Biomedical subjects
Publications and source records attributed to W J Moran.
Many years ago, planned giving was characterized as low key and troubled by a lack of closure. Today, planned giving officers are feeling the pressure that all fund raisers face for immediate fund-raising results and more aggressive fund-raising methods.
OBJECTIVE: To evaluate the use of endosseous transcutaneous implants to retain removable facial prostheses for the rehabilitation of orbital defects. SETTING: Tertiary referral center. PATIENTS: Six patients with a history of facial defects secondary to orbital exenteration for cancer ablation. OUTCOME MEASURES: Clinically noted functional and cosmetic results, patient reports of satisfaction, and complications encountered. RESULTS: Twenty-three of 25 implants were integrated (postoperative period, 13 to 65 months; mean, 44.2 months), representing an integration success rate of 92%. All patients were successfully wearing implant-retained prostheses after 48.3 months (post-prosthesis delivery period, 1 to 48.3 months; mean, 24.5 months). Overall patient satisfaction was very high. CONCLUSIONS: Implant-retained prosthetics represent a safe and effective treatment option. It is anticipated that this treatment will become the standard of rehabilitative care for patients with orbital defects.
PURPOSE: To determine survival rates and the pattern of failure in head and neck cancer patients treated with induction chemotherapy, limited surgery and concomitant chemoradiotherapy. PATIENTS AND METHODS: Three cycles of induction chemotherapy with cisplatin, fluorouracil (5-FU), leucovorin, and interferon alfa-2b (PFL-IFN) were followed by optional surgery, and seven or eight cycles of 5-FU, hydroxyurea, and concurrent radiation for 5 days (FHX) for a total radiation dose of 65 to 75 Gy. Surgical resection was performed with the intent to spare organ function. RESULTS: Seventy-one patients were treated at three institutions. Sixty-five patients (91%) had stage IV disease with N2/3 in 46. Thirty-three patients (51%; 95% confidence interval, 39% to 63%) achieved a clinical complete response (CR) to PFL-IFN. Local therapy consisted of surgery in 37 and/or FHX in 55 patients. With a median follow-up duration of 37 months, there have been 20 recurrences (15 local, four distant, and one both local and distant), and 29 deaths, 15 in patients with disease progression and 14 not directly related to the primary tumor. Four patients have developed second malignancies. At 3 years, 69% (+/- 6%) are progression-free and the overall survival rate is 60% (+/- 6%). Toxicity of PFL-IFN included severe or life-threatening mucositis (54%) and myelosuppression (60%). Five patients died of toxicity. During FHX, 70% of patients had grade 3 or 4 mucositis. CONCLUSION: PFL-IFN is highly active, producing clinical CRs in 51% of patients, and, when followed by FHX, resulting in high local and distant control and overall survival rates. Second malignancies and intercurrent medical disease emerge as major risks to long-term survival. In view of the high toxicity and long treatment duration, further modifications of this approach are required.
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Review of the otolaryngologic literature reveals no case reports of mycosis fungoides involving the esophagus. Post-mortem studies report 12 cases of esophageal involvement in 131 autopsies of patients with mycosis fungoides. We describe a 54-year-old man with mycosis fungoides involving the larynx, hypopharynx, and esophagus. Treatment consisted of radiation to this area, with resolution of the patient's hoarseness and dysphagia. The charts of 96 patients with mycosis fungoides treated at our institution were retrospectively reviewed. Three additional cases involving the aerodigestive tract, but not the esophagus, were found. Esophageal mycosis fungoides was an incidental finding in two of seven autopsies at our institution.
To increase the complete remission (CR) rate achieved with two cycles of cisplatin, continuous infusion fluorouracil (5-FU) and oral leucovorin (PFL) we added two antifolate drugs, methotrexate (MTX) and the lipophilic piritrexim (PTX), to the combination (PFL-MP). Twenty-eight patients with previously untreated Stage IV squamous cell carcinoma of the head and neck received 2 cycles of cisplatin 100 mg/m2 on day 1 followed by a 5-day continuous infusion of 5-FU at 800 mg/m2/day and 100 mg of leucovorin administered orally every 4 hours. MTX was administered at 40 mg/m2 IV on day 15 and PTX at 75 mg orally twice daily on days 22 to 26, with cycle 2 starting on day 36. After 2 of the first 5 patients had tumor progression between days 15 and 35, the regimen was intensified to MTX 50 mg/m2, PTX 100 mg twice daily and a cycle duration of 28 days. Local therapy consisted of surgery and/or radiotherapy with concomitant 5-FU and hydroxyurea (FHX) administered every other week. Eleven patients (39%, 95% confidence intervals 21-57%) had a CR, 9 (32%) had a PR, and four patients had no response. Four patients were unevaluable for response to PFL-MP. Patients with poor performance status or N3 disease were less likely to achieve a CR. Mucositis following PFL was the dose-limiting toxicity. Local therapy included surgery in 15 patients and FHX chemoradiotherapy in 19 patients. The administration of FHX in this setting proved feasible and the regimen was given near the intended dose intensity in the majority of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Concentrate on consistent donors and volunteers. Look for older individuals and pay special attention to those who have no direct heirs.
In planned giving, 80 percent of the money comes from bequests and 20 percent from life income agreements. But fund raisers still spend most of their time pursuing the 20 percent.
Two regimens of neoadjuvant chemotherapy for previously untreated patients with locally advanced head and neck cancer were compared with the goal of identifying a regimen with a greater than 50% complete response (CR) rate. Patients with a performance status of 0 to 2 and normal end-organ function were randomized to receive either four cycles of neoadjuvant methotrexate, cisplatin, and continuous infusion 5-fluorouracil (5-FU) (MPF) (arm A), or four cycles of bleomycin, cisplatin, and methotrexate (PBM) alternating with cisplatin and 5-FU (PF) (arm B). Patients with a performance status of greater than 2 or a carbon monoxide diffusion capacity of less than 50% of the predicted value were assigned to the arm A regimen but were analyzed separately (arm C). Local therapy consisted of surgery (for patients with resectable disease) or radiation therapy followed by two cycles of adjuvant chemotherapy with the regimen that was administered initially. Of the 42 patients who were evaluated, 16 were randomized to arm A, 13 to arm B, and 13 to arm C. The clinical CR rate was 19% on arm A (95% confidence interval, 0% to 38%), 39% on arm B (95% confidence interval, 12% to 66%) (P = 0.41), and 54% on arm C (95% confidence interval, 27% to 81%). At a median follow-up time of 35 months, the 2-year actuarial survival rate was 61% on arm A, 69% on arm B (the P value was not significant), and 38% on arm C. The 2-year survival rate for all 42 patients who were treated was 57% and the median survival time was 31 months. Toxicities of neoadjuvant chemotherapy on all arms consisted of mild to moderate myelosuppression and renal toxicity. The incidence of moderate to severe mucositis was significantly higher on arm A than arm B (P = 0.02). Two cycles of adjuvant chemotherapy were administered to only 11 of 42 patients due to patient refusal or cumulative toxicity. In conclusion, both neoadjuvant chemotherapy regimens resulted in similar response and survival rates, but mucositis was more severe with arm A. However, since neither regimen was likely to cause a CR rate of greater than 50%, this study was closed to further patient accrual.
The radiobiological parameters of 33 tumor cell lines were studied in biopsy samples obtained from patients prior to radiotherapy. Epithelial tumor cells derived from head and neck cancer patients were more radioresistant than tumor cell lines derived from patients with sarcoma regardless of method of analysis. The presence of radioresistant tumor cell lines was associated with local failure in some patients. However, the presence of radiosensitive tumor cells did not necessarily predict local control. Our data suggest radiocurability is complex and inherent radiobiological parameters of tumor cells may be only one factor in radiotherapy outcome.
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Hydroxyurea and fluorouracil (5-FU) are active cytotoxic drugs in head and neck cancer and have shown synergistic activity in vitro. Both drugs also act as radiosensitizers. Therefore, we administered radiotherapy at daily fractions of 180 to 200 cGy with simultaneous continuous infusion 5-FU at 800 mg/m2/d and escalating daily doses of hydroxyurea for five days. Cycles were repeated every other week until completion of radiotherapy. Thirty-nine inoperable patients were treated at six dose levels of hydroxyurea ranging from 500 mg to 3,000 mg orally daily. Little effect of hydroxyurea on the WBC or platelet count was noted in patients receiving less than 2,000 mg daily, whereas both parameters decreased progressively in patients receiving 2,000 mg daily or more. Mucositis occurred at all dose levels, requiring frequent dose reduction of 5-FU; however, in patients receiving a daily hydroxyurea dose of 2,000 mg or less, the median weekly 5-FU dose administered was 1,725 mg/m2 (86% of the intended 5-FU dose), whereas at daily hydroxyurea doses exceeding 2,000 mg, the median weekly 5-FU dose decreased to 1,133 mg/m2 (57%) (P = .001). Of 15 evaluable patients with recurrent disease after prior local therapy only one failed to respond; six had a complete response (CR), and eight a partial response (PR). Of 17 evaluable patients without prior local therapy, 12 had a CR, with no patient developing recurrence in the irradiated field to date; five patients had a PR. We conclude that the recommended dose of hydroxyurea in this regimen is 2,000 mg daily. That dose will cause mild to moderate myelosuppression and will allow for delivery of greater than 80% of the intended 5-FU dose. The activity of this regimen in poor-prognosis head and neck cancer exceeds 90%; its further investigation in previously untreated patients is warranted.
To increase the complete response (CR) rate of patients with locally advanced head and neck cancer after three cycles of neoadjuvant chemotherapy, we added sequential methotrexate to the combination of cisplatin and continuous infusion fluorouracil (5-FU). We also evaluated the feasibility of administering three additional cycles of the same regimen as adjuvant chemotherapy. Thirty-eight patients were treated; the median age was 53 years and 36 patients had stage IV disease. Chemotherapy consisted of methotrexate 120 mg/m2 followed 24 hours later by cisplatin 100 mg/m2 and a five-day continuous infusion of 5-FU at 1,000 mg/m2/d. Of 34 patients evaluable for response to neoadjuvant chemotherapy, nine had a CR, 21 a partial response (PR), two a minimal response (MR), and one patient each stable disease (SD) and no response (NR). Of 31 patients who received local therapy, 15 were treated with surgery and radiotherapy and 16 with radiotherapy alone. Of 25 patients eligible to receive adjuvant chemotherapy only ten received all three intended cycles, while 15 received less or no adjuvant chemotherapy because of patient refusal, cumulative toxicity, or early disease progression. With a median follow-up time of 39 months, the median survival is estimated to be 20 months. Of eight patients with nasopharyngeal or paranasal sinus cancer, none has had disease recurrence. Patients with good initial performance status and low N-stage also had a significant survival advantage. Chemotherapy-related toxicities consisted mainly of mucositis, requiring 5-FU dose reduction in the majority of patients; similar toxicities were exacerbated in the adjuvant setting. The addition of methotrexate did not increase the CR rate over what has been reported for the combination of cisplatin and 5-FU alone. Certain subsets of patients appear to have a good prognosis when treated in this fashion. The administration of adequate adjuvant chemotherapy in patients with head and neck cancer remains difficult due to toxicity and poor patient compliance.
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We tested the combination of hydroxyurea (HU), 5-fluorouracil (5-FU), and concomitant radiotherapy (XRT) in a group of patients with advanced or recurrent head and neck cancer. Both drugs are effective single agents, have shown synergistic activity in vitro, and can act as radiation sensitizers. A 5-day course of radiotherapy, with simultaneous HU and continuous infusion 5-FU, was followed by a 9-day rest period; cycles were repeated until completion of XRT. Sixteen patients have completed their therapy. Eleven patients had recurrent disease after previous therapy with surgery (11 patients), radiotherapy (9 patients), and combination chemotherapy (4 patients). Five patients had not received previous local therapy. These patients had persistent disease after induction chemotherapy and/or were inoperable because of poor general medical condition. Of 15 patients evaluable for response, 9 had complete response, including 5 patients who had earlier local therapy; 5 had partial response; and 1 failed to respond. Toxicities included mild myelosuppression and mucositis. No unusual complication related to previous radiotherapy was observed. This regimen has shown impressive activity in a cohort of patients who are not usually responsive to other types of currently available therapy. We are continuing our investigation to further define efficacy, toxicity, and maximally tolerated doses of this regimen.
As a result of prolonged hospitalizations and the frequent administration of sclerosing antibiotics and/or chemotherapeutic agents, vascular access frequently becomes difficult in patients with advanced head and neck carcinoma. Eighty-six totally implantable venous access devices were placed in 83 patients with advanced head and neck cancer to facilitate the administration of continuous intravenous infusion chemotherapy. Complications relating to surgical placement or usage of the device occurred in 29 of 86 ports (34%), leading to the removal of eight devices (9%). The implantation of two devices required revision. There were no serious sequelae from any of the complications. The port facilitated the administration of home chemotherapy in 11 patients. Because of our favorable experience, we now routinely recommend placement of these devices to all patients with advanced head and neck cancer at our institution.
We added high-dose oral leucovorin to the combination of cisplatin and fluorouracil (5-FU) to assess the efficacy of this regimen in the treatment of patients with head and neck cancer. Cisplatin, 100 mg/m2, was followed by a 5-FU continuous infusion at 600 mg/m2/d for five days. Leucovorin, 50 mg/m2, was administered at the start of cisplatin and every six hours throughout the duration of the 5-FU infusion. The dose of 5-FU was escalated to 800 mg/m2 and 1,000 mg/m2 according to observed toxicity. In a second phase of the study, the dose of leucovorin was escalated to 50 mg/m2 every four hours. A total of 25 patients were registered: 23 had recurrent disease after extensive prior treatment; and two had newly diagnosed metastatic disease. The maximally tolerated dose of 5-FU was 800 mg/m2/d with leucovorin administered every six hours. Toxicities at that level included mild to moderate myelosuppression and dose-limiting mucositis in the previously irradiated field. Identical toxicities were observed when administering 800 mg/m2/d of 5-FU with leucovorin every four hours. Eighteen patients were evaluated for response: one had a pathologic complete response; nine had a partial response (including four who received prior cisplatin and 5-FU as induction chemotherapy); and eight patients failed to respond. The mean peak and trough plasma leucovorin concentrations were 2.61 (+/- 1.07) mumol/L and 2.46 (+/- 0.95) mumol/L with administration of the drug every six hours, and 2.75 (+/- 2.15) mumol/L and 2.52 (+/- 1.48) mumol/L with administration every four hours. We conclude that the combination of cisplatin, 5-FU, and leucovorin has activity in the treatment of recurrent head and neck cancer. The maximally tolerated dose of 5-FU in this study was 800 mg/m2/d, with mucositis in previously irradiated sites being dose-limiting. Plasma leucovorin concentrations exceeding 1 mumol/L are achieved following oral administration of this drug.