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Biomedical subjects

D G Pfister

Publications and source records attributed to D G Pfister.

At least 19 recordsLinked to original sources
PubMed1999

Factors associated with complications in microvascular reconstruction of head and neck defects.

The use of microvascular free tissue transfer has allowed the reconstruction of increasingly complex defects in higher risk patients after head and neck cancer resections. However, the combination of these factors also gives rise to a higher risk for the development of complications. This study was performed to establish the pretreatment factors associated with complication development after microvascular free tissue transfer for the reconstruction of defects resulting from head and neck cancer ablations, with particular attention to the role of comorbid conditions. A retrospective cohort study was conducted including 200 consecutive microvascular free tissue transfers performed for the reconstruction of surgical defects in the head and neck region at a single tertiary care institution. Comorbidity severity was assessed using the Charlson comorbidity index, a novel approach to comorbid staging in this setting. The flap survival rate was 98 percent. Complications developed in 56 cases (28 percent), with multiple complications occurring in 21 of these cases (10.5 percent). Univariate analysis revealed that prior radiation treatment (p = 0.03), anesthesia time over 10 hours (0.05), and advanced Charlson comorbidity grade (0.002) were associated with an increased risk for the development of complications. However, only the presence of advanced Charlson grade proved significant after multivariate analysis (odds ratio 3.9; 95 percent CI = 1.5 to 10.1). In addition, increasing Charlson grade (p = 0.003) and age over 70 years (p = 0.04) correlated with increasing complication severity. Systemic complications occurred in 28 patients (14 percent), with advanced Charlson grade being the only significant factor associated with the development of complications after controlling for confounding factors (odds ratio 3.8; 95 percent CI = 1.5 to 9.7). In patients over 70 years of age, increasing operative time also impacted on the development of systemic complications (p = 0.002), especially in patients with advanced Charlson grades (0.01). Recipient site complications occurred in 30 patients (15 percent), with history of prior radiation therapy being the only factor associated with increased risk by multivariate analysis (odds ratio 2.5; 95 percent CI = 1.1 to 5.7). No factors predicted the development of donor-site complications, which occurred in 11 cases (5.5 percent). The median hospital stay for the entire population was 16 days. The development of complications increased the median hospital stay by 7.5 days (p < 0.001). The effect of the development of complication on hospital stay remained significant even after controlling for the effects of confounding variables (relative risk = 9.87; 95 percent CI = 5.9 to 19.9). Microvascular surgery is a highly successful and relatively safe method for the reconstruction of large head and neck defects. The Charlson comorbidity index grading may be useful for identifying patients at increased risk for the development of complications after microvascular reconstruction, allowing for improved perioperative planning. In addition, patients with prior radiation exposure have a significantly higher risk for developing complications at the recipient site. Although advanced age is not associated with an increased risk for complications, older patients may be more sensitive to the effects of prolonged anesthesia and are likely to develop more severe complications.

Animals↗
PubMed1998

A prospective phase II trial of concomitant chemotherapy and radiotherapy with delayed accelerated fractionation in unresectable tumors of the head and neck.

BACKGROUND: Our study is a prospective evaluation of unresectable malignant cancers of the head and neck treated with concomitant chemotherapy and radiotherapy (RT) using delayed accelerated fractionation (concomitant boost). METHODS: Between January 1988 and March 1995, 82 patients with unresectable cancers of the head and neck were enrolled in this phase II study. Of these, 52 patients were treated and followed for a minimum of 3 years and are the subject of this analysis. All patients had T4 lesions and were stage IV according to the American Joint Committee on Staging Criteria (AJCC). Patients received RT with accelerated fractionation to a total of 70 Gy in 6 weeks using a concomitant-boost technique. Concomitant cis platin (100 mg/M2) was given on days 1 and 22 of RT. Twenty-seven patients received mitomycin-C (7.5 mg/M2) on days 1 and 22, and 1 patient received mitomycin-C on day 1. In addition, 27 patients received adjuvant chemotherapy with cis platin and vinblastine. The mean follow-up was 45 months (range, 36-72 months). The minimum follow-up for surviving patients in 3 years. RESULTS: At 3 years, the local control rate was 58%. Three-year local control rates for paranasal sinus, nasopharynx, oropharynx, and larynx/hypopharynx were 78%, 78%, 64%, and 100%, respectively. For all patients, the distant-metastasis-free survival was 56%, and the overall survival rate was 36%. Patients with oral cavity cancers experienced worse overall survival versus other sites, 0% versus 47% (p = .03). Salivary cancers also showed worse survival versus other sites, 0% versus 47%, but was not statistically significant. Severe acute complications occurred in 34% of patients. Treatment-related toxicity also resulted in the death of 2 patients. Severe late complications occurred in 7% of patients. CONCLUSIONS: Treatment of this poor prognostic group of patients with aggressive chemotherapy and RT produced surprisingly good local control and survival.

Adolescent↗
PubMed1998

Long term results of primary radiotherapy with/without neck dissection for squamous cell cancer of the base of tongue.

BACKGROUND: There are several management options for patients with squamous cell cancer of the base of tongue. We have had an interest in using primary radiotherapy with or without neck dissection, in an effort to provide optimal oncologic as well as functional outcomes. METHODS: From 1981 to 1995, 68 patients with primary squamous cell cancer of the base of tongue were managed with primary radiotherapy, with neck dissection added for those who were initially seen with palpable lymph node metastases. Ages ranged from 35 to 77 years (median age, 55 years). There were 59 men and 9 women. T Stage distribution was: T1, 17; T2, 32; T3, 17; T4, 2. Fifty-eight patients (85%) were initially seen with nodal metastases. Initial treatment generally involved external-beam radiotherapy (EBRT) to the primary site and upper neck (54 Gy) and to the low neck (50 Gy). A 192-Ir brachytherapy boost (20-30 Gy) to the base of tongue was done about 3 weeks later, at the same anesthesia used for the neck dissection. All patients had temporary tracheostomy. Follow-up ranged from 1 month to 151 months (median, 36 months). Nine patients received neoadjuvant chemotherapy as part of a larynx-preservation protocol. RESULTS: Actuarial 5- and 10-year local control is 89% and 89%, distant metastasis free survival is 91% and 76%, disease-free survival is 80% and 67%, and overall survival is 86% and 52%, respectively. Complications occurred in 16%. CONCLUSIONS: Our long term data clearly demonstrate that primary radiotherapy produces excellent oncologic outcomes.

Adult↗
PubMed1997

Long-term regional control after radiation therapy and neck dissection for base of tongue carcinoma.

PURPOSE: Minimal literature exists with 10-year data on neck control in advanced head and neck cancer. The purpose of this study is to determine long-term regional control for base of tongue carcinoma patients treated with primary radiation therapy plus neck dissection. METHODS AND MATERIALS: Between 1981-1996, primary radiation therapy was used to treat 68 patients with squamous cell carcinoma of the base of tongue. Neck dissection was added for those who presented with palpable lymph node metastases. The T-stage distribution was T1, 17; T2, 32; T3, 17; and T4, 2. The N-stage distribution was N0, 10; N1, 24; N2a, 6; N2b, 11, N2c, 8; N3, 7; and Nx, 2. Ages ranged from 35 to 77 (median 55 years) among the 59 males and nine females. Therapy generally consisted of initial external beam irradiation to the primary site (54 Gy) and neck (50 Gy). Clinically positive necks were boosted to 60 Gy with external beam irradiation. Three weeks later, the base of tongue was boosted with an Ir-192 interstitial implant (20-30 Gy). A neck dissection was done at the same anesthesia for those who presented with clinically positive necks, even if a complete clinical neck response was achieved with external beam irradiation. Neoadjuvant cisplatin-based chemotherapy was administered to nine patients who would have required a total laryngectomy if their primary tumors had been surgically managed. The median follow-up was 36 months with a range from 1 to 151 months. Eleven patients were followed for over 8 years. No patients were lost to follow-up. RESULTS: Actuarial 5- and 10-year neck control was 96% overall, 86% after radiation alone, and 100% after radiation plus neck dissection. Pathologically negative neck specimens were observed in 70% of necks dissected after external beam irradiation. The remaining 30% of dissected necks were pathologically positive. These specimens contained multiple positive nodes in 83% despite a 56% overall complete clinical neck response rate to irradiation. Regional failure occurred in only two patients, neither of whom underwent adjuvant neck dissection. Symptomatic neck fibrosis (RTOG grade 3) was not observed. Actuarial 5- and 10-year local control was 88% and 88%, disease-free survival was 80% and 67%, and overall survival was 86% and 52%. CONCLUSION: For base of tongue cancer, most patients can obtain long-term regional control with no severe complications after definitive radiation therapy, plus neck dissection for those who present with lymphadenopathy. Complete clinical regression of palpable neck metastases after irradiation poorly correlates with pathologic outcome. Our current policy is to include neck dissection at the time of implantation for patients who present with palpable neck metastases. We realize that this therapeutic approach may overtreat some patients, but we are reluctant to change our policy in light of these excellent outcomes.

Adult↗
PubMed1997

Detailed quality of life assessment in patients treated with primary radiotherapy for squamous cell cancer of the base of the tongue.

BACKGROUND: This study was conducted to evaluate quality of life in patients treated with primary radiotherapy (RT) for cancer of the base of tongue. METHODS: From 1981 to 1990, 36 patients with primary squamous cell cancer of the base of tongue were managed with primary radiotherapy. Ages ranged from 35 to 71 years (median, 58 years), T Stage was: T1, n = 11; T2, n = 14; T3, n = 10; T4, n = 1. Thirty-one patients (86%) had palpable cervical lymph node metastases at initial examination (N1, n = 16; N2, n = 11; N3, n = 4). Patients received external beam RT to their primary site and necks, followed by a brachytherapy boost to the tongue. Those with neck nodes also had a neck dissection. The median follow-up is 5 years (minimum, 3 years). Actuarial 5-year local control was 85%; regional control was 96%; distant metastases-free survival was 87.5%; and overall survival, 85%. Twenty-nine of the 30 long-term survivors completed (1) Memorial Symptom Assessment Scale (MSAS), (2) Functional Assessment of Cancer Therapy (FACT), (3) Performance Status Scale for Head and Neck Cancer (PSS), and (4) a sociodemographic and economic questionnaire. At the time of cancer diagnosis, 62% were employed full-time, and 21% were employed part-time; 83% were earning > $20,000/year, and 59% were earning > $60,000/year. RESULTS: At follow-up, annual incomes were similar to those at initial examination. Of those who had been working full-time, 72% were still in full-time work, and of those who had been working part-time, 83% were still in part-time work. Average PSS scores were 90 for eating in public, 96 for understandability of speech, and 68 for normalcy of diet. On the MSAS, the following symptoms had prevalence: > 30% xerostomia, difficulty swallowing, decreased energy, pain, worrying, insomnia, cough, drowsy, change in taste, and irritability. Scores on the FACT exceeded published values collected for a mixed cancer population. CONCLUSIONS: The overwhelming majority of patients achieved excellent functional status and quality of life and could maintain their prediagnosis earning potential and employment status after primary radiation for advanced base of tongue cancer.

Actuarial Analysis↗
PubMed1997

Economic considerations in the care of patients with head and neck malignancies.

In an era of cost-consciousness and managed care, quality concerns practice variability attributed to nonmedical factors, and growing attention to outcomes research, there is increasing interest in the economics of malignant disease. This review explores economic issues pertinent to the management of patients with head and neck malignancies. Using economic principles to evaluate medical practice does not uniformly mean that less money should be spent; rather, the intention is to optimize efficiency in the use of limited resources. Accordingly costs are best evaluated in the context of other outcomes of interest. The available economic literature for head and neck tumors is limited; it is often compromised by the use of facility charges as a proxy for true costs and the adoption of a truncated economic perspective. Given the potential health policy implications of such studies, their methodologies and results warrant careful scrutiny. Many opportunities exist for further research.

Cost Control↗
PubMed1997

Initial clinical trial of a selective retinoid X receptor ligand, LGD1069.

PURPOSE: The retinoid response is mediated by nuclear receptors, including retinoic acid receptors (RARs) and retinoid "X" receptors (RXRs). All-trans retinoic acid (RA) binds only RARs, while 9-cis RA is an agonist for both RARs and RXRs. Recently, LGD1069 was identified as a highly selective RXR agonist with low affinity for RARs. We undertook a dose-ranging study to examine the safety, clinical tolerance, and pharmacokinetics of LGD1069 in patients with advanced cancer. PATIENTS AND METHODS: Fifty-two patients received. LGD1069 administered orally once daily at doses that ranged from 5 to 500 mg/m2 for 1 to 41 weeks. Treatment proceeded from a starting dose of 5 mg/m2. Pharmacokinetic sampling was performed on selected patients on days 1, 15, and 29. RESULTS: Reversible, asymptomatic increases in liver biochemical tests were the most common dose-limiting adverse effect. Less prominent reactions included leukopenia, hypertriglyceridemia, and hypercalcemia. Characteristic retinoid toxicities, such as cheilitis, headache, and myalgias/arthralgias, were mild or absent. Two patients with cutaneous T-cell lymphoma experienced major antitumor responses. Pharmacokinetic studies obtained in 27 patients at eight dose levels showed that the day 1 area under the plasma concentration-times-time curves (AUCs) were proportional to dose. At all doses studied, the day 1 AUCs were similar to those on days 15 and 29, indicating a lack of induced metabolism. CONCLUSION: LGD1069 is a unique compound that exploits a newly identified pathway of retinoid receptor biology that may be relevant to tumor-cell proliferation and apoptosis. Further investigation of this drug is warranted. Based on the results of this study, a dose of 300 mg/m2 is recommended for single-agent trials.

Adult↗
PubMed1997

The role of chemotherapy in the curative treatment of head and neck cancer.

Historically, the application of chemotherapy in patients with squamous cell head and neck cancer had been limited to the palliative setting; however, the role of chemotherapy in the definitive management of these tumors has undergone great evolution during the last 5 to 10 years. Available randomized data currently support a role for chemotherapy as part of combined modality, curative treatment strategies in the management of patients with unresectable disease, advanced nasopharynx cancer, and as part of a larynx preservation approach in patients with advanced larynx or hypopharynx cancer requiring total laryngectomy. Chemoprevention as a strategy to prevent second primary tumors also shows great promise.

Antineoplastic Agents↗
PubMed1996

Outcomes research studies.

The outcomes movement has its roots in studies conducted in the 1970s and '80s, which showed that there was substantial geographic variability in medical practice in the United States and that such variability was driven by nonmedical factors. Outcomes management has several key components: the development and implementation of guidelines; measurement, pooling, and dissemination of clinical and outcomes data; and refinement of guidelines based on analysis of those data. Cancer has lagged behind many other areas of medicine in pursuing outcomes research and management. The National Comprehensive Cancer Network (NCCN) has made a commitment to perform outcomes research within its member institutions and has begun to pool and analyze selected patterns of care and outcomes data. The network's ultimate goal is the creation of a uniform outcomes measurement system to monitor guideline compliance.

Humans↗
PubMed1996

High-dose edatrexate with oral leucovorin rescue: a phase I and clinical pharmacological study in adults with advanced cancer.

Our objective was to determine the maximum tolerated dose and toxicity of i.v. edatrexate with p.o. leucovorin. Thirty-one adults with advanced solid tumors received edatrexate as a 2-h infusion, once a week for 3 weeks, recycled every 28 days. p.o. leucovorin (10 mg/m2, every 6 h for 10 doses) began 24 h later. All had urinary alkalinization and p.o. hydration. Nine dosage levels ranging from 120 to 3750 mg/m2 were explored. Fatigue, epistaxis, nausea/emesis, mucositis, rash, myalgias, leukopenia, thrombocytopenia, and transient elevations of serum aspartate transferase were observed. Leukoencephalopathy with clinical manifestations occurred in two patients (one had prior cranial irradiation). Pharmacokinetic studies carried out at the 120- and 1080-mg/m2 dose levels revealed no significant difference in the elimination half-life at the two dose levels studied and no significant intrapatient variability between day 1 and day 8 edatrexate administration. Serum edatrexate levels measured using a dihydrofolate reductase inhibition assay correlated with those by high-performance liquid chromatography. Three major and two minor antitumor responses occurred. The maximum tolerated dose was 3750 mg/m2, with grade 3 or 4 leukopenia (one patient), stomatitis (one patient), and leukoencephalopathy (one patient). Because of the occurrence of leukoencephalopathy, further study of high-dose edatrexate with leucovorin rescue is not recommended.

Administration, Oral↗
PubMed1995

Ifosfamide plus high-dose cisplatin in patients with non-small cell lung cancer previously treated with chemotherapy.

This study determined the maximum tolerated dose (MTD) of ifosfamide that could be given with high-dose cisplatin to non-small cell lung cancer (NSCLC) patients previously treated with non-platin-containing chemotherapy and to assess the efficacy of this combination. Twenty-three patients with inoperable NSCLC treated with one prior chemotherapy regimen received continuous infusion ifosfamide 1.2 g/m2 per day with MESNA for 5 days every 35 days and cisplatin 120 mg/m2. After one patient who received cisplatin as a single dose developed grade 4 nephrotoxicity and myelosuppression, cisplatin was given in four divided doses (30 mg/m2 per day) and the ifosfamide dose was lowered to 1.0 g/m2 per day, infused over 4 days. Dose-limiting grades 3 and 4 leukopenia was seen in 43%. A major objective response rate of 9% was observed. The 1-year survival was 30%, with a median survival of 6.4 months. The MTD of ifosfamide administered with cisplatin (30 mg/m2 per day for 4 consecutive days) to this population of patients is 1.0 g/m2 daily for 4 days. This combination produced limited anticancer activity and significant toxicity. Excessive toxicity was observed when cisplatin was given as a single dose with ifosfamide, and this schedule should not be used.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Chemotherapy for recurrent disease and combined modality therapies for head and neck cancer.

The identification and development of new agents and innovative treatment approaches remain a priority. The prognosis for patients with recurrent or metastatic head and neck cancer remains poor; thus participation in trials of promising investigational agents is an important option for these individuals. For patients with locally advanced tumors, combined modality treatment is undergoing rapid evolution. The optimal combination and sequence of therapies have yet to be determined. However, available data support an increasing role for chemotherapy especially as part of strategies to preserve organ function and treat unresectable disease.

Carcinoma, Squamous Cell↗
PubMed1995

Salvage laryngectomy for unsuccessful larynx preservation therapy.

From 1983 to 1991, 31 patients underwent salvage laryngectomy for persistent or recurrent squamous carcinoma of the larynx (14), hypopharynx (15), or oropharynx (2) as part of a larynx preservation protocol. Laryngectomy was performed as a consequence of poor response to induction chemotherapy in 13 and for recurrent disease after completion of chemotherapy and irradiation in 18. Postoperative pharyngocutaneous fistula occurred in 39%, resulting in prolonged hospitalization. Local control was achieved in 68%, more often in patients with laryngeal as opposed to nonlaryngeal primaries (86% versus 53%; p = .05). The overall actuarial survival and disease-specific survival at 2 years were 32% and 38%, respectively. Disease-specific survival at 2 years was better in patients with laryngeal as compared to nonlaryngeal primaries (56% versus 24%; p = .02). There were no long-term survivors among the nonlaryngeal primary patients. In selected patients in whom larynx preservation failed, salvage laryngectomy was associated with acceptable local control and survival. Palliation was obtained in patients who were not cured by their laryngectomy. Future investigation will focus on identification of factors predicting complications and strategies to reduce the incidence and severity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Organ-function preservation in advanced oropharynx cancer: results with induction chemotherapy and radiation.

PURPOSE: To evaluate the feasibility and efficacy of a strategy using induction chemotherapy followed by radiation therapy (RT) as a means of organ-function preservation in patients with advanced oropharynx cancer. PATIENTS AND METHODS: From January 1983 to December 1990, 33 patients with advanced squamous cell oropharynx cancer whose appropriate surgical management would have required a tongue procedure and potential total laryngectomy were treated with one to three cycles of cisplatin (CDDP)-based induction chemotherapy. Patients with a complete response (CR) or partial response (PR) at the primary site then received definitive external-beam RT with or without interstitial implant with or without neck dissection with surgery to the primary tumor site reserved for disease persistence or relapse; patients with less than a PR after chemotherapy had appropriate surgery and postoperative RT recommended. RESULTS: With a median follow-up period of 6.2 years, actuarial overall and failure-free survival rates at 5 years are 41% and 42%, respectively. Chemotherapy toxicity contributed to the death of two patients and was possibly a factor in two others. Local control was achieved in 14 patients (42%) without any surgery to the larynx or tongue. Among 13 patients currently alive, all had a preserved larynx and only one required tongue surgery; 12 of 13 have speech subjectively described as always understandable; and nine of 13 have no significant restrictions in their diet. CONCLUSION: This treatment program is feasible and effective in patients with advanced oropharynx cancer and produces an excellent functional outcome in most long-term survivors. Modifications to optimize patient selection, minimize toxicity, and improve local control are indicated. The relative toxicity, efficacy, and functional outcome provided by this and other chemotherapy and RT programs versus either standard surgery and/or RT options can only be addressed in a randomized comparison of these therapies.

Adult↗
PubMed1994

Cisplatin, fluorouracil, and leucovorin. Increased toxicity without improved response in squamous cell head and neck cancer.

OBJECTIVE: To evaluate the activity and toxicity of the drug combination cisplatin, fluorouracil by continuous infusion, and high-dose oral leucovorin calcium (PFL) as induction chemotherapy in patients with advanced and untreated squamous cell head and neck (SCHN) cancer. DESIGN: Nonrandomized, prospective trial. SETTING: Referral center (comprehensive cancer center). PATIENTS: Twenty-two patients with stage III (n = 7) and IV (n = 15) M0 SCHN cancer of the larynx (n = 13), hypopharynx (n = 7), and oropharynx (n = 2) whose standard treatment would have required total laryngectomy. INTERVENTIONS: Three cycles of PFL were administered prior to local-regional therapy (concomitant cisplatin and radiation and/or neck dissection, with total laryngectomy reserved for nonresponse or relapse). Chemotherapy included cisplatin (100 mg/m2) on day 1 by short intravenous infusion; fluorouracil (800 mg/m2) on days 1 through 5 by continuous infusion; and leucovorin (100 mg) every 4 hours by mouth for 30 doses. The PFL combination was administered every 21 days. MAIN OUTCOME MEASURES: Clinical response to chemotherapy and observed toxic effects during chemotherapy. RESULTS: Five patients were inevaluable for response, with three early deaths (infection in two and sudden death in one), one cerebrovascular accident, and one patient declining further chemotherapy. Of the remaining 17 patients, 10 had a major response to chemotherapy, but in only five patients (29%) was this complete (95% confidence interval, 8% to 51%). Other significant toxic effects included grade 3 to 4 mucositis in eight patients and grade 3 to 4 neutropenia in 10. CONCLUSIONS: While PFL is active in patients with SCHN cancer, we were unable to reproduce the high complete response rates reported by other centers. Its use can be associated with significant toxic effects. We do not recommend the use of PFL for the treatment of patients with SCHN cancer outside the context of a clinical trial until there is further critical assessment of its activity and toxicity.

Adult↗