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D J Haraf

Publications and source records attributed to D J Haraf.

At least 37 records · Page 2Linked to original sources
PubMed1998

Phase I study of docetaxel with concomitant thoracic radiation therapy.

PURPOSE: The taxanes have demonstrated activity as radiation sensitizers in preclinical studies. This study was designed to determine the maximum-tolerated dose (MTD), optimal schedule, and toxicities of docetaxel in combination with concomitant standard chest radiotherapy. PATIENTS AND METHODS: Twenty-nine patients with advanced non-small-cell lung or esophageal cancer enrolled in this phase I study to evaluate escalating docetaxel doses at three schedules. Docetaxel was administered as two 21-day cycles at doses of 40, 60, and 75 mg/m2 per cycle. Docetaxel administration schedules were as follows: schedule A, once every 3 weeks; schedule B, 2 of 3 weeks; or schedule C, weekly. Six weeks of concomitant standard chest radiotherapy in 1.8- to 2.0-Gy daily fractions was delivered to 60 Gy total. RESULTS: Dose-limiting esophagitis and neutropenia were encountered with schedules A and B at docetaxel doses of 60 mg/m2 per cycle. The docetaxel MTD for schedules A and B was 40 mg/m2 per cycle. Dose-limiting esophagitis was also observed with schedule C; however, there was no neutropenia. For schedule C, we identified the MTD as 60 mg/m2 per cycle (20 mg/m2/wk). Other toxicities encountered included thrombocytopenia, hypersensitivity reaction, and pulmonary infiltrates (fatal in two patients). Late toxicity of esophageal stricture occurred in five patients. CONCLUSION: Esophagitis and neutropenia are the dose-limiting toxicities of docetaxel administered with concomitant chest radiotherapy. Weekly administration of docetaxel allows for the highest total docetaxel dose during chest radiotherapy. We identified the recommended phase II docetaxel dose as 20 mg/m2 administered weekly with concomitant chest radiotherapy for 6 weeks.

Adult↗
PubMed1998

Phase I study of concomitant chemoradiotherapy with paclitaxel, fluorouracil, and hydroxyurea with granulocyte colony-stimulating factor support for patients with poor-prognosis cancer of the head and neck.

PURPOSE: We have previously demonstrated high locoregional control rates in patients with poor-prognosis head and neck cancer using fluorouracil (5-FU), hydroxyurea (HU), and concomitant radiotherapy (RT) (FHX). In the trial reported here, we added paclitaxel to the FHX base and used hyperfractionated RT to determine the maximum-tolerated dose (MTD), toxicities, and response rate in a poor-prognosis group of patients. METHODS: Fifty-five patients who had either failed to respond to prior RT (n = 25) or surgery, had a coexistent or prior second malignancy, or who had unresectable or metastatic disease and an expected 2-year survival rate less than 10%, were treated. Chemoradiotherapy consisted of 2 Gy on days 2 to 6 (once-daily RT cohorts) or 1.5 Gy twice a day (hyperfractionated cohorts). Simultaneous HU (500 or 1,000 mg twice per day for 11 doses) and infusional 5-FU (600-800 mg/m2/d for 5 days) were given along with infusional paclitaxel at escalating doses of 5 to 25 mg/m2/d for 5 days. Granulocyte colony-stimulating factor (G-CSF) was administered on days 7 through 13 at 5 microg/kg/d. Cycles were repeated every 14 days until completion of RT. Plasma paclitaxel levels were determined on day 4 of cycle 1. RESULTS: Dose-limiting toxicities (DLTs) consisted of myelosuppression, mucositis, dermatitis, and diarrhea. Plasma concentrations of paclitaxel greater than 10 nmol/L were achieved in 65% of patients at the recommended phase II dose (RPTD) level of paclitaxel. Seventy percent of assessable patients achieved a complete response (CR) to therapy. Twenty patients were treated at the RPTD of HU 500 mg orally twice daily for 11 doses, 5-FU 600 mg/m2/d by continuous infusion for 5 days; and paclitaxel 20 mg/m2/d by continuous infusion for 5 days, with twice-daily RT. CONCLUSION: The addition of infusional paclitaxel and hyperfractionated RT to FHX is feasible. Radiosensitizing levels of paclitaxel are achieved in most patients. The high locoregional control rate of this regimen justifies further investigation in previously untreated patients.

Adult↗
PubMed1998

Phase I study of vinorelbine, cisplatin, and concomitant thoracic radiation in the treatment of advanced chest malignancies.

PURPOSE: The cisplatin-vinorelbine regimen has superior activity in advanced non-small-cell lung cancer (NSCLC). We conducted a phase I trial to identify the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of this regimen with concomitant thoracic radiation (RT) in patients with advanced chest malignancies. PATIENTS AND METHODS: Patients with advanced chest malignancies that required RT were enrolled onto this phase I study of standard chest radiation (30 daily 2-Gy fractions for a total of 60 Gy) and concurrent chemotherapy with cisplatin starting at 100 mg/m2 every 3 weeks and vinorelbine starting at 20 mg/m2/wk. RESULTS: Thirty-seven patients were treated on this study. Two of three patients treated at the maximum-administered dose of cisplatin 100 mg/m2 per cycle and vinorelbine 25 mg/m2/wk experienced acute DLT (neutropenia), which required deescalation. The dose level of cisplatin 100 mg/m2 and vinorelbine 20 mg/m2/wk, although tolerated acutely, produced delayed esophagitis, which proved dose-limiting. The recommended phase II dose was cisplatin 80 mg/m2 every 3 weeks and vinorelbine 15 mg/m2 given 2 of every 3 weeks with concomitant chest RT. CONCLUSION: Concomitant chemoradiotherapy with cisplatin and vinorelbine is feasible. The recommended phase II dose is cisplatin 80 mg/m2 every 3 weeks with vinorelbine 15 mg/m2 given twice over 3 weeks on a day 1/day 8 schedule. Esophagitis is the DLT, with neutropenia occurring at higher dose levels. A Cancer and Leukemia Group B (CALGB) phase II trial is currently underway to evaluate further the efficacy and toxicities of this regimen in unresectable stage III NSCLC.

Adult↗
PubMed1998

Induction chemotherapy followed by concurrent chemoradiation for advanced head and neck cancer: improved disease control and survival.

PURPOSE: To determine tumor response rate, patterns of failure, toxicity, and survival in advanced squamous head and neck cancer after a combined treatment program that consists of induction chemotherapy, organ-sparing surgery, and concurrent chemoradiation. Long-term outcome data are presented. PATIENTS AND METHODS: Between July 1991 and March 1993, 93 patients received three cycles of induction chemotherapy that consisted of cisplatin, fluorouracil (5-FU), l-leucovorin, and alpha-interferon2b (PFLl-alpha) followed by optional limited surgery and six to eight cycles of 5-FU, hydroxyurea, and concurrent radiation (FHX) to a total radiation dose of 65 to 75 Gy. RESULTS: Ninety-three patients were entered onto this study and 97% had stage IV disease, with 66 patients who were N2 or N3. Sixty-one patients (66%) achieved a clinical complete remission (CR) after induction therapy. Thirty-four patients underwent surgery. Seventy-nine patients proceeded to FHX. With a median follow-up time of 43 months for surviving patients, 20 patients have had disease progression (13 local, two distant, five both), and there have been 35 deaths (18 from disease, six treatment-related, two from a second primary, and nine for other medical reasons). At 5 years, progression-free survival is 68%, and overall survival is 62%. Surgery was organ-preserving, as only a single laryngectomy and no glossectomies were performed in primary management. Acute toxicity related to PFLl-alpha consisted of severe or life-threatening mucositis in 57% and leucopenia in 65% of patients. During FHX, 81% of patients had grade 3 or 4 mucositis. CONCLUSION: PFLl-alpha is a highly active regimen that induced clinical CR in two thirds of patients. When followed by limited surgery and FHX, resultant local and distant disease control, organ preservation, and overall 5-year survival are very promising in high-risk stage IV patients. Based on these local control and survival data, further evaluation of this treatment sequence, induction chemotherapy followed by concurrent chemoradiation, is warranted. Identification of similarly active but less toxic regimens is a high priority.

Adolescent↗
PubMed1998

Combined modality therapy in non-small cell lung and esophageal cancer: a phase I dose-escalation study of docetaxel with concurrent radiotherapy.

The effective treatment of non-small cell lung cancer requires both locoregional and systemic therapy. Outcome in intermediate-stage malignancies of the chest may be improved by combining chemotherapy and radiotherapy. Several combined-modality trials involving the platinum compounds, vinorelbine, gemcitabine, and the taxanes have been recently conducted. In one such phase I dose-escalation study of 29 patients with non-small cell lung cancer or esophageal cancer, the concurrent administration of docetaxel and radiotherapy at a dose of 2 Gy/d for 6 weeks was shown to be feasible. Objective tumor responses were observed, and further studies of docetaxel in combination with radiotherapy are indicated.

Adult↗
PubMed1998

Oral 5-FU alternatives for the treatment of head and neck cancer.

The common clinical presentations of head and neck cancer include early (stage I or II) disease, locally or regionally advanced (stage III or IV, M0) disease, and recurrent or metastatic disease (< 5% of patients). Patients with stage I-II disease are usually cured following surgery or radiotherapy; those with more advanced disease, however, will benefit from chemotherapy--either as induction treatment to avoid surgery and preserve the larynx, or as simultaneous chemoradiotherapy for patients with locoregionally advanced disease; patients presenting with metastatic disease and those with recurrent disease receive chemotherapy as the primary treatment modality. The clinical experience with oral chemotherapy in head and neck cancer patients is limited, partly because of the anatomic location of the disease and complications of local treatment. At the University of Chicago, several regimens that include oral chemotherapy have been studied, including infusional 5-fluorouracil/oral hydroxyurea/radiotherapy, and eniluracil/oral 5-FU/radiotherapy. These trials and others assessing oral agents in the treatment of patients with head and neck cancer will be discussed.

Administration, Oral↗
PubMed1997

Continuous infusion paclitaxel, 5-fluorouracil, and hydroxyurea with concomitant radiotherapy in patients with advanced or recurrent head and neck cancer.

Concomitant chemotherapy and radiation in the treatment of patients with advanced head and neck cancer is under intense investigation, although the optimal regimen remains undefined. The head and neck cancer program at the University of Chicago has reported encouraging results with concomitant 5-fluorouracil, hydroxyurea, and radiation administered every other week to patients with locally advanced or recurrent disease. The feasibility of adding continuous-infusion paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to this combination currently is being tested in a phase I trial. We present here the rationale and preliminary results of this regimen.

Aged↗
PubMed1997

Clinical studies of docetaxel (Taxotere) and concomitant chest therapy.

The administration of concomitant chemoradiotherapy has been shown to increase local and regional control of non-small cell lung cancer. Docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) has single-agent activity in non-small cell lung cancer, as well as radiation-enhancing potential in preclinical studies. Therefore, its investigation with concomitant radiotherapy in the clinical setting is justified. Since the clinical interactions of docetaxel and concomitant chest radiotherapy have not been previously described, we initiated a phase I study with the goal of determining the maximum tolerated dose of docetaxel and the optimal schedule for its administration during a standard course of radiation therapy to the chest, in addition to defining the dose-limiting toxicities of this regimen. This report describes the design and preliminary results of this study.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Volumetric visualization of anatomy for treatment planning.

PURPOSE: Delineation of volumes of interest for three-dimensional (3D) treatment planning is usually performed by contouring on two-dimensional sections. We explore the usage of segmentation-free volumetric rendering of the three-dimensional image data set for tumor and normal tissue visualization. METHODS AND MATERIALS: Standard treatment planning computed tomography (CT) studies, with typically 5 to 10 mm slice thickness, and spiral CT studies with 3 mm slice thickness were used. The data were visualized using locally developed volume-rendering software. Similar to the method of Drebin et al., CT voxels are automatically assigned an opacity and other visual properties (e.g., color) based on a probabilistic classification into tissue types. Using volumetric compositing, a projection into the opacity-weighted volume is produced. Depth cueing, perspective, and gradient-based shading are incorporated to achieve realistic images. Unlike surface-rendered displays, no hand segmentation is required to produce detailed renditions of skin, muscle, or bony anatomy. By suitable manipulation of the opacity map, tissue classes can be made transparent, revealing muscle, vessels, or bone, for example. Manually supervised tissue masking allows irrelevant tissues overlying tumors or other structures of interest to be removed. RESULTS: Very high-quality renditions are produced in from 5 s to 1 min on midrange computer workstations. In the pelvis, an anteroposterior (AP) volume rendered view from a typical planning CT scan clearly shows the skin and bony anatomy. A muscle opacity map permits clear visualization of the superficial thigh muscles, femoral veins, and arteries. Lymph nodes are seen in the femoral triangle. When overlying muscle and bone are cut away, the prostate, seminal vessels, bladder, and rectum are seen in 3D perspective. Similar results are obtained for thorax and for head and neck scans. CONCLUSION: Volumetric visualization of anatomy is useful in treatment planning, because 3D views can be generated without the need for segmentation. When relationships among anatomical structures, rather than geometric models of them, are important, volume rendering presents advantages. The presented algorithm is readily adaptable to distributed parallel implementation on a network of heterogeneous workstations.

Anatomy, Cross-Sectional↗
PubMed1996

Electron-photon field matching in the treatment of paranasal sinus tumors: a case report.

The treatment planning of paranasal sinus tumors is technically demanding due to the compact anatomy of the region and the close proximity of critical structures. In the majority of cases, conventional approaches utilizing 2 or 3 photon fields are adequate. However, in patients with locally advanced disease, these standard techniques may result in the unnecessary treatment of surrounding structures. We present here a case in which, because of the complex tumor geometry, conventional techniques would result in treating through both orbits. A novel treatment approach has been devised in which opposed lateral photon fields are matched to an anterior electron field (both in depth and in profile) to provide a uniform dose distribution to the target volume, while minimizing the dose to certain critical structures. The treatment design, in particular the methodology of electron-photon field matching as well as the specification of tissue compensation and customized blocking, is discussed.

Aged↗
PubMed1996

Treatment of prostate cancer using external beam radiotherapy after laparoscopic pelvic lymph node dissection.

OBJECTIVES: To evaluate the results of prostatic irradiation in men with clinically localized prostate cancer and no laparoscopic evidence of nodal metastases compared with a cohort of patients who received radiation therapy with no prior surgical staging. PATIENTS AND METHODS: Thirty-one men with clinically localized prostate cancer and no evidence of pelvic nodal metastases after laparoscopic pelvic lymph node dissection received external beam radiation therapy to the prostate (65-70 Gy). The mean and median prostate specific antigen (PSA) levels in these men before treatment were 41.6 ng/mL and 28.0 ng/mL, respectively, and the mean Gleason sum was 6.1 (range 3-7). During the same interval, a group of 42 consecutive men with clinically localized prostate cancer were treated by external beam radiation therapy with no laparoscopic staging of the pelvic nodes. Treatment failure was defined by the development of bone metastases or a rising PSA level at least 6 months after the completion of radiotherapy. RESULTS: Radiation therapy was generally well tolerated after laparoscopy and no patient required hospitalization or surgery for side-effects related to the treatment. The median duration of follow-up in the 31 men who underwent laparoscopy was 21.5 months. The probability of treatment failure in this group was 41.8% and 56.3% with 24 and 30 months follow-up, respectively. When controlling for pre-treatment PSA level, grade and stage, there was no significant difference in the treatment failure rate between the groups treated with and without laparoscopic staging. CONCLUSIONS: These results suggest that there is no difference in treatment outcome with laparoscopic pelvic lymphadenectomy before external beam radiation therapy in high-risk patients who have significant pre-treatment elevations of PSA level.

Aged↗
PubMed1996

Re-irradiation with concomitant chemotherapy of unresectable recurrent head and neck cancer: a potentially curable disease.

PURPOSE: The purpose of this study was to review the outcome following concomitant chemoradiation therapy in previously irradiated patients with locally or regionally recurrent or persistent head and neck cancer considered unresectable for cure. METHODS AND MATERIALS: We identified 45 patients treated between 1986 and 1993 with unresectable locally or regionally recurrent disease who were treated on one of four concomitant chemoradiotherapy phase I/II studies at the University of Chicago. All patients received hydroxyurea (HU), 5-fluorouracil (5-FU) and concomitant radiation therapy on an alternate week schedule (FHX). Cisplatin was added to FHX in three of the studies. RESULTS: The overall survival, progression-free survival, and local/regional control at 5 years was 14.6%, 13.5% and 20%, respectively, in a cohort of patients whose disease is almost universally fatal. Fatal treatment related complications were observed in 5 (11%) of patients. Two of these complications were related to radiation therapy. Stepwise Cox regression analysis revealed that dose and protocol were significantly correlated with survival, progression-free survival and local/regional control. A direct correlation was observed with radiation dose and an inverse correlation was observed with the initial FHX dose escalation study. The 2-year survival was 35% in patients receiving over 58 Gy compared to 8% for those receiving less than 58 Gy. CONCLUSIONS: Our results show that aggressive re-irradiation with concomitant chemotherapy of recurrent head and neck cancer results in the cure of some patients with acceptable toxicity if tumoricidal doses are applied. These results are in contrast to historical series of chemotherapy alone which results in limited palliation of brief duration and almost no chance of cure. Thus, re-irradiation with concomitant chemotherapy should be further investigated as an alternative to chemotherapy alone in multi-center or cooperative group randomized trials.

Adult↗
PubMed1996

Pharmacodynamics of fluorouracil-based induction chemotherapy in advanced head and neck cancer.

PURPOSE AND METHODS: To optimize the biochemical modulation of fluorouracil (5-FU), we administered the pure I-stereoisomer of leucovorin (LV) as a 132-hour continuous intravenous infusion (CIV) with cisplatin 100 mg/m2, 5-FU 640 mg/m2/d as a 120-hour CIV, and interferon alfa-2b (IFN) at 2 MU/m2/d for 6 days for three cycles (I-PFL-IFN). Pharmacologic parameters included morning (AM) and afternoon (PM) plasma concentrations of 5-FU, LV and its active metabolite 5-methyl tetrahydrofolate (MTHF), and dihydropyrimidine dehydrogenase (DPD) activity in peripheral mononuclear cells. RESULTS: Eighty-nine patients were treated (86 stage IV). Neutropenia and mucositis were the most common toxicities. Sixty-six percent achieved a complete remission (CR). There was a trend for higher PM versus AM 5-FU concentrations (median, 1.64 v 1.51 mumoles/L; P = .08), but not for LV plus MTHF (P = .66). The mean +/- SD DPD activity was 0.21 +/- 0.14 nmol/min/mg and did not correlate with plasma concentrations of 5-FU or LV plus MTHF or clinical toxicities. Higher PM 5-FU concentrations correlated with worse leukopenia (P = .04) and severity of mucositis (P = .04). PM 5-FU concentration was higher in women than in men (P = .07), with no apparent difference in severity of toxicities. The maximum 5-FU concentration was higher in CR than non-CR patients (median, 2.01 v 1.54 mumoles/L; P = .02) and higher in women than men who achieved a CR (median, 2.77 v 1.91 mumoles/L; P = .03). No correlation of CR with dose-intensity was found. CONCLUSION: L-PFL-IFN is active in stage IV head and neck cancer. 5-FU concentration is a significant predictor of toxicity. In women, optimization of response outcome requires a higher 5-FU concentration. Individualized 5-FU dosing to obtain higher 5-FU plasma concentrations may be indicated.

Adolescent↗
PubMed1996

Vinorelbine (Navelbine), cisplatin, and concomitant radiation therapy for advanced malignancies of the chest: a Phase I study.

Most patients with advanced solid tumors of the chest will have local and/or distant disease progression despite standard therapy. Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) is a new semisynthetic vinca alkaloid with single-agent activity in lung cancer that recently also has been shown to act as a radiosensitizer in vitro. This study aims to define the maximum tolerated dose and dose-limiting toxicity when vinorelbine is given with cisplatin and concomitant radiation therapy. To date, 25 patients with advanced malignancies of the chest have been treated in a dose-escalation trial of vinorelbine administered once weekly with cisplatin (100 mg/m2 every 21 days) and concomitant thoracic radiation therapy (2 Gy/d x 30 fractions for 60 Gy). Vinorelbine was initially given at 20 and 25 mg/m2/wk. Acute dose-limiting toxicity was myelosuppression, which was seen at a vinorelbine dose of 25/mg/m2/wk, with grade 4 neutropenia in two of three patients and one treatment-related death from neutropenic sepsis. At vinorelbine 20/mg/m2/wk, no acute dose-limiting toxicity was seen, but grade 3 or 4 esophagitis developed in three of six patients near the end or after completion of radiation therapy. We subsequently decreased the administration of vinorelbine to weeks 1, 2, 4, and 5. Tolerance appears to be greater with this schedule; however, severe or life-threatening esophagitis at the completion of therapy continues to be observed. Given these preliminary results, it appears feasible to treat patients with advanced chest malignancies with concomitant cisplatin, vinorelbine, and radiation therapy. The significant dose reduction of vinorelbine that is necessary with concomitant radiation therapy provides the first in vivo evidence of a strong radiosensitizing effect of vinorelbine. The schedule is currently being modified to reduce the incidence of esophagitis.

Adult↗
PubMed1996

Human papilloma virus and p53 in head and neck cancer: clinical correlates and survival.

Recent studies have shown that p53 mutations are frequently found in cancer of the head and neck, whereas others have indicated that human papilloma virus (HPV) infection may be involved. Thus far, no studies have examined both p53 and HPV in the same patient population and correlated the results with clinical characteristics and outcome. The purpose of this study was to examine any interrelationship between p53 and HPV in patients with squamous cell carcinoma (SCC) of the head and neck. We also planned to correlate the experimental findings with clinical characteristics, known risk factors, and treatment outcome to determine whether any prognostic factors could be detected. Archival material from 66 patients with SCC of the head and neck were selected for study based on the availability of tissue from the primary tumors prior to treatment. A data base was constructed containing all clinical parameters at the time of diagnosis and risk factors. Genomic DNA was isolated and amplified using PCR, followed by SSCP analysis and direct genomic sequencing of all variants to detect p53 mutations. Two independent methods were used for HPV detection: (a) PCR amplification using primers homologous to the E6 region of HPV 16, 18, and 33, followed by RFLP analysis; and (b) PCR amplification with HPV L1 consensus primers, followed by triple restriction enzyme digestion. The results were entered into the data base for statistical analysis. Twenty-four percent of patients were found to have p53 mutations, and 18% were positive for HPV infection. Only one patient was positive for both. Tonsilar cancer was strongly correlated with HPV (P = 0.0001) and inversely correlated with p53 (P = 0.03). The only clinical parameter associated with p53 mutation was a trend toward a heavier smoking history. A subset analysis of the patients with tonsilar cancer revealed inverse correlations with smoking (P = 0. 015) and alcohol use (P = 0.05). Also, white patients with SCC of the tonsil were more likely to be HPV positive (P = 0.015). No significant relationships with outcome were detected with either p53 or HPV in the entire population. A subset analysis of patients with stage IV disease revealed that HPV infection was correlated with overall survival. This is the largest study to date to examine both p53 and HPV in patients with SCC of the head and neck. Our results suggest that HPV may be involved in the development of these cancers in patients without traditional risk factors and that HPV-related cancers are more prevalent in the white race.

Adult↗
PubMed1995

A method of analyzing rectal surface area irradiated and rectal complications in prostate conformal radiotherapy.

PURPOSE: To develop a method of analyzing rectal surface area irradiated and rectal complications in prostate conformal radiotherapy. METHODS AND MATERIALS: Dose-surface histograms of the rectum, which state the rectal surface area irradiated to any given dose, were calculated for a group of 27 patients treated with a four-field box technique to a total (tumor minimum) dose ranging from 68 to 70 Gy. Occurrences of rectal toxicities as defined by the Radiation Therapy Oncology Group (RTOG) were recorded and examined in terms of dose and rectal surface area irradiated. For a specified end point of rectal complication, the complication probability was analyzed as a function of dose irradiated to a fixed rectal area, and as a function of area receiving a fixed dose. Lyman's model of normal tissue complication probability (NTCP) was used to fit the data. RESULTS: The observed occurrences of rectal complications appear to depend on the rectal surface area irradiated to a given dose level. The patient distribution of each toxicity grade exhibits a maximum as a function of percentage surface area irradiated, and the maximum moves to higher values of percentage surface area as the toxicity grade increases. The dependence of the NTCP for the specified end point on dose and percentage surface area irradiated was fitted to Lyman's NTCP model with a set of parameters. The curvature of the NTCP as a function of the surface area suggests that the rectum is a parallel structured organ. CONCLUSIONS: The described method of analyzing rectal surface area irradiated yields interesting insight into understanding rectal complications in prostate conformal radiotherapy. Application of the method to a larger patient data set has the potential to facilitate the construction of a full dose-surface-complication relationship, which would be most useful in guiding clinical practice.

Dose-Response Relationship, Radiation↗
PubMed1995

Photon neutron mixed-beam radiotherapy of locally advanced prostate cancer.

PURPOSE: In this article we present the results of mixed-beam, photon/neutron radiation therapy in 45 patients with locally advanced, bulky, or postoperative recurrent prostate cancer treated at the University of Chicago between 1978 and 1991. Survival, disease-free survival, local control, and long-term complications are analyzed in detail. METHODS AND MATERIALS: Between 1978 and 1991, 45 patients with locally advanced (> 5 cm State B2, Stage C, or Stage D1) prostate cancer underwent mixed-beam (photon/neutron) radiation therapy. Forty percent of the treatment was delivered with neutron irradiation at either the University of Chicago or Fermilab. Sixty percent of treatment was delivered with photons at the University of Chicago. Initially, the whole pelvis was irradiated to 50 photon Gy equivalent. This was followed by a boost to the prostate for an additional 20 photon Gy equivalent. RESULTS: The median follow-up for patients in this series is 72 months. The overall 5-year actuarial survival was 72%, and the 5-year disease-free survival was 45%. Thus far, 18 patients have died. Eleven patients have died from prostate cancer and 7 from other medical illness. Twenty-seven patients are alive, and 12 of these patients have recurrent and or metastatic disease. The local control rate was 89% (40 out of 45). Histologic material was available on 18 patients following treatment (i.e., prostate biopsy in 16 patients and autopsy in 2 patients) and was negative for carcinoma in 13 (72%). Significant Grade 3-5 complications occurred in 36% (16 out of 45) of the patients treated with mixed-beam radiation therapy and were related to dose and beam quality. Factors related to survival, disease-free survival, local control, and complications are analyzed. CONCLUSIONS: The survival and local control results of mixed-beam radiation therapy at the University of Chicago appear to be superior to those series using photon radiation in patients with locally advanced prostate carcinoma. Mixed-beam radiation therapy should remain an alternative to studies using dose escalation or implant techniques as a method to increase local control and survival at institutions with this capability. However, appropriate plans with high-energy neutrons are necessary to minimize complications.

Actuarial Analysis↗