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Biomedical subjects

David G Pfister

Publications and source records attributed to David G Pfister.

At least 19 recordsLinked to original sources
PubMed2006

A comparison of intensity-modulated radiation therapy and concomitant boost radiotherapy in the setting of concurrent chemotherapy for locally advanced oropharyngeal carcinoma.

PURPOSE: The aim of this study was to compare toxicity/efficacy of conventional radiotherapy using delayed accelerated concomitant boost radiotherapy (CBRT) vs. intensity-modulated radiotherapy (IMRT) in the setting of concurrent chemotherapy (CT) for locally advanced oropharyngeal carcinoma. METHODS AND MATERIALS: Between September 1998 and June 2004, a total of 293 consecutive patients were treated at our institution for cancer of the oropharynx. Of these, 112 had Stage III/IV disease and squamous cell histology. In all, 41 were treated with IMRT/CT and 71 were treated with CBRT/CT, both to a median dose of 70 Gy. Most common CT was a planned two cycles given every 3 to 4 weeks of cisplatin, 100 mg/m2 i.v., but an additional cycle was given to IMRT patients when possible. Both groups were well-matched for all prognostic factors. RESULTS: Median follow-up was 46 months (range, 3-93 months) for the CBRT patients and 31 months (range, 20-64 months) for the IMRT group. Three-year actuarial local-progression-free, regional-progression-free, locoregional progression-free, distant-metastases-free, disease-free, and overall survival rates were 85% vs. 95% (p = 0.17), 95% vs. 94% (p = 0.90), 82% vs. 92% (p = 0.18), 85% vs. 86% (p = 0.78), 76% vs. 82% (p = 0.57), and 81% vs. 91% (p = 0.10) for CBRT and IMRT patients, respectively. Three patients died of treatment-related toxicity in the CBRT group vs. none undergoing IMRT. At 2 years, 4% IMRT patients vs. 21% CBRT patients were dependent on percutaneous endoscopic gastrostomy (p = 0.02). Among those who had > or =20 months follow-up, there was a significant difference in Grade > or =2 xerostomia as defined by the criteria of the Radiation Therapy and Oncology Group, 67% vs. 12% (p = 0.02), in the CBRT vs. IMRT arm. CONCLUSION: In the setting of CT for locally advanced oropharyngeal carcinoma, IMRT results in lower toxicity and similar treatment outcomes when compared with CBRT.

Adult↗
PubMed2006

A Phase II study of SU5416 in patients with advanced or recurrent head and neck cancers.

BACKGROUND: SU5416 (semaxanib) is a synthetic small molecule inhibitor of the tyrosine kinase domain of vascular endothelial growth factor receptor 2 (VEGFR2). This Phase II study was conducted to determine the safety and efficacy of SU5416 in patients with recurrent or metastatic head and neck cancers. PATIENTS AND METHODS: This was an open label, single arm, Phase 2 study for patients who had received no more than 2 cytotoxic regimens. Thirty-five patients received intravenous SU5416 (145 mg/m(2)) twice per week by intravenous catheter. Radiologic imaging for response assessment was planned at the conclusion of each 8 week cycle. Serum VEGF levels and power Doppler ultrasound tumor imaging were explored as potential surrogate markers for SU5416 activity. RESULTS: Thirty-two patients had received prior radiotherapy, including 18 patients who received prior concurrent chemoradiotherapy. Twelve patients had received prior chemotherapy in the recurrent disease setting. Thirty-one patients were evaluable for response. There was one partial response and one minor response. The median number of 8-week cycles received was 1 (range 1-4). Median overall survival was 6.25 months. The most common > or = grade 3 toxicity was headache (31%). There was one fatal carotid artery hemorrhage. Fatigue, nausea, and vomiting were common grade 1-2 adverse events. Power Doppler ultrasound demonstrated decreased tumor vascularity in 5 of 7 patients. CONCLUSIONS: Treatment with SU5416 in patients with head and neck cancers is feasible, but objective responses are rare. Studies evaluating more potent anti-angiogenic agents in this disease are of interest.

Adult↗
PubMed2006

A phase I trial of intermittent high-dose gefitinib and fixed-dose docetaxel in patients with advanced solid tumors.

PURPOSE: Based on our mouse xenograft model demonstrating that intermittent high-dose gefitinib sensitizes tumors to subsequent treatment with taxanes, we initiated this phase I trial to explore docetaxel in combination with escalating doses of intermittent gefitinib (Iressa) given prior to docetaxel. METHODS: This was a phase I study where patients with advanced cancer were treated with escalating doses of gefitinib (1,000, 1,500, 2,250, 3,000 mg) on days 1 and 2 followed by docetaxel (75 mg/m2) on day 3 of a 21 day cycle. Gefitinib pharmacokinetic data were obtained on days 1, 2, and 3 of cycles 1 and 2 at each dose level. RESULTS: 18 patients were enrolled in this study with the most frequent tumor types being non-small cell lung cancer and head and neck squamous cell cancer. The dose-limiting toxicity was neutropenia (n=1 at dose level 2, n=2 at dose level 4). Rash, diarrhea, and fatigue were the most common grade 1-2 toxicities. Pharmacokinetic data indicated no accumulation of gefitinib between cycles 1 and 2 and no clear correlation between gefitinib plasma levels and toxicity. Partial responses were observed in one patient with head and neck squamous cell carcinoma and one patient with anaplastic thyroid cancer. CONCLUSION: The recommended dose for phase II studies is gefitinib 2,250 mg on days 1 and 2, followed by docetaxel 75 mg/m2 on day 3.

Adult↗
PubMed2006

American Society of Clinical Oncology clinical practice guideline for the use of larynx-preservation strategies in the treatment of laryngeal cancer.

PURPOSE: To develop a clinical practice guideline for treatment of laryngeal cancer with the intent of preserving the larynx (either the organ itself or its function). This guideline is intended for use by oncologists in the care of patients outside of clinical trials. METHODS: A multidisciplinary Expert Panel determined the clinical management questions to be addressed and reviewed the literature available through November 2005, with emphasis given to randomized controlled trials of site-specific disease. Survival, rate of larynx preservation, and toxicities were the principal outcomes assessed. The guideline underwent internal review and approval by the Panel, as well as external review by additional experts, members of the American Society of Clinical Oncology (ASCO) Health Services Committee, and the ASCO Board of Directors. RESULTS: Evidence supports the use of larynx-preservation approaches for appropriately selected patients without a compromise in survival; however, no larynx-preservation approach offers a survival advantage compared with total laryngectomy and adjuvant therapy with rehabilitation as indicated. RECOMMENDATIONS: All patients with T1 or T2 laryngeal cancer, with rare exception, should be treated initially with intent to preserve the larynx. For most patients with T3 or T4 disease without tumor invasion through cartilage into soft tissues, a larynx-preservation approach is an appropriate, standard treatment option, and concurrent chemoradiotherapy therapy is the most widely applicable approach. To ensure an optimum outcome, special expertise and a multidisciplinary team are necessary, and the team should fully discuss with the patient the advantages and disadvantages of larynx-preservation options compared with treatments that include total laryngectomy.

Clinical Trials, Phase III as Topic↗
PubMed2006

Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced, squamous cell head and neck cancer: a pilot phase II study of a new combined-modality paradigm.

PURPOSE: Cetuximab is a chimeric monoclonal antibody that targets the epidermal growth factor receptor. Cetuximab has activity in squamous cell carcinoma and enhances both chemotherapy and radiotherapy. We conducted a pilot phase II study of a new combined-modality paradigm of targeted therapy (cetuximab) with chemoradiotherapy. PATIENTS AND METHODS: Eligible patients had stage III or IV, M0, squamous cell head and neck cancer. Treatment included concomitant boost radiotherapy (1.8 Gy/d weeks 1 to 6; boost: 1.6 Gy 4 to 6 hours later weeks 5 to 6; 70 Gy total to gross disease), cisplatin (100 mg/m2 intravenously weeks 1 and 4), and cetuximab (400 mg/m2 intravenously week 1, followed by 250 mg/m2 weeks 2 to 10). RESULTS: Twenty-two patients were enrolled (median age, 57 years; range, 41 to 72 years; median Karnofsky status, 90%; range, 70% to 90%; oropharynx primary tumor, 59% of patients; T4, 36%; N2/3, 77%; stage IV disease, 86%). One patient did not receive study treatment because of an ineligible diagnosis. The severity of expected, acute toxicities was typical of concurrent cisplatin and radiotherapy alone. Grade 3 or 4 cetuximab-related toxicities included acne-like rash (10%) and hypersensitivity (5%). However, the study was closed for significant adverse events, including two deaths (one pneumonia and one unknown cause), one myocardial infarction, one bacteremia, and one atrial fibrillation. With a median follow-up of 52 months, the 3-year overall survival rate is 76%, the 3-year progression-free survival rate is 56%, and the 3-year locoregional control rate is 71%. CONCLUSION: This regimen is not currently recommended outside of the clinical trial setting. Further investigation of its safety profile is needed. However, preliminary efficacy is encouraging, and further development of this targeted combined-modality paradigm is warranted.

Adult↗
PubMed2006

Sensorineural hearing loss in combined modality treatment of nasopharyngeal carcinoma.

BACKGROUND: Combined modality therapy has become the standard of care for nasopharyngeal carcinoma, yet the combined ototoxic effects of radiation and cisplatin are poorly understood. The incidence and severity of sensorineural hearing loss (SNHL) with combined modality therapy was evaluated and the dose-response relation between radiation and hearing loss was investigated. METHODS: Patients with newly diagnosed AJCC Stage II-IVB nasopharynx carcinoma treated from 1994-2003 were identified. The records of 44 ears in 22 patients who received a preirradiation pure tone audiogram and followup audiograms 12+ months postirradiation were included in the analysis. All patients were treated with conformal radiotherapy to 70 Gy and received platinum-based chemotherapy similar to the Intergroup 0099 trial. Composite cochlear dose distributions were calculated. Ototoxicity was measured using intrasubject audiogram comparisons and SNHL was defined as per the American Speech and Hearing Association guidelines, with standard range of speech between 2000-4000 Hz. SNHL was analyzed using Fisher exact test and linear and logistic regression models. RESULTS PATIENT CHARACTERISTICS: median age, 45; 27% Asian; 68% male; 64% WHO III. Median audiologic followup was 29 months (range, 12-76 mos). Mean cochlear dose (Dmean) ranged from 28.4-70.0 Gy (median, 48.5 Gy). SNHL was detected in 25 of the 44 ears (57%) studied. There was an increased risk of SNHL for ears receiving Dmean > 48 Gy compared with those receiving < or = 48 Gy at all frequencies within the range of speech (P = 0.04). Using univariate logistic regression analysis, Dmean to the cochlea, cycles of cisplatin, and time postradiotherapy were independently significant factors in determining the incidence of SNHL (P = 0.02, P = 0.03, and P = 0.04, respectively). In univariate and multivariate linear regression analysis, Dmean was statistically significant at all frequencies in affecting degree of SNHL, whereas the significance of cisplatin and time was variable. CONCLUSIONS: There was a significant increase in risk of SNHL among patients receiving > 48 Gy, suggesting a threshold in cochlear radiation dose-response in the setting of combined modality therapy. This dose should serve as a Dmean constraint maximum for intensity-modulated radiotherapy treatment of nasopharynx carcinoma.

Adolescent↗
PubMed2005

Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline.

PURPOSE: To update the 2000 American Society of Clinical Oncology guideline on colorectal cancer surveillance. RECOMMENDATIONS: Based on results from three independently reported meta-analyses of randomized controlled trials that compared low-intensity and high-intensity programs of colorectal cancer surveillance, and on recent analyses of data from major clinical trials in colon and rectal cancer, the Panel recommends annual computed tomography (CT) of the chest and abdomen for 3 years after primary therapy for patients who are at higher risk of recurrence and who could be candidates for curative-intent surgery; pelvic CT scan for rectal cancer surveillance, especially for patients with several poor prognostic factors, including those who have not been treated with radiation; colonoscopy at 3 years after operative treatment, and, if results are normal, every 5 years thereafter; flexible proctosigmoidoscopy [corrected] every 6 months for 5 years for rectal cancer patients who have not been treated with pelvic radiation; history and physical examination every 3 to 6 months for the first 3 years, every 6 months during years 4 and 5, and subsequently at the discretion of the physician; and carcinoembryonic antigen every 3 months postoperatively for at least 3 years after diagnosis, if the patient is a candidate for surgery or systemic therapy. Chest x-rays, CBCs, and liver function tests are not recommended, and molecular or cellular markers should not influence the surveillance strategy based on available evidence.

Biomarkers, Tumor↗
PubMed2005

Adjuvant chemo- and radiotherapy for poor prognosis head and neck squamous cell carcinomas.

The treatment of squamous cell carcinomas of the head and neck is multidisciplinary, especially when the disease is diagnosed at an intermediate or advanced stage. Very often the clinician chooses between surgery, chemo- and radiotherapy options on the basis of the most recent data from the literature, prior experience in head and neck oncology and patient preferences. Nevertheless, for operable tumors, primary surgery, combined in poor-risk patients with radiation, is traditionally considered as the approach offering the best opportunity of cure. Randomized controlled trials and meta-analyses conducted in the 1990s have demonstrated major improvements not only in loco-regional tumor control, but also in terms of survival when chemotherapy is added to radiotherapy in the post-operative setting. The therapeutic index yielded by the co-administration of cytotoxic agents and ionizing radiation following primary surgery as compared with radiotherapy alone has nevertheless been at the center of many debates recently. Notwithstanding the fact that two randomized trials have recently provided new evidence that adjuvant chemo-radiation in poor-risk patients improves loco-regional control and disease-free survival, a number of questions regarding the optimization of the post-operative approaches remain unanswered. There is remaining need for further research efforts that would enable scientists and clinicians to improve, in the next decade, the management of this complex entity of diseases.

Carcinoma, Squamous Cell↗
PubMed2005

Intensity-modulated radiation therapy (IMRT) for nasopharynx cancer: update of the Memorial Sloan-Kettering experience.

PURPOSE: We previously demonstrated that intensity-modulated radiation therapy (IMRT) significantly improves radiation dose distribution over three-dimensional planning for nasopharynx cancer and reported positive early clinical results. We now evaluate whether IMRT has resulted in improved outcomes for a larger cohort of patients with longer follow-up. METHODS AND MATERIALS: Since 1998, all 74 patients with newly diagnosed, nonmetastatic nasopharynx cancer were treated with IMRT using accelerated fractionation to 70 Gy; 59 received a hyperfractionated concomitant boost, and more recently 15 received once-daily treatment with dose painting. With the exception of Stage I disease (n = 5) and patient preference (n = 1), 69 patients received concurrent and adjuvant platinum-based chemotherapy similar to that in the Intergroup 0099 trial. RESULTS PATIENT CHARACTERISTICS: median age 45; 32% Asian; 72% male; 65% World Health Organization III; 6% Stage I, 16% Stage II, 30% Stage III, 47% Stage IV. Median follow-up is 35 months. The 3-year actuarial rate of local control is 91%, and regional control is 93%; freedom from distant metastases, progression-free survival, and overall survival at 3 years are 78%, 67%, and 83%, respectively. There was 100% local control for Stage T1/T2 disease, compared to 83% for T3/T4 disease (p = 0.01). Six patients failed at the primary site, with median time to local tumor progression 16 months; 5 were exclusively within the 70 Gy volume, and 1 was both within and outside the target volume. There is a trend for improved local control with IMRT when compared to local control of 79% for 35 patients treated before 1998 with three-dimensional planning and chemotherapy (p = 0.11). Six months posttherapy, 21%, 13%, 15%, and 0% of patients with follow-up audiograms (n = 24 patients) had Grade 1, 2, 3, and 4 sensorineural hearing loss, respectively. For patients with >1 year follow-up (n = 59), rates of long-term xerostomia were as follows: 26% none, 42% Grade 1, 32% Grade 2, and zero Grade 3. CONCLUSIONS: The pattern of primary site failure within the target volume suggests locally advanced T stage disease may require a higher biologic dose to gross tumor. Rates of severe (Grade 3-4) ototoxicity and xerostomia are low with IMRT as a result of normal-tissue protection. Distant metastases are now the dominant form of failure, emphasizing the need for improved systemic therapy.

Adolescent↗
PubMed2005

Postoperative complications of salvage total laryngectomy.

BACKGROUND: The objectives of the current study were to report the incidence of postoperative complications for salvage total laryngectomy (STL) compared with primary total laryngectomy (PTL) and to identify patient and tumor-related factors predictive of postoperative complications. METHODS: A sample of 183 patients who had received a total laryngectomy were identified from an existing database of 662 patients treated for squamous cell carcinoma of the larynx. PTL and STL were performed in 113 and 70 patients, respectively. Initial therapy in the patients who required salvage surgery included radiotherapy (RT) in 32 (46%) and chemoradiotherapy (CTRT) in 38 (54%). Postoperative complications were recorded for each group and categorized into local, swallowing, airway, and systemic complications. Postoperative complication rates for STL after RT and CTRT were compared with those after PTL by univariate analysis. Patient and tumor-related predictors of complications were identified by univariate and multivariate analyses. RESULTS: The overall mortality rate was 0.5%. Forty percent of all patients developed a postoperative complication after total laryngectomy. Local complications, which were the most frequent, occurred in 52 (28%) patients. Pharyngocutaneous fistula occurred in 31 (17%) patients. Statistical analysis showed that there was a greater number of patients with local wound (45% vs. 25%, P = 0.02) and fistula complications (32% vs. 12%, P = 0.012) in the STL-CTRT group compared with the primary laryngectomy group. Multivariate analysis showed that primary CTRT was an independent predictor of local complications and pharyngocutaneous fistula. CONCLUSIONS: Salvage laryngectomy was more frequently associated with postoperative complications after CTRT compared with PTL. Problems related to local wound healing, especially the development of pharyngocutaneous fistula, constituted the most common postoperative complication in these patients. Multivariate analysis showed that primary CTRT was an independent predictor of local wound complications and pharyngocutaneous fistula.

Adult↗
PubMed2004

Using patients as their own controls for cost evaluation of phase I clinical trials.

PURPOSE: Little is known about the cost of phase I trials in cancer patients compared with that of standard treatments, yet the former is often assumed to be greater than the latter. Our objective was to utilize a new approach, using patients as their own controls, to compare in a pilot study the costs of care for patients on phase I trials with those incurred for standard treatment. PATIENTS AND METHODS: We retrospectively assessed the direct medical costs (DMCs) of 59 patients participating in one of two phase I trials (TRIAL) in solid tumors conducted at Memorial Hospital (MH): (1). perillyl alcohol, and (2). flavopiridol with paclitaxel. Paired-control DMCs were those accrued by the same patient while receiving standard chemotherapy regimens just before (PRE; n = 41) or after (POST; n = 29) the trial at MH, averaged per day. RESULTS: For the 41 PRE patients, the median and mean DMCs per day for the clinical trial versus standard treatment were (US dollars) US dollars 123 v US dollars 133 and US dollars 219 v US dollars 267, respectively. For the 29 POST patients, the median and mean DMCs for the clinical trial versus standard treatment were US dollars 157 v US dollars 152 and US dollars 226 v US dollars 226, respectively. Using a linear mixed model, there was no significant difference between TRIAL and standard treatment DMCs (P =.54). CONCLUSION: Using patients as their own controls represents a new, efficient method for evaluating the cost of phase I trials, and it warrants further study. The results of our pilot study do not suggest that phase I trials always cost payers more than standard treatment.

Adult↗
PubMed2003

Perspectives on the value of American Society of Clinical Oncology clinical guidelines as reported by oncologists and health maintenance organizations.

PURPOSE: Although the American Society of Clinical Onoclogy's (ASCO) Health Services Research (HSR) committee activities have primarily focused on clinical guideline development, little is known about the value placed on these guidelines by the desired end users. ASCO members and Health Maintenance Organizations (HMOs) were surveyed on the value and implementation of ASCO guidelines. In this article, we summarize our findings. METHODS: ASCO members (n = 1500) were queried about whether they had read ASCO's first four clinical guidelines and technology assessment; whether they agreed with the recommendations; whether they used guidelines in clinical practice; and how guidelines had affected reimbursement. HMOs (n = 131) were queried on how they identify, implement, and value the first four ASCO clinical guidelines. RESULTS: The membership survey indicated that ASCO guidelines were read more often by physicians in private healthcare settings compared with physicians in academic practices (P <.02). Disagreement rates were low for all guidelines (range, 1% to 7%). One quarter of respondents reported that the guidelines were difficult to find and difficult to apply to the practice setting, and approximately one tenth of respondents indicated that the guidelines were difficult to evaluate, interpret, or read. The HMO survey indicated that one third of HMOs reported use of ASCO guidelines, with higher rates of usage by larger HMOs and by those with higher National Committee on Quality Assurance (NCQA) ratings. Respondent HMOs valued guidelines for various purposes and used multiple methods of guideline identification and implementation. CONCLUSION: ASCO guidelines are generally highly supported by physicians and HMOs. Additional studies are needed to identify implementation barriers and to see whether guidelines have resulted in improvements in healthcare.

Attitude of Health Personnel↗
PubMed2003

Clinical nodal stage is an independently significant predictor of distant failure in patients with squamous cell carcinoma of the larynx.

OBJECTIVE: To determine the impact of clinical nodal stage on distant metastasis (DM) in patients with squamous cell carcinoma of the larynx (SCCL). METHODS: Six hundred sixty-two previously untreated SCCL patients treated at a tertiary care cancer center from January 1984 to December 1998 were eligible for analysis. The end point of interest was development of DM following treatment. Distant metastasis-free survival (DMFS) was calculated by the Kaplan-Meier method; predictors of outcome were identified by univariate and multivariate analysis. The primary tumor site was glottic in 55%, supraglottic in 40%, and trans/sub glottic in 5%; 40% had locoregionally advanced (stage III/IV) tumors. At initial presentation, 25% of patients (12% N1, 11% N2, and 2% N3) had clinically metastatic nodes. RESULTS: DM were recorded in 67 patients (10%; lung, 45%; soft tissue, 13%; bone, 10%; multiple sites, 28%). The median time to DM was 18 months (range, 1-109). With a median follow-up of 60 months, the 5-year DMFS was 88%. Even after accounting for the type of index treatment, the only significant predictor of worse DMFS on multivariate analysis was a higher clinical N stage (P < 0.0001). The relative risk for DM was 0.5 (95% CI, 0.2-1.4; P = NS) for cN1, 3.2 (95% CI, 1.7-5.9; P < 0.0001) for cN2, and 7.5 (95% CI, 3.1-17.9; P < 0.0001) for cN3 disease compared with clinically N0 patients. CONCLUSION: Regardless of the index treatment modality, primary tumor site, or T stage, a higher clinical N stage at the time of presentation independently and significantly increases the risk of DM in patients with SCCL.

Carcinoma, Squamous Cell↗