , Probability , Radiation Dosage , Radiotherapy, Adjuvant , Risk Assessment , Survival Analysis , Treatment Outcome
15.
J Clin Oncol ; 19(7): 1961-9, 2001 Apr 01.
Article in English | MEDLINE | ID: mdl-11283128

ABSTRACT

PURPOSE: To improve local disease control and survival with organ preservation, we conducted a phase II multi-institutional trial with a concomitant taxane-based chemotherapy and hyperfractionated radiation regimen. PATIENTS AND METHODS: Sixty-four patients with locally advanced squamous cancers (stage IV, 98%; N2/3, 81%) were treated on an intensive regimen consisting of 5-day (120-hour) infusions of paclitaxel (20 mg/m(2)/d) and fluorouracil (600 mg/m(2)/d), oral hydroxyurea 500 mg every 12 hours for 11 doses, and radiation 1.5 Gy bid (T-FH2X). Chemoradiation was administered concomitantly on days 1 to 5 of each 14-day cycle. A full treatment course consisted of five cycles during a 10-week period to a total radiation dose of 72 to 75 Gy. RESULTS: The median follow-up for the group is 34 months. At 3 years, progression-free survival is 63%, locoregional control is 86%, and systemic control is 79%; overall survival is 60%. Seventeen patients died of recurrent cancer, two died of second primary cancers, and four died of other causes. Side effects observed include anemia (22% required transfusion), leucopenia (34%, grade 3 to 4), and mucositis (84%, grade 3 to 4). Organ preservation principles were maintained. At 1 year posttreatment, 61% of patients had severe xerostomia and 47% had compromised swallowing. There was little disturbance of speech quality in 97% of patients at the same follow-up point. CONCLUSION: T-FH2X is a highly active and tolerable concomitant chemotherapy and hyperfractionated radiation regimen that induces sustained local tumor control and holds promise for improved survival with organ preservation in high-risk patients. Identification of less toxic therapy and improved distant disease control are needed. T-FH2X should be tested in a randomized trial and compared with a less intensive concomitant regimen that uses once-daily radiation fractionation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/therapy , Head and Neck Neoplasms/therapy , Administration, Oral , Adult , Aged , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/radiotherapy , Combined Modality Therapy/adverse effects , Dose Fractionation, Radiation , Female , Fluorouracil/administration & dosage , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/radiotherapy , Humans , Hydroxyurea/administration & dosage , Illinois/epidemiology , Infusions, Intravenous , Male , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Paclitaxel/administration & dosage , Quality of Life , Survival Analysis
16.
Cancer J ; 7(2): 140-8, 2001.
Article in English | MEDLINE | ID: mdl-11324767

ABSTRACT

PURPOSE: Locoregionally advanced oropharyngeal cancer has been conventionally treated with either surgery and adjuvant radiotherapy or radiotherapy alone, and clinical and functional outcomes have been poor. Chemoradiotherapy has been demonstrated to improve functional outcome and disease control over conventional treatment in recent randomized head and neck trials. Herein, we report overall survival, progression-free survival, and patterns of failure in locoregionally advanced oropharyngeal cancer treated with induction chemotherapy with or without conservative surgery followed by concomitant chemoradiation. MATERIALS AND METHODS: Three cycles of induction chemotherapy consisting of cisplatin, 5-fluorouracil, leucovorin, and interferon alpha-2b (PFL-IFN) were followed by conservative, organ-sparing surgery for residual disease. All patients then proceeded to concomitant chemoradiation consisting of seven or eight cycles of 5-fluorouracil, hydroxyurea, and a total radiotherapy dose of roughly 7,000 cGy. RESULTS: Sixty-one patients with predominantly stage IV disease were treated. Clinical complete response was observed in 65% of patients after induction therapy. The median follow-up was 68.0 months for survivors and 39.0 months for all patients. At 5 years, overall survival is 51%, progression-free survival is 64%, locoregional control is 70%, and distant control is 89%. Locoregional recurrence accounted for 80% of all initial failures. Only five radical surgeries (none were total glossectomy) were performed for initial disease control. Treatment-related toxicity accounted for four deaths. CONCLUSION: PFL-IFN given with 5-fluorouracil, hydroxyurea, and radiotherapy produces a high rate of cures with organ preservation in a disease group that has traditionally fared poorly. Local and distant disease control and survival rates exceed those observed with more standard treatment approaches involving surgery and radiotherapy. Further investigation into chemoradiotherapy as a curative modality for this disease is warranted.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Neoadjuvant Therapy , Oropharyngeal Neoplasms/drug therapy , Oropharyngeal Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/secondary , Carcinoma, Squamous Cell/surgery , Cisplatin/administration & dosage , Disease-Free Survival , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Humans , Hydroxyurea/administration & dosage , Interferon alpha-2 , Interferon-alpha/administration & dosage , Leucovorin/administration & dosage , Male , Middle Aged , Oropharyngeal Neoplasms/mortality , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/surgery , Recombinant Proteins , Survival Analysis , Treatment Outcome
17.
Midwifery ; 17(1): 2-10, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11207100

ABSTRACT

OBJECTIVE: to examine women's attitudes to being questioned by their midwife, during and after pregnancy, about exposure to violence. DESIGN: an explorative study using content analysis of one open-ended question. SETTING: all antenatal clinics in Uppsala, a medium-sized Swedish university town. PARTICIPANTS: all women registered for antenatal care before 32 weeks of pregnancy, during a period of 6 months. MEASUREMENTS: all women were assessed regarding abuse, using the Abuse Assessment Screen (McFarlane 1993) twice during pregnancy and once again more than four weeks after the birth. On the last occasion the women were asked to respond to an open-ended written question worded: 'Please describe how you felt about being questioned by your midwife at the antenatal clinic concerning violence' Those women who reported violence and those who did not were compared regarding their attitude to being asked about violence. FINDINGS: 879 women were presented with the open-ended question. Eighty per cent found the questioning acceptable, 12% neither acceptable nor unacceptable, 5% both acceptable and unacceptable, and only 3% found it unacceptable. There was no difference between those who reported abuse and those who did not, as to whether the questioning was unacceptable. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: the findings suggest that most pregnant women are not averse to being asked, by their midwife, about exposure to violence. As part of the identification of risk factors that is carried out in every pregnancy, the midwife should ask about exposure to violence at the antenatal clinic. To feel confident when raising the subject of abuse, midwives must be taught about the nature of intimate-partner violence, and appropriate referral and intervention strategies.


Subject(s)
Attitude to Health , Battered Women/psychology , Nurse-Patient Relations , Spouse Abuse/psychology , Adult , Female , Humans , Maternal Welfare , Nursing Methodology Research , Pregnancy , Prenatal Care/methods , Quality of Life , Risk Factors , Surveys and Questionnaires/standards , Sweden
18.
J Psychosom Obstet Gynaecol ; 22(4): 189-97, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11840572

ABSTRACT

All women registered for antenatal care within a Swedish municipality during a 6-month period were assessed regarding acts of violence. The Abuse Assessment Screen was used on two occasions during pregnancy, and once between 4 and 20 weeks after delivery. The efficacy of repeated interviews was investigated, and characteristics of abused and non-abused women were compared. The participation rate was 93% (1038 women). Physical abuse by a close acquaintance or relative during or shortly after pregnancy was reported by 1.3%, and by 2.8% when the year preceding pregnancy was included. The lifetime prevalence of emotional, physical or sexual abuse was 19.4%. Repeated questioning increased the detection of abuse. Women abused during pregnancy reported more preceding ill-health and more elective abortions than non-abused women. Intervention against sexual violence has been on the political agenda in Sweden for several decades. Even so, physical abuse is a risk factor comparable in frequency to obstetric complications such as gestational diabetes and pre-eclampsia. Routines need to be established to make questioning about violence an integral part of the standardized screening for risk factors during pregnancy.


Subject(s)
Mass Screening , Pregnancy/statistics & numerical data , Spouse Abuse/statistics & numerical data , Violence/statistics & numerical data , Abortion, Induced/statistics & numerical data , Adolescent , Adult , Child , Child Abuse, Sexual/statistics & numerical data , Cross-Sectional Studies , Female , Humans , Incidence , Pregnancy Complications/epidemiology , Pregnancy Complications/etiology , Pregnancy Outcome , Prenatal Care , Rape/statistics & numerical data , Risk Factors
19.
Arch Otolaryngol Head Neck Surg ; 126(8): 950-6, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10922226

ABSTRACT

OBJECTIVES: To evaluate the necessity, technical feasibility, and complication rate of neck dissection performed on patients with head and neck cancer after 5 cycles of concomitant chemoradiotherapy (CRT) and to justify a selective neck dissection (SND) approach and define the optimal timing of post-CRT neck dissection. DESIGN AND SETTING: Retrospective analysis in an academic university medical center. PATIENTS: Sixty-nine eligible patients with advanced (stage III and IV) head and neck cancer who have undergone 1 of 4 CRT protocols. Patients ranged in age from 36 to 75 years, and surgical procedures were performed over a 4-year period. Follow-up ranged from 6 to 64 months. INTERVENTION: Neck dissection (most commonly unilateral SND) performed within 5 to 17 weeks after CRT completion. MAIN OUTCOME MEASURES: Complication rate and incidence of positive pathology (viable cancer) in pathologic neck dissection specimens. RESULTS: Seven (10%) of 69 patients developed wound healing complications, 4 (6%) of whom required surgical intervention for ultimate closure. There were no wound infections. Other complications occurred in 11 (16%) of 69 patients and included need for tracheotomy, nerve transection and paresis, and permanent hypocalcemia. Twenty-four (35%) of 69 patients revealed microscopic residual disease. Ten (50%) of 20 patients with N3 neck disease had positive pathology, whereas 14 (36%) of 39 patients with N2 disease had viable carcinoma in the dissection specimen (P =.09 by chi(2) analysis). There was no significant relation between radiologic complete response or partial response and residual microscopic cancer. In 1 patient, disease recurred in the neck after dissection. Mean follow-up time was 30.3 months. CONCLUSIONS: (1) Neck dissection for patients with N2 or greater neck disease after CRT is necessary to eradicate residual disease. (2) The complication rate of SND after CRT with hyperfractionated radiotherapy is low. (3) SNDs are technically feasible when performed within the "window" between the acute and chronic CRT injury (4-12 weeks). (4) SNDs, rather than more radical procedures, appear to be therapeutically appropriate in this group of patients because of the low incidence of disease recurrence in the neck.


Subject(s)
Antineoplastic Agents/therapeutic use , Head and Neck Neoplasms , Neck Dissection , Adult , Aged , Combined Modality Therapy , Feasibility Studies , Female , Follow-Up Studies , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/surgery , Humans , Lymph Nodes/surgery , Male , Middle Aged , Neoplasm Staging , Radiation Dosage , Retrospective Studies , Time Factors , Wound Healing
20.
Ann Oncol ; 11(6): 721-8, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10942062

ABSTRACT

BACKGROUND: Concomitant chemoradiotherapy is an effective treatment modality for advanced head and neck cancer, but improved regimens are needed. We sought to define the toxicities, recommended phase II dose, and outcome of a combination chemotherapy regimen with concomitant hyperfractionated radiotherapy in patients with poor prognosis cancers of the head and neck, including those having received prior curative intent radiotherapy. PATIENTS AND METHODS: From 1995 until 1997, 54 patients were treated, 25 of whom had received a prior full course of radiotherapy to the head and neck. Patients were treated with 5-fluorouracil (5-FU) 600 mg/m2/day continuous infusion x 5 days (days 1-5), hydroxyurea, 500 mg p.o. bid x 11 doses (days 1-6) and paclitaxel (60-150 mg/m2) by one-hour infusion on day 2 using a dose escalation strategy. Radiotherapy was given concomitantly on days 2-6, 150 cGy bid. Each of 4-5 cycles was delivered every other week. RESULTS: The MTD of paclitaxel was 100 mg/m2. The regimen was feasible; radiotherapy was delivered at a median of 7300 cGy and 83% of patients received > or = 80% planned dose intensity. Hematological toxicity, with granulocyte colony stimulating factor, was very mild. Dose limiting toxicities were mucositis and dermatitis. Despite poor prognosis, two-year survival was 45%. CONCLUSIONS: The recommended phase II dose of this regimen is 5-FU 600 mg/m2/day x 120 hours (days 1-5), hydroxyurea 500 mg p.o. b.i.d. x 11 doses (days 1-6), paclitaxel 100 mg/m2 over one hour on day 2, and radiotherapy 150 cGy b.i.d. days 2-6. Concomitant chemotherapy and re-irradiation was feasible on this protocol and resulted in long-term survival in patients without other curative intent options.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Granulocyte Colony-Stimulating Factor/therapeutic use , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Combined Modality Therapy , Female , Fluorouracil/administration & dosage , Humans , Hydroxyurea/administration & dosage , Male , Middle Aged , Paclitaxel/administration & dosage , Prognosis , Recombinant Proteins
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