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L D Wilson

Publications and source records attributed to L D Wilson.

At least 19 recordsLinked to original sources
PubMed2005

Developmentally regulated expression of the regulator of G-protein signaling gene 2 (Rgs2) in the embryonic mouse pituitary.

During the development of the anterior pituitary gland, five distinct hormone-producing cell types emerge in a spatially and temporally regulated pattern from an invagination of oral ectoderm termed Rathke's Pouch. Evidence from mouse knockout and ectopic expression studies indicates that 12.5 days post coitum (dpc) to 14.5 dpc is a critical period for the expansion of the progenitor cell pool and the determination of most hormone-secreting cell types. While signaling proteins and transcription factors have been identified as having key roles in pituitary cell differentiation, little is known about the identity and function of proteins that mediate signal transduction in progenitor cells. To identify genes that are enriched in the embryonic pituitary gland, we compared gene expression in 14.5 dpc pituitary and 14.5 dpc embryo minus pituitary tissues using the NIA 15K microarray. Analysis of the data using the R program revealed that the Regulator of G Protein Signaling 2 (Rgs2) gene was 3.9-fold more abundant in the 14.5 dpc pituitary. In situ hybridisation confirmed this finding, and showed that Rgs2 expression in midline tissues was restricted to the pituitary and discrete regions of the nervous system. Within the pituitary, Rgs2 was expressed in undifferentiated cells, and was downregulated at the completion of the hormone cell differentiation. To investigate Rgs2 function in the pituitary, we examined hormone cell differentiation in Rgs2 null neonate mice. Pituitary cell differentiation and morphology appeared normal in the Rgs2 mutant animals, suggesting that other Rgs family members with similar activities may be present in the developing pituitary.

Animals↗
PubMed2004

Cisplatin, fluorouracil, and leucovorin induction chemotherapy followed by concurrent cisplatin chemoradiotherapy for organ preservation and cure in patients with advanced head and neck cancer: long-term follow-up.

PURPOSE: The poor functional outcome in patients with advanced head and neck squamous cell carcinoma (HNSCC) with surgery and radiation has led to alternative approaches to advanced disease. We conducted a phase II study of induction chemotherapy followed by concurrent chemoradiotherapy for organ preservation in patients with advanced resectable and unresectable (nasopharyngeal) tumors. PATIENTS AND METHODS: Forty-two patients with stage III to IV resectable HNSCC and nasopharyngeal tumors received induction chemotherapy with two courses of cisplatin (20 mg/m2/d continuous infusion [CI]), fluorouracil (800 mg/m2/d CI), and leucovorin (500 mg/m2/d CI; PFL) for 4 days followed by concurrent therapy with cisplatin (100 mg/m2/d on days 1 and 22) and approximately 70 Gy of external-beam radiotherapy. RESULTS: Response to induction chemotherapy included partial response rate of 52% and complete response rate of 24%. The most common grade 3 or 4 toxicity was neutropenia (59%). After cisplatin chemoradiotherapy the complete response rate was 67%. Toxicities of cisplatin chemoradiotherapy consisted of grade 3 or 4 mucositis (79%) and neutropenia (51%). At a median follow-up of 71.5 months, 43% of the patients are still alive and disease-free. The 5-year progression-free survival (PFS) rate was 60%, and the 2- and 5-year overall survival (OS) rates were 67% and 52%, respectively. Three patients died of second primaries. Late complications of treatment included xerostomia and hoarseness. One patient had persistent dysphagia and required laser epiglotectomy 108 months after treatment. CONCLUSION: Induction chemotherapy with PFL followed by concurrent cisplatin chemoradiotherapy is well tolerated and results in a good likelihood of organ preservation and excellent PFS and OS.

Adolescent↗
PubMed2004

A critical role for the parabrachial nucleus in generating central nervous system responses elicited by a systemic immune challenge.

Using Fos immunolabelling as a marker of neuronal activation, we investigated the role of the parabrachial nucleus in generating central neuronal responses to the systemic administration of the proinflammatory cytokine interleukin-1beta (1 microg/kg, i.a.). Relative to intact animals, parabrachial nucleus lesions significantly reduced the number of Fos-positive cells observed in the central amygdala (CeA), the bed nucleus of the stria terminalis (BNST), and the ventrolateral medulla (VLM) after systemic interleukin-1beta. In a subsequent experiment in which animals received parabrachial-directed deposits of a retrograde tracer, it was found that many neurons located in the nucleus tractus solitarius (NTS) and the VLM neurons were both retrogradely labelled and Fos-positive after interleukin-1beta administration. These results suggest that the parabrachial nucleus plays a critical role in interleukin-1beta-induced Fos expression in CeA, BNST and VLM neurons and that neurons of the NTS and VLM may serve to trigger or at least influence changes in parabrachial nucleus activity that follows systemic interleukin-1beta administration.

Animals↗
PubMed2001

The Legs For Life Screening for Peripheral Vascular Disease: results of a prospective study designed to improve patient compliance with physician recommendations.

PURPOSE: To determine how compliance with recommendations made by physicians during the 2000 Legs For Life National Screening for Peripheral Vascular Disease (PVD) and Leg Pain is affected through the use of (i) simple and concise patient information and recommendation cards and (ii) a "targeted" postscreening follow-up plan. MATERIALS AND METHODS: Patients were initially screened for PVD by completion of the Legs For Life Risk Factor Assessment form and determination of bilateral ankle/brachial indexes (ABIs). Each patient then met with an interventional radiologist or vascular surgeon. Patients with normal ABIs (>1.0 bilaterally) or mildly abnormal ABIs (<1.0 but >0.90) were classified as having no risk and low risk, respectively. Patients with ABIs of 0.70-0.89 were classified as having moderate risk for PVD and patients with ABIs <0.69 were classified as having high risk for PVD. Physicians reviewed the Risk Factor Assessment form with each patient and made specific lifestyle improvement recommendations. For the year 2000 screening, patients classified at moderate and high risk for PVD received special instructions and a card containing clearly printed information on the purpose of the Legs For Life screening, their level of risk for PVD, specific recommendations for follow-up, and phone numbers to call to help arrange for that follow-up. Two weeks after the screening, a second copy of this card was mailed to each moderate- and high-risk assessed patient. Four months later, each of these patients was contacted by telephone to determine if they had pursued additional care or testing. RESULTS: A total of 185 patients were screened, 42 (23%) of whom were determined to be at moderate or high risk for PVD. Four months after the screening, 39 (93%) of these patients were available for follow-up. Twenty (51%) patients had received no further medical advice or treatment. Nineteen (49%) patients had pursued further medical care which included physician consultation (n = 19; 100%), noninvasive Doppler evaluation (n = 10; 26%), diagnostic arteriography (n = 2; 5%), initiation of pharmacologic therapy for claudication (n = 1; 3%), percutaneous intervention (n = 1; 3%), or vascular surgery (n = 1; 3%). Seventeen of 39 patients (44%) reported that claudication-type leg pain was still a concern and/or lifestyle-limiting problem. CONCLUSION: Patients can be provided with problem-focused information and succinct physician recommendations at and soon after a screening for PVD, which can contribute to enhanced patient compliance. However, a host of personal, social, health, and physician-related issues still prevent a large percentage of patients from achieving relief of PVD-associated leg pain.

Adult↗
PubMed2001

Cocaine, ethanol, and cocaethylene cardiotoxity in an animal model of cocaine and ethanol abuse.

OBJECTIVES: Simultaneous abuse of cocaine and ethanol affects 12 million Americans annually. In combination, these substances are substantially more toxic than either drug alone. Their combined cardiac toxicity may be due to independent effects of each drug; however, they may also be due to cocaethylene (CE), a cocaine metabolite formed only in the presence of ethanol. The purpose of this study was to delineate the role of CE in the combined cardiotoxicity of cocaine and ethanol in a model simulating their abuse. METHODS: Twenty-three dogs were randomized to receive either 1) three intravenous (IV) boluses of cocaine 7.5 mg/kg with ethanol (1 g/kg) as an IV infusion (C+E, n = 8), 2) three cocaine boluses only (C, n = 6), 3) ethanol infusion only (E, n = 5), or 4) placebo boluses and infusion (n = 4). Hemodynamic measurements, electrocardiograms, and serum drug concentrations were obtained at baseline, and then at fixed time intervals after each drug was administered. RESULTS: Two of eight dogs in the C+E group experienced cardiovascular collapse. The most dramatic hemodynamic changes occurred after each cocaine bolus in the C+E and C only groups; however, persistent hemodynamic changes occurred in the C+E group. Peak CE levels were associated with a 45% (SD +/- 22%, 95% CI = 22% to 69%) decrease in cardiac output (p < 0.05), a 56% (SD +/- 23%, 95% CI = 32% to 80%) decrease in dP/dt(max) (p <.006), and a 23% (SD +/- 15%, 95% CI = 7% to 49%) decrease in SVO(2) (p < 0.025). Ventricular arrhythmias were primarily observed in the C+E group, in which four of eight dogs experienced ventricular tachycardia. CONCLUSIONS: Cocaine and ethanol in combination were more toxic than either substance alone. Co-administration resulted in prolonged cardiac toxicity and was dysrhythmogenic. Peak serum cocaethylene concentrations were associated with prolonged myocardial depression.

Alcoholism↗
PubMed2000

Prognostic significance of cyclin D1 protein levels in early-stage larynx cancer treated with primary radiation.

Recent laboratory experiments have demonstrated that cyclin D1 levels (cycD1) can influence radiosensitivity. The purpose of the current study is to evaluate the prognostic significance of cycD1 for local recurrence in early-stage larynx cancer treated with primary radiation therapy. The study was conducted using a matched case-control design in 60 early-stage (T1-T2/N0) larynx cancer patients. All patients had squamous cell carcinoma of the larynx and were treated with primary radiation to a total median dose of 66 Gy in daily fractions of 2 Gy, without surgery or chemotherapy. Thirty patients who suffered a local relapse in the larynx after treatment served as the index case population. These 30 cases were matched by age, sex, site (glottic vs. supraglottic), radiation therapy technique/dose, and follow-up, to 30 control patients who did not experience a local relapse. Immunohistochemical staining from cycD1 was performed on the paraffin-embedded specimens. The pathologist, blinded to the clinical information, scored each of the specimens on a four-point intensity scale (0 = no stain, 1 = faint, 2 = moderate, 3 = strong) and percent distribution. Patients were considered to be positive for cyclin D1 if the staining was 2+ or greater with a percent distribution of at least 5%. By design of the study, the two groups were evenly balanced with respect to age, sex, stage, radiation dose, and follow-up. CycD1 levels correlated with proliferating cell nuclear antigen levels. Low levels of cycD1 significantly correlated with local relapse; 19/30 (63%) of the index cases stained negative, while only 10/30 (33%) of the control cases stained negative (P = 0.03). These data suggest that low levels of cycD1 correlate with relatively radioresistant early-stage larynx carcinoma. With larger more confirmatory clinical and laboratory data, this data may have significant clinical implications. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 22-28 (2000).

Carcinoma, Squamous Cell↗
PubMed2000

PSA based review of adjuvant and salvage radiation therapy vs. observation in postoperative prostate cancer patients.

Because of the uncertainties regarding the efficacy of postoperative radiation therapy for early prostate cancer, treatment strategies following radical prostatectomy include: (1) observation alone in high-risk patients, (2) adjuvant radiation therapy (PSA undetectable) in high-risk patients, or (3) salvage radiation therapy for biochemical and clinical recurrence. Fifty-two patients treated with postoperative radiation therapy in either an adjuvant setting (13) or for salvage (39) were retrospectively reviewed. The actuarial biochemical disease-free survival (bNED) rates following radiation therapy were calculated using the life-table method. Univariate and multi variate analyses were used to define the clinical factors that predict biochemical failure following postoperative radiation therapy. In addition, the bNED survival rate for 36 high-risk surgery patients who were simply observed following prostatectomy was determined. The 3-year bNED survival rate for the adjuvant radiation group was 85% compared with 27% for salvage radiation and 43% for the observation group. These results are statistically significant. Factors that predict biochemical failure following postoperative radiation therapy include preoperative PSA level, pre-radiation therapy PSA level, and seminal vesicle involvement. At our institutions, adjuvant radiation therapy was a superior strategy compared with either observation alone or salvage radiation therapy for high-risk postoperative prostate cancer patients. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 29-36 (2000).

Aged↗
PubMed2000

Experience with total skin electron beam therapy in combination with extracorporeal photopheresis in the management of patients with erythrodermic (T4) mycosis fungoides.

OBJECTIVE: We compared the prognosis of patients with erythrodermic mycosis fungoides (MF) administered total skin electron beam radiation (TSEB) plus neoadjuvant, concurrent, and adjuvant extracorporeal photopheresis (ECP) with the prognosis of patients administered only TSEB. Outcomes of clinical interest include disease-free survival (DFS), progression-free survival (PFS), overall survival (OS), and cause-specific survival (CSS). METHODS: This study was a retrospective nonrandomized series. Between 1974 and 1997, a total of 44 patients with erythrodermic MF from the Department of Therapeutic Radiology, Yale University School of Medicine, and the Department of Radiation Oncology, Cancer Care Ontario, Hamilton, Ontario, were collected and analyzed as a group (Hamilton = 15, Yale = 29). These patients received TSEB consisting of 32 to 40 Gy via 4 to 6 MeV. Twenty-one patients at Yale also received ECP treatment 2 days per month for a median of 6 months. Median age was 68 years (range, 29-82 years) at the commencement of TSEB, and 66% were male. Seventy-three percent of patients had received other therapies before TSEB, including 75 courses that failed to control disease (n = 15 systemic therapy, 16 biologicals, and 44 topical therapies). At TSEB, 59% had hematologic involvement (B1), 30% were stage IVA (N3), and 13% were IVB (M1). Median follow-up was 2.2 years (range, 0.3-13.9 years) subsequent to TSEB and 3.7 years from diagnosis (range, 0.8-16.8 years). RESULTS: All patients responded to TSEB within 2 months of completion, with a cutaneous complete response rate of 73%. For the 32 complete responders the 3-year DFS was 63%. It was 49% for those 17 patients who received only TSEB compared with 81% for those 15 patients who received TSEB + ECP. Cox regression analysis demonstrated that ECP was associated with prolonged remission (DFS multivariate P =.024, adjusting for B1 and stage). The 2-year PFS, CSS, and OS for the TSEB group were 36%, 69%, and 63%, respectively, compared with 66%, 100%, and 88% for the TSEB + ECP cohort. Cox regression demonstrated that ECP was associated with CSS (multivariate P =.048, adjusting for B1 and stage). For those who progressed, a total of 49 subsequent courses of therapy were administered (n = 20 chemotherapy, 10 biologicals, and 19 topical therapies). Thirteen patients died from MF-related causes, and 8 died from other causes. Acute and chronic toxicities were consistent with those previously reported. CONCLUSION: ECP given concurrently with, or immediately after, TSEB (32-40 Gy) significantly improves both PFS and CSS for patients with erythrodermic MF compared with TSEB without the addition of ECP.

Adult↗
PubMed2000

Tolerance develops to the sympathomimetic but not the local anesthetic effects of cocaine.

OBJECTIVES: The cardiovascular effects of cocaine are complex and include sympathomimetic as well as local anesthetic effects. The aim of the present study was to delineate cocaine toxicity in a model simulating cocaine binging patterns. DESIGN: Prospective laboratory investigation. Twelve dogs were randomized to receive 6 intravenous boluses of cocaine 5.25 mg/kg (high dose, n = 5), 3.5 mg/kg (low dose, n = 4), or placebo (n = 3) at 15-minute intervals. Arterial pressure, electrocardiogram, and serum cocaine were measured at control, then at fixed time intervals after each bolus of cocaine or placebo. Statistical significance was determined by ANOVA. RESULTS: Peak serum cocaine concentrations were 3500 ng/mL and 2167 ng/mL in the high- and low-dose groups. There were progressive decreases in mean arterial pressure in the high-dose cocaine group by as much as 32% (p = .003) after each cocaine bolus. However, in the low-dose group, increases in mean arterial pressure were observed after the initial cocaine boluses by as much as 31% (p = .013). Significant QRS prolongation was observed in both the high- and low-dose cocaine groups by as much as 65% (p < .001) and 10% (p < .03), respectively. However, the prolongation observed in the high-dose group was more pronounced and cumulative, while in the low-dose group the prolongation was transient. CONCLUSIONS: At low doses, cocaine's sympathomimetic properties predominate but tolerance develops. At high doses, cocaine's local anesthetic properties predominate, become more pronounced with repeated administration, and may have implications for cocaine-related dysrhythmias, cardiovascular collapse, and sudden death.

Analysis of Variance↗
PubMed1999

Total skin electron radiation for patients with erythrodermic cutaneous T-cell lymphoma (mycosis fungoides and the Sézary syndrome).

BACKGROUND: There is limited published evidence regarding the efficacy of total skin electron beam radiation for patients with the diffuse erythrodermic form of mycosis fungoides. METHODS: Forty-five patients with erythrodermic mycosis fungoides were managed at McMaster University in Hamilton, Ontario, Canada (n=34), and at Yale University (n=11) between 1970 and 1996. All received radiation without neoadjuvant, concomitant, or adjuvant therapies. The median age was 67 years (range, 42-84 years). The male-to-female ratio was 2.2. Fifteen received radiation for the treatment of newly diagnosed disease. There were 28 with Stage III (T4 N0-1 M0), 13 with Stage IVA (T4 N2-3 M0), and 4 with Stage IVB (T4 N0-3 M1) disease, and 21 had blood involvement. The median radiation dose was 32 gray (Gy) (range, 4.8-40 Gy). The median treatment time was 21 days (range, 3-125 days). A technically more intense method of radiation (32-40 Gy and 4-6 MeV electrons) was administered to 23 patients. RESULTS: All patients responded. The rate of complete cutaneous remission was 60%, with 26% remaining progression free at 5 years. Remission was associated with more intense radiation (P=0.014 in multivariate analysis with adjustment for blood and staging information). With the more intense radiation, 74% attained remission, with 36% remaining progression free at 5 years. For 8 patients with Stage III disease without blood involvement, all entered remission, with 69% remaining progression free at 5 years. Twenty of 30 deaths were related to mycosis fungoides. The median overall survival was 3.4 years, with a 10-year estimate of 28%. The median cause specific survival was 5 years, with a 10-year estimate of 43%. Both overall and cause specific survival were associated with an absence of blood involvement (both P<0.03 in multivariate analysis). Age was not a significant factor. Toxicities of radiation were acceptable when radiation was administered over 6-9 weeks at 5 fractions per week. CONCLUSIONS: Total skin radiation is an efficient monotherapy for patients with erythrodermic mycosis fungoides. With more intense radiation, the rate of cutaneous remission is 74%, and 27% remain progression free at 10 years. Radiation may be most efficacious in Stage III, with no blood involvement. When there is blood, lymph node, or visceral involvement, combined modality therapies should be explored.

Adult↗
PubMed1998

Local superficial radiotherapy in the management of minimal stage IA cutaneous T-cell lymphoma (Mycosis Fungoides).

PURPOSE: To evaluate the impact of local superficial radiotherapy with respect to local control, survival, and toxicity for patients with "minimal" stage IA cutaneous T-cell lymphoma (Mycosis Fungoides). METHODS AND MATERIALS: Between 1954 and 1996 a total of 21 patients were identified as receiving curative local superficial radiation (LSR) for minimal stage IA Mycosis Fungoides. All patients had pathologic documentation at diagnosis and at the time of suspected recurrences and no patient received prior radiation. Ten patients were treated with 100-280 Kv (A1), and 11 with 4-12 Mev electrons. Nine patients had failed prior therapies (steroids: 4; PUVA: 3; BCNU: 1; UVB: 1) and six received adjuvant therapy after completion of LSR (PUVA: 5; steroids: 1). Minimum follow-up was 1 year. RESULTS: The median follow-up was 36 months (13-246), and the median age when commencing LSR was 55 years (27-73). All patients were Caucasian, and 11 were male. A total of 32 lesions were identified in 21 patients; 13 patients had unilesional disease, 5 patients had 2 lesions, and 3 had 3 lesions. A total of 33 fields were treated with a median treatment surface area of 107 cm2 (11-785). The median surface dose was 20 Gy (6-40), with 17 patients receiving a dose > or = 20 Gy. The median fraction number was 5 for all fields, but was 10 for the fields receiving 20-40 Gy. The complete response rate was 97%, and all patients were alive at last evaluation. All failures were cutaneous. One patient had persistent disease (treated with 6 Gy), and three failed locally at 52 months (8 Gy), 16 months (20 Gy), and 4 months (20 Gy). None of these patients received adjuvant therapy. Two patients failed in distant skin sites and were salvaged. The actuarial DFS for the entire group at 5 and 10 years was 75 and 64%, respectively, with local control of 75% at both time intervals. For the 13 patients with unilesional disease, the DFS was 85% at 10 years. For those treated with doses > or = 20 Gy, the DFS was 91% as was local control (no distant failures). Toxicity included mild erythema and dry desquamation acutely. Chronic toxicity included dermatitis [2], and telangiectasia [1]. No second cutaneous malignancies or hematologic toxicity was noted. CONCLUSION: Patients with minimal Stage IA Mycosis Fungoides may be managed effectively with local superficial radiation alone without adjuvant therapy. Distant failure is unusual and patients should receive a minimum surface dose of 20 Gy, which offers excellent local control. Sequalae of therapy are minimal.

Adult↗
PubMed1998

Effective treatment of stage I uterine papillary serous carcinoma with high dose-rate vaginal apex radiation (192Ir) and chemotherapy.

PURPOSE: Uterine papillary serous carcinoma (UPSC) is a morphologically distinct variant of endometrial carcinoma that is associated with a poor prognosis, high recurrence rate, frequent clinical understaging, and poor response to salvage treatment. We retrospectively analyzed local control, actuarial overall survival (OS), actuarial disease-free survival (DFS), salvage rate, and complications for patients with Federation International of Gynecology and Obstetrics (FIGO) (1988) Stage I UPSC. METHODS AND MATERIALS: This retrospective analysis describes 38 patients with FIGO Stage I UPSC who were treated with the combinations of radiation therapy, chemotherapy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy (TAH/BSO), with or without a surgical staging procedure. Twenty of 38 patients were treated with a combination of low dose-rate (LDR) uterine/vaginal brachytherapy using 226Ra or 137Cs and conventional whole-abdomen radiation therapy (WART) or whole-pelvic radiation therapy (WPRT). Of 20 patients (10%) in this treatment group, 2 received cisplatin chemotherapy. Eighteen patients were treated with high dose-rate (HDR) vaginal apex brachytherapy using 192Ir with an afterloading device and cisplatin, doxorubicin, and cyclophosphamide (CAP) chemotherapy (5 of 18 patients). Only 6 of 20 UPSC patients treated with combination LDR uterine/vaginal brachytherapy and conventional external beam radiotherapy underwent complete surgical staging, consisting of TAH/BSO, pelvic/para-aortic lymph node sampling, omentectomy, and peritoneal fluid analysis, compared to 15 of 18 patients treated with HDR vaginal apex brachytherapy. RESULTS: The 5-year actuarial OS for patients with complete surgical staging and adjuvant radiation/chemotherapy treatment was 100% vs. 61% for patients without complete staging (p = 0.002). The 5-year actuarial OS for all Stage I UPSC patients treated with postoperative HDR vaginal apex brachytherapy and systemic chemotherapy was 94% (18 patients). The 5-year actuarial OS for Stage I UPSC patients treated with HDR vaginal apex brachytherapy and chemotherapy who underwent complete surgical staging was 100% (15 patients). The 5-year actuarial OS for the 20 Stage I UPSC patients treated with combinations of pre- and postoperative LDR brachytherapy and postop WART was 65%. None of the 6 surgically staged UPSC patients treated with LDR radiation and WART/WPRT developed recurrent disease. For patients with FIGO Stage IA, IB, and IC UPSC who underwent complete surgical staging, the 5-year actuarial DFS by depth of myometrial invasion was 100, 71, and 40%, respectively (p = 0.006). The overall salvage rate for local and distant recurrence was 0%. Complications following HDR vaginal apex brachytherapy included only Radiation Therapy Oncology Group (RTOG) grade 1 and 2 toxicity in 16% of patients. However, complications from patients treated with WART/WPRT, and/or LDR brachytherapy, included RTOG grade 3 and 4 toxicity in 15% of patients. CONCLUSION: Patients with UPSC should undergo complete surgical staging, and completely surgically staged FIGO Stage I UPSC patients can be effectively and safely treated with HDR vaginal apex brachytherapy and chemotherapy. Both OS and DFS of patients with UPSC are dependent on depth of myometrial invasion. The salvage rate for both local and distant UPSC recurrences is extremely poor. Complications from HDR vaginal apex brachytherapy were minimal.

Adult↗
PubMed1998

Intraoperative brachytherapy, laryngopharyngoesophagectomy, and gastric transposition for patients with recurrent hypopharyngeal and cervical esophageal carcinoma.

OBJECTIVE: To evaluate the role of laryngopharyngoesophagectomy (LPE), intraoperative 125I brachytherapy (IOBT), and gastric transposition (GT) in patients with recurrent carcinoma involving the hypopharynx, or cervical esophagus. METHODS: Between 1988 and 1994 a total of 21 patients were managed with LPE/IOBT/GT. All patients had documentation of recurrent disease at the hypopharynx or cervical esophagus and had previously been treated with external-beam radiation (EBRT) to a total median dose of 60 Gy. Median age was 67 years, with 17 male patients and four female. IOBT was performed in all cases with permanent 125I implantation. Medical records were retrospectively reviewed. Overall survival, local control, and complications were evaluated. Median follow-up was 6 months. RESULTS: The median activity of 125I was 36 mCi, with a median dose of 80 Gy to the region at risk. Fifteen patients had lymph node dissections performed in conjunction with LPE, and 10 patients had nodal involvement on pathologic examination. Margins were microscopically positive in nine patients, and lymphvascular space invasion noted in 13. Actuarial survival at 1 and 3 years was 32% and 14%, respectively, with patients alive and with local control at 6, 24, 36, and 48 months (negative margins). Actuarial local control at 1 and 3 years was 63%. Complications included fistula in five patients, facial edema in four, protracted facial pain in two, cervical abscess in one, and mucosal hemorrhage in one. CONCLUSION: Patients with recurrent carcinoma of the hypopharynx or cervical esophagus after EBRT have an extremely poor prognosis. LPE, IOBT, and GT may provide very good local control for all candidates and prolonged survival for a small percentage of patients with an acceptable risk profile.

Adult↗
PubMed1997

Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-A light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides).

PURPOSE: Patients with mycosis fungoides [cutaneous T-cell lymphoma (CTCL)] may benefit from adjuvant therapy after completing total skin electron beam therapy (TSEBT). We report the results for T1/T2 CTCL patients treated with adjuvant oral psoralen plus ultraviolet light (PUVA) with respect to overall survival (OS), disease-free survival (DFS), salvage of recurrence, and toxicity. METHODS AND MATERIALS: Between 1974 and 1993, TSEBT was administered to a total of 213 patients with CTCL. Records were reviewed retrospectively, and a total of 114 patients were identified as having T1 or T2 disease. Radiotherapy was provided via a 6-MeV linac to a total of 36 Gy, 1 Gy/day, 4 days/week, for 9 weeks. Beginning in 1988, patients were offered adjuvant PUVA within 2 months of completing TSEBT. This was started at 0.5-2 J/m2, 1-2 treatments/week, with a taper over 3-6 months. Therapy then continued once per month. There were 39 T1 and 75 T2 patients. Six T1 (15%) and eight T2 (11%) patients were treated with adjuvant PUVA. A further 49% of the 114 patients received adjuvant systemic therapy, 3% received spot external beam, 4% received adjuvant ECP, 2% received topical nitrogen mustard, 22% received a combination of therapies exclusive of PUVA, and 9% received no adjuvant therapy. Patients were balanced in all subgroups based on pre-TSEBT therapy. The median age of the cohort was 58 (range 20-88), with a median follow-up time of 62 months (range 3-179). RESULTS: Within 1 month after completing of TSEBT, 97% of T1, and 87% of T2 patients had achieved a complete remission. Stratified by adjuvant therapy, none of six T1 and one of eight T2 patients who received adjuvant PUVA failed within the first 3 years after completion of TSEBT. A total of 43% of the T1 and T2 patients receiving other or no adjuvant treatment failed within the same time course. The 5-year OS for the entire cohort was 85%. Those who received PUVA had a 5-year OS of 100% versus a 5-year OS for the non-PUVA group of 82% (p < 0.10). The 5-year DFS for the entire cohort was 53%. Those who received PUVA had a 5-year DFS of 85% versus a 5-year DFS for the non-PUVA group of 50% (p < 0.02). By T stage, those with T1 receiving PUVA exhibited no relapses, whereas those with T1 not treated with PUVA had a crude relapse rate of 36%. Median DFS was not reached at 103 months for the T1 adjuvant PUVA patients versus 66 months for the non-PUVA patients (p < 0.01). For those with T2, crude relapse rates were 25% and 55%, respectively, with DFS of 60 (median DFS not reached) and 20 months (p < 0.03). The 5-year DFS for patients salvaged with PUVA was 50%. Toxicity of adjuvant and salvage PUVA therapy was acceptable, with only two patients requiring a reduction in PUVA dosage. CONCLUSION: PUVA can maintain remissions in patients with CTCL after TSEBT. There is a significant benefit in DFS but no statistically significant improvement in OS. Prospective, randomized data are needed to confirm these results. PUVA is also effective as a salvage therapy after TSEBT in early-stage patients with recurrence, with acceptable toxicity.

Administration, Oral↗
PubMed1997

Bioreductive alkylating agent porfiromycin in combination with radiation therapy for the management of squamous cell carcinoma of the head and neck.

Porfiromycin (methyl mitomycin C) has been shown in laboratory studies to have increased preferential cytotoxicity to hypoxic cells and therefore may provide enhanced therapeutic efficacy over mitomycin C when used in combination with radiation therapy (RT). The purpose of the two clinical studies reported here is to evaluate the concomitant use of porfiromycin with RT in the management of squamous cell carcinoma of the head and neck. Between October 1989 and July 1992, 21 patients presenting with locally advanced stage III/IV squamous cell carcinoma of the head and neck were entered into a phase I toxicity trial evaluating porfiromycin as an adjunct to RT. Patients were eligible if they had biopsy documented squamous cell carcinoma of the head and neck with a low probability of cure by conventional means. Patients were treated with standard fractionated daily RT to a total median dose of 63 Gy, with porfiromycin administered on days 5 and 47 of the course of RT. Upon completion of this phase I trial, a phase III trial was initiated in November 1992 randomizing patients with squamous cell carcinoma of the head and neck to RT with mitomycin C vs. RT with porfiromycin. There is no radiation only arm in this current trial. To date, 75 patients have been entered on this trial and acute toxicity data are available on 67 patients (34 porfiromycin, 31 mitomycin C) who have completed their entire course of treatment. Median follow-up of the 21 patients enrolled in the phase I porfiromycin trial is 58.5 months. Of the 21 patients, 5 were treated at a dose of 50 mg/M2, 4 at 45 mg/M2, and the final 12 at 40 mg/M2, which appeared to result in acceptable acute hematological and nonhematological toxicities. As of December 1995, 14 of the 21 patients have died with disease and 7 remain alive and free of disease, resulting in a 5-year actuarial survival of 32%. Of the patients enrolled to date in the phase III randomized trial of mitomycin C vs. porfiromycin, there have been no statistically significant differences between the two arms with respect to white blood cell count (WBC), platelet, or hemoglobin nadirs. Acute nonhematological toxicities including mucositis, epidermitis, odynophagia, and nausea have also been comparable. Two patients in this current randomized trial died during treatment, apparently of nondrug-related causes. We conclude that the bioreductive alkylating agent porfiromycin has demonstrated an acceptable toxicity profile to date. Final analysis of the phase I trial, which revealed a 5-year no evidence of disease survival rate of 32% in patients with locally advanced disease and a low probability of cure, appears encouraging. We anticipate completion of the current ongoing trial comparing mitomycin C to porfiromycin in the next 2 years. Further investigations, including large-scale multiinstitutional trials employing bioreductive alkylating agents or other hypoxic cell cytotoxins as adjuncts to RT, are warranted.

Antibiotics, Antineoplastic↗