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Biomedical subjects

D Haraf

Publications and source records attributed to D Haraf.

16 recordsLinked to original sources
PubMed2001

Equivalent racial outcome after conformal radiotherapy for prostate cancer: a single departmental experience.

PURPOSE: African-American (AA) men with prostate cancer present with advanced disease, relative to white (W) men. This report summarizes our clinical and biochemical control (bNED) rates after conformal radiotherapy (RT). In particular, we aim to characterize any race-based outcome differences seen after comparable treatment. PATIENTS AND METHODS: We reviewed 893 patients (418 AA and 475 W) with clinically localized prostate cancer treated between 1988 and 1997. Neoadjuvant hormonal blockade was used in 22.5% of cases, and all patients received conformal RT to a median dose of 68 Gy (range, 60 to 74.8 Gy). Biochemical failure was defined according to the American Society of Therapeutic Radiology and Oncology consensus definition. Median follow-up was 24 months (range, 1 to 114 months). RESULTS: The 5-year actuarial survival, disease-free survival, and bNED rates for the entire population were 80.5%, 70.0%, and 57.6%, respectively. When classified by prognostic risk category, the 5-year actuarial bNED rates were 78.7% for favorable, 57.7% for intermediate, and 39.8% for unfavorable category patients. AA men presented at younger ages and with more advanced disease. Controlled for prognostic risk category, AA and W men had similar 5-year actuarial bNED rates in favorable (78% v 79%, P: = .91), intermediate (52% v 62%, P: =.44), and unfavorable categories (36% v 45%, P: = .09). Race was not an independent prognostic factor (P: = .36). CONCLUSION: Conformal RT is equally effective for AA and W patients. More research is needed in order to understand and correct the advanced presentations in AA men. These data suggest a need for early screening in AA populations.

Actuarial Analysis↗
PubMed2000

New scoring system identifies kidney outcome with radiation therapy in acute renal allograft rejection.

PURPOSE: To evaluate the role of radiation therapy for acute refractory renal rejection after failure of medical intervention, and to identify risk factors that influence graft survival following radiation therapy. METHODS: Between June 1989 and December 1995, 53 renal transplant recipients (34 men and 19 women) were treated with localized radiation therapy for acute renal allograft rejection. Graft rejection was defined as an increase in serum creatinine with histologic evidence of rejection on renal biopsy. Ninety-one percent were cadaveric transplant recipients. The majority of patients who experienced acute graft rejection initially received corticosteroid therapy, except for 25% who were referred for radiation therapy and steroids for the first rejection. In more recent years, patients with moderate or severe steroid-resistant or recurrent rejection received OKT3, a polyclonal antilymphocyte antibody (ATGAM), tacrolimus (FK506), or mycophenolate mofetil (MMF). Patients who failed to respond to medical treatment were then referred for radiation therapy. Ultrasound was performed for kidney localization. Treatment consisted of a dose of 600 cGy given in 3 or 4 fractions using 6 MV photons, delivered AP or AP/PA. RESULTS: The overall actuarial graft survival from the initiation of RT was 83% at 1 month, 60% at 1 year, and 36% at 5 years. The median follow-up from the date of transplant to the last follow-up was 22 months. The median time from the date of transplant to the initiation of radiotherapy was 3 months, and the median time from the initiation of radiotherapy to the last follow-up was 10 months. Variables evaluated were as follows: human leukocyte antigen matching on HLA-A, HLA-B, and HLA-DR, the transplant panel-reactive antibodies (PRA) at transplantation, number of acute rejection episodes, interval from the date of the transplant to the first rejection, serum creatinine levels at the time of the first radiation treatment, number of transplants, and concomitant immunosuppressive therapy. Independent factors examined by Cox regression modeling were: gender (p = 0.005), creatinine levels (p = 0.000), HLA-DR (p70% (p = 0.014). Each factor was scored using integral coefficients to generate four different groups. The Kaplan-Meier survival analyzed by group produces an interpretable separation of the risk factors for graft loss. CONCLUSIONS: The outcome in patients treated with radiation therapy for acute renal graft rejection can be predicted by a novel scoring system. Patients with scores of three or less are able to achieve 100% renal graft salvage, while patients who have scores of 12 or higher are not able to be salvaged with the current radiation therapy regimen. Future studies should be directed toward identifying more effective treatment for patients who have a high score based on our criteria. The scoring system should be utilized to identify patients at risk who could benefit from radiation therapy. Further study with a randomized trial utilizing this scoring system is needed to confirm the validity of the scoring system in predicting graft survival and the efficacy of radiation in patients who receive radiation therapy for acute graft rejection.

Acute Disease↗
PubMed2000

How Do head and neck cancer patients prioritize treatment outcomes before initiating treatment?

PURPOSE: To determine, pretreatment, how head and neck cancer (HNC) patients prioritize potential treatment effects in relationship to each other and to survival and to ascertain whether patients' preferences are related to demographic or disease characteristics, performance status, or quality of life (QOL). PATIENTS AND METHODS: One hundred thirty-one patients were assessed pretreatment using standardized measures of QOL (Functional Assessment of Cancer Therapy-Head and Neck) and performance (Performance Status Scale for Head and Neck Cancer). Patients were also asked to rank a series of 12 potential HNC treatment effects. RESULTS: Being cured was ranked top priority by 75% of patients; another 18% ranked it second or third. Living as long as possible and having no pain were placed in the top three by 56% and 35% of patients, respectively. Items that were ranked in the top three by 10% to 24% of patients included those related to energy, swallowing, voice, and appearance. Items related to chewing, being understood, tasting, and dry mouth were placed in the top three by less than 10% of patients. Excluding the top three rankings, there was considerable variability in ratings. Rankings were generally unrelated to patient or disease characteristics, with the exception that cure and living were of slightly lower priority and pain of higher priority to older patients compared with younger patients. CONCLUSION: The data suggest that, at least pretreatment, survival is of primary importance to patients, supporting the development of aggressive treatment strategies. In addition, results highlight individual variability and warn against making assumptions about patients' attitudes vis-à-vis potential outcomes. Whether patients' priorities will change as they experience late effects is currently under investigation.

Activities of Daily Living↗
PubMed1999

Quality of life and performance in advanced head and neck cancer patients on concomitant chemoradiotherapy: a prospective examination.

PURPOSE: To prospectively evaluate performance and quality of life (QOL) in advanced-stage head and neck cancer (HNC) patients on a curative-intent, concomitant-chemoradiotherapy (CT/XRT) (twice-daily radiation, fluorouracil, hydroxyurea, and cisplatin) regimen aimed at improving locoregional control, survival, and QOL. PATIENTS AND METHODS: Sixty-four patients were assessed before, during, and at 3-month intervals after treatment. Standardized measures of QOL (Functional Assessment of Cancer Therapy-Head and Neck), performance (Performance Status Scale for Head and Neck Cancer Patients and Karnofsky Performance Status Rating Scale), and patient-reported symptoms (McMaster University Head and Neck Radiotherapy Questionnaire) were administered. RESULTS: Acute treatment toxicities were severe, with declines in virtually all QOL and functional domains. Marked improvement was seen by 12 months; general functional and physical measures returned to baseline levels of good to excellent. Although up to a third of the patients continued to report problems with swallowing, hoarseness, and mouth pain, these difficulties were present in similar magnitudes before treatment. The following symptoms were more frequent at 12 months: dry mouth (58% v 17%), difficulties tasting (32% v 8%), and soft food diet (82% v 42%). Twelve-month diet was not related to pretreatment functioning, disease, treatment, or patient characteristics. Twelve-month QOL was best predicted by pretreatment QOL, with very little relationship to residual side effects or functional impairments. Small numbers of patients in four of the five disease sites precluded examination of outcome by site. CONCLUSION: These data support the feasibility of intense CT/XRT as primary treatment for advanced HNC. Results confirm acute toxicity but indicate that many of the treatment-related performance and QOL declines resolve by 12 months. The persistent inability to eat a full range of foods warrants further attention and monitoring.

Adolescent↗
PubMed1997

Performance and quality of life outcome in patients completing concomitant chemoradiotherapy protocols for head and neck cancer.

This study evaluated post-treatment performance and quality of life (QOL) outcome in head and neck cancer (HNC) patients treated with organ preservation, intensive chemoradiotherapy (FHX). Participants were 47 Stage II-IV HNC patients with no evidence of disease at least one year post-completion of organ preservation, concomitant FHX treatment. Patients were assessed via a semi-structured in-person interview, standardized measures of QOL (FACT-H&N, CES-D), performance (PSS-HN) and patients' perception of residual side effects. Disease, treatment and toxicity data were retrieved from medical charts and protocol records. The most salient performance impairment was inability to eat a normal solid food diet, with 50% of patients able to eat soft foods or take liquids only. This specific functional deficit was not related to global QOL, nor to specific quality of life dimensions. Dry mouth, the most frequent and severe residual effect, was not associated with outcome diet, depression or QOL. Residual pain, seen in only 15% of patients, appeared to influence both functional and QOL parameters as well as being a marker for other troublesome symptoms. Twenty-three per cent of patients were depressed; depression was associated with past problems related to alcohol abuse. Decreased QOL and increased depressive symptomatology were related to total number and severity of residual effects. The data highlight the importance of systematic study of QOL dimensions and caution against making assumptions about patients' experience of particular disease and treatment sequelae.

Activities of Daily Living↗
PubMed1996

The Performance Status Scale for Head and Neck Cancer Patients and the Functional Assessment of Cancer Therapy-Head and Neck Scale. A study of utility and validity.

BACKGROUND: The goal of this investigation was to examine the relationship between, and application of, two disease specific quality of life (QL) measures currently being employed for head and neck cancer patients: the Functional Assessment of Cancer Therapy-Head and Neck Scale (FACT-H&N) and the Performance Status Scale for Head and Neck Cancer Patients (PSS-HN). METHODS: The FACT-H&N and PSS-HN were administered to 151 head and neck cancer patients with a range of disease sites, treatment status (on vs. off treatment), and treatment modalities (surgery, radiation, and chemotherapy). RESULTS: FACT-H&N subscale and total scores and PSS-HN subscale scores proved sensitive to patients groups (showed significant and clinically meaningful differences) on the basis of treatment status (on vs. off treatment) and global performance status (Karnofsky scores). The pattern of correlations between FACT-H&N and PSS-HN subscales supported the scales' construct (convergent vs. divergent) validity. The strongest and most significant associations were observed between PSS-HN Normalcy of Diet and Eating in Public, and the head and neck subscale (HNS) of FACT-H&N, both of which were designed to measure the unique problems of head and neck cancer patients. More modest associations were observed between subscales measuring physical and functional areas of performance, social functioning, and emotional well-being. CONCLUSIONS: The FACT-HNS was found to be reliable and valid when applied to head and neck cancer patients. It clearly adds information to that collected by the parent (core) instrument. The PSS-HN also provides unique information, independent of that provided by the Karnofsky or the FACT-H&N. This study supported the multidimensional nature of QL for head and neck cancer patients, and thus the importance of assessing disease specific concerns in addition to general health status when assessing functional and QL outcome.

Adolescent↗
PubMed1995

Hydroxyurea with continuous infusion paclitaxel, 5-fluorouracil, and concomitant radiotherapy for poor-prognosis head and neck cancer.

Concomitant chemoradiotherapy holds promise in the therapy of advanced head and neck cancer. We have previously reported on the combination of 5-fluorouracil, hydroxyurea, and concomitant chemoradiotherapy administered on an alternate-week basis. In this ongoing study, we are testing the feasibility of adding continuous-infusion paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to this combination. Background information and early clinical data are presented.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

p53 mutation does not correlate with radiosensitivity in 24 head and neck cancer cell lines.

The molecular basis of tumor response to therapeutic radiation is poorly understood. Recent evidence suggests the p53 tumor suppressor gene may be involved in production of the G1 arrest seen following DNA damage by X-irradiation. It has further been proposed that tumor cells lacking the p53 checkpoint function are likely to be more sensitive to cell killing by X-irradiation because these cells enter S phase despite unrepaired DNA damage. We tested the hypothesis that tumor cells with p53 mutations are more radiosensitive by correlating the in vitro surviving fraction at 2 Gy with the mutational status of 24 head and neck squamous cell cancer cell lines. p53 mutations were present in 15 of 24 (63%) of tumors; all were homozygous changes occurring within exons 5-9. The surviving fraction at 2 Gy for the group with mutations was 0.568 compared to 0.507 for tumors without mutations (P = 0.28, Mann-Whitney test). Furthermore, no association between radiosensitivity and mutational type, codon location, or predicted amino acid alteration was noted. Our data do not support the hypothesis that p53 gene alteration predisposes tumor cells to increased cell killing via radiation.

Carcinoma, Squamous Cell↗
PubMed1993

Locoregionally advanced paranasal sinus carcinoma. Favorable survival with multimodality therapy.

To determine the efficacy of multimodality treatment for stage III and IV, advanced paranasal carcinoma, we have retrospectively reviewed local control rate and disease-free survival in patients treated at the University of Chicago (Ill). Twelve consecutive patients with stage III or IV, newly diagnosed paranasal sinus carcinoma treated between 1984 and 1991 were included in this study. Multimodality therapy was composed of a sequence of fluorouracil-cisplatin-based neoadjuvant chemotherapy (in 12 of 12 patients) followed by standard surgical resection (11 of 12 patients) and radiotherapy (12 of 12 patients, 45 to 73 Gy) with or without concomitant chemotherapy. Eleven patients (92%) are currently alive and free of disease, with a median follow-up of 55 months (range, 13 to 105 months). One patient died of persistent disease. Failure was attributed to incomplete surgical resection. There was only one major irreversible treatment complication (cisplatin ototoxic reaction). Our preliminary data suggest improved local control and survival with multimodality therapy that includes systemic neoadjuvant chemotherapy and standard tumor resection in patients with advanced paranasal sinus carcinoma. These results are superior to the reported 40% survival with bimodal therapy and are better than those achieved in our institution for other head and neck primaries with the same treatment regimens.

Adult↗
PubMed1993

Cisplatin, fluorouracil, and leucovorin augmented by interferon alfa-2b in head and neck cancer: a clinical and pharmacologic analysis.

PURPOSE: To increase the activity of cisplatin, fluorouracil (5-FU), and leucovorin (PFL) through further biochemical modulation and study the pharmacologic interaction of 5-FU and interferon alfa-2b (IFN). PATIENTS AND METHODS: Escalating doses of IFN (0.5 to 4.0 x 10(6) U/m2/d x 6) were added to cisplatin 100 mg/m2, continuous infusion 5-FU 800 or 640 mg/m2/d x 5, and leucovorin 100 mg orally every 4 hours. Forty-eight previously untreated patients with locoregionally advanced head and neck cancer received up to three cycles of PFL-IFN. RESULTS: Twenty-one patients were treated during a phase I cohort study. Dose-limiting mucositis was seen with 800 mg/m2/d of 5-FU and 0.5 x 10(6) U/m2/d of IFN. After decreasing the 5-FU dose to 640 mg/m2/d, the maximally tolerated dose (MTD) of IFN was 2.0 x 10(6) U/m2/d. Mucositis and myelosuppression were dose-limiting. Of 34 patients treated at this MTD, 56% (95% confidence interval, 39% to 73%) had a complete remission. There was no correlation between 5-FU clearance and IFN dose. Pharmacodynamic analyses at the MTD showed that older age, female sex, and higher 5-FU area under the time versus concentration curve (AUC) were associated with lower nadir counts and/or increased mucositis. Seven patients with diabetes mellitus had significantly increased myelosuppression, serum creatinine, hypocalcemia, higher 5-FU concentrations, and lower 5-FU clearance compared with nondiabetics. CONCLUSION: The recommended doses for PFL-IFN are 640 mg/m2/d for 5-FU and 2.0 x 10(6) U/m2/d for IFN. Sex, age, 5-FU AUC, and diabetes mellitus may have an impact on the pharmacodynamics of this regimen.

Adolescent↗
PubMed1992

Occurrence of p53 gene deletions and human papilloma virus infection in human head and neck cancer.

Little is known regarding the molecular genetic events in head and neck carcinoma. Epidemiological evidence suggests that both alcohol and tobacco use are related to the development of these neoplasms, and viral infections have also been postulated to play a role in some tumors. Loss of p53 tumor suppressor gene function has been found in many malignancies and can occur through either gene mutation or by interaction with the E6 protein of oncogenic human papilloma viruses (HPV). Because the mucosal surfaces of the head and neck are exposed to mutagens and HPVs, we studied DNA derived from 30 stage I-IV squamous cell carcinomas of the head and neck (9 primary tumors and 21 early passage cell lines) for p53 gene mutations as well as for the presence of oncogenic HPV DNA. Exons 2 through 11 of the p53 gene were examined using single strand conformation polymorphism analysis followed by direct genomic sequencing of all variants. HPV detection was done using polymerase chain reaction amplification with HPV E6 region type specific primers as well as L1 region degenerate ("consensus") primers; HPV type was determined by restriction fragment length polymorphism analysis of the amplified fragment as well as by Southern blotting of genomic DNA. Sixteen of 30 tumors (53%) had p53 mutations and oncogenic HPV DNA was detected in 3 of 30 (10%) tumors, none of which had p53 mutations. The p53 mutational spectrum observed was characterized by equal frequencies of transversions (6 of 16), transitions (5 of 16), and deletions (5 of 16). This distribution of mutations differs from the spectrum of p53 mutation reported in esophageal (P = 0.05) and lung (P = 0.02) cancers, two other tobacco associated neoplasms. A previously undescribed clustering of 3 mutations at codon 205 was also observed. A trend toward a shorter time to tumor recurrence after treatment was noted for those patients with tumors exhibiting p53 gene mutations, and no relationship between p53 mutations and tumor stage or node status was noted. Alteration in p53 gene function appears common in head and neck cancer, and the mutational spectrum observed may reflect the role of different mutagens or mutagenic processes than those responsible for the p53 mutations in lung and esophageal neoplasms.

Alcohol Drinking↗
PubMed1991

Temporal bone chemodectomas--comparing surgery and radiation therapy.

We reviewed the literature concerning curative treatment for chemodectomas of the temporal bone. Local control and complication rates were calculated from the published series for three therapeutic approaches: Surgery alone, radiation before or after surgery, and radiation alone. The local control rates were similar, 86%, 90%, and 93% respectively. Patients suffered a high rate of treatment-related morbidity following surgical excision of glomus jugulare lesions. Serious sequelae from radiation therapy were rare. We feel radiation therapy should be considered as primary treatment for glomus jugulare tumors.

Humans↗
PubMed1990

Modeling of dose to tumor and normal tissue from intraperitoneal radioimmunotherapy with alpha and beta emitters.

Dose distributions for normal and tumor tissues from intraperitoneally administered radiolabeled antibodies have been calculated for 90-Yttrium (90Y), 131-Iodine (131I), and 211-Astatine (211At). The dose calculations use data on the activity of intraperitoneal fluid administered, the percent injected dose/gm uptake by tumor, biological half life, and a model for diffusion of antibody/radionuclide complex into peritoneal tissues. Calculations are performed for planar and hemispherical tumor shapes, ranging in size to establish the influence of geometry on dose distribution. Calculations for tumor geometry obtained from biopsies are also performed. When the activity is concentrated on or near the tumor surface, the maximum dose to a planar tumor for a 20 mci administration of 90Y is approximately 60 Gy, and falls rapidly to 50% of this value within 1 mm. However, for a hemispherical tumor, the dose is a maximum of 26 Gy, with an average of approximately 20 Gy. The surface dose from 131I (130 mci) is 240 Gy, and diminishes to 20 Gy in .05 cm in the planar case, whereas a hemispherical tumor receives a dose of 90 Gy over a large fraction of the volume, with the distal portions receiving 40 Gy. The surface dose for an administration of 70 mci of 211 At is 450 Gy and decreases to 50% of this value in 30 microns. Both surface geometry and tumor size are important determinants in the heterogeneity of tumor dose, as are the dose administered, antibody uptake, biodistribution, and residence time factors. These initial studies suggest that the size of disease which may be effectively treated is much less than the range of the particle emitted by radiolabeled antibodies. Furthermore, therapy is ultimately limited by the degree to which the antibody/radionuclide complex can diffuse and permeate the tumor.

Antibodies, Monoclonal↗
PubMed1990

Radioresistant derivatives of an X-ray-sensitive CHO cell line exhibit distinct patterns of sensitivity to DNA-damaging agents.

X-ray-resistant clones of the xrs-5 radiosensitive derivative of the CHO-K1 cell line were generated by transfecting cosmid library DNAs into the X-ray-sensitive cells. Transfectants were selected for both a dominant drug resistance marker present in the vector sequences and return to wild-type survival. Three cell lines were isolated which show X-ray survival characteristics similar to parental K1 cells. These revertant lines were examined for their cross-sensitivity to cis-diamminedichloroplatinum(II) (cisplatin) and bleomycin. Although these cell lines reverted with regard to X-ray sensitivity, they retained their sensitivity to cisplatin. Furthermore, changes in bleomycin and X-ray sensitivity did not correlate. There was a positive correlation between return to wild-type radiosensitivity and an increase in the rate of DNA double-strand break rejoining.

Animals↗
PubMed1988

In vitro radiobiological parameters of human sarcoma cell lines.

In vitro radiobiologic survival parameters have been determined for 7 human osteosarcoma, 5 human soft tissue and bone sarcomas, and 4 Ewing's sarcoma cell lines. The mean D0 values were 99.5 +/- 11.6 cGy, 90.5 +/- 7.7 cGy and 95.8 +/- 7.9 cGy for osteosarcomas, soft tissue and bone sarcomas and Ewing's sarcomas, respectively. These in vitro survival data do not predict the clinical radiation resistance generally attributed to osteosarcomas and soft tissue and bone sarcomas, and do not differ substantially from the results obtained with the clinically radioresponsive Ewing's sarcomas.

Bone Neoplasms↗