Asymmetric allylboration and ring closing alkene metathesis: a novel strategy for the synthesis of glycosphingolipids.

A novel strategy for the synthesis of D,L-glucosylceramide 1, a member of the glycosphingolipid class of natural products is described. Reagent-controlled asymmetric Brown allylboration gave excellent stereochemical control in the construction of adjacent stereocenters in the sphingoid base portion of the molecule. The trans-configured double bond was obtained as a single geometrical isomer by use of silicon-tethered olefin metathesis employing the Schrock carbene [(CF3)2MeCO]2Mo(=CHCMe2Ph)(=NC6H3-2,6-i-Pr2++ +) and in situ PhLi-induced ring-opening of the intermediate 5,6-dihydro-2H-1,2-oxasiline followed by protodesilylation with TBAF in DMSO. The synthesis was completed by long chain amide formation and global deprotection.

Does race influence survival for esophageal cancer patients treated on the radiation and chemotherapy arm of RTOG #85-01?

PURPOSE: In reported retrospective non-randomized trials of treatment of esophageal carcinoma, blacks have a lower survival from esophageal cancer than whites. None of these studies has accounted for the extent of disease, or the methods and quality of treatment. We reviewed the data that included only patients treated on the chemoradiation arm of the RTOG-8501 esophageal carcinoma trial to see if there were differences in overall survival between black and white patients receiving the same standard of care. METHODS AND MATERIALS: One hundred-nineteen patients, 37 blacks and 82 whites were evaluated who met the criteria for receiving chemoradiation of 5000 cGy and four courses of Cisplatin (75 mg/m2) and Fluorouracil (1000 mg/m2 for 4 days). RESULTS: Blacks had squamous histology only, with 86% of blacks having weight loss of 10 lbs. or more compared to 56% of whites (p = 0.001). In addition, blacks had larger tumors and more difficulty eating (p = 0.010). Overall, there was no difference in the Kaplan-Meier median survival estimate by race (p = 0.2757). Only when we limited the analysis to the "squamous histology" subgroup, stratified according to age >70 vs. <70 years (p = 0.0002), and nodal status (p = 0.0177) in a Cox regression model analysis, did race appear to be a significant factor (p = 0.0012). However, using the entire database, the age effect was found to be a "bimodal" effect, wherein the "youngest" (< age 60 years) and "oldest" patients (age > 70 years) did poorly. Because of the dramatic differences in the age and histology distributions between blacks and whites, this issue could not be resolved in the subset of squamous only who received chemoradiation. CONCLUSIONS: The increasing incidence of adenocarcinoma among white patients without a corresponding increase of this histology in blacks reflects a difference in diet and or lifestyle compared to blacks that deserves additional study. When treated aggressively with chemoradiation, race did not appear to be a statistically significant factor for overall survival.

Concomitant chemotherapy and reirradiation as management for recurrent cancer of the head and neck.

Thirty-five patients with inoperable recurrent head and neck cancer previously treated with definitive irradiation were treated with reirradiation and concomitant chemotherapy. Patient records were retrospectively reviewed to assess toxicity, response, and survival. Patients received one of three regimens: 1) 40 Gy total (2 Gy daily), 300 mg/m2 5-fluorouracil intravenous bolus, and 2 g hydroxyurea orally daily for 5 days; 2) 48 Gy total (1.2 Gy twice daily), 300 mg/m2 5-fluorouracil intravenous bolus, and 1.5 g hydroxyurea orally daily for 5 days; 3) 60 Gy total (1.5 Gy twice daily), 300 mg/m2 5-fluorouracil intravenous bolus, and 1.5 g hydroxyurea orally daily for 5 days. For all regimens, treatment was given only on weeks 1, 3, 5, and 7. Acute toxicity was mainly hematologic and was less severe with the lower hydroxyurea dose. Acute mucosal and skin toxicity was acceptable for all regimens. Late toxicity was noted in 4 of 17 patients who survived 12 months or more. Late effects were Radiation Therapy Oncology Group grade 3 or less. Fifteen of 35 patients achieved a complete response, and 11 of 35 patients achieved a partial response. The median survival rate was 10.5 months. There was no significant difference in responses or median survival between the groups. Reirradiation of head and neck cancer with 5-fluorouracil and hydroxyurea offers acceptable acute toxicity and minimal late effects. The clinical response rates and median survival are encouraging. Further investigation is warranted.

Postoperative radiotherapy with concurrent cisplatin appears to improve locoregional control of advanced, resectable head and neck cancers: RTOG 88-24.

PURPOSE: Despite aggressive surgery and postoperative radiation therapy, only 30% of patients who have advanced, potentially resectable carcinomas of the head and neck survive for 5 years. In the hope of improving this situation we studied the effect of postoperative radiotherapy delivered concurrently with cisplatin. METHODS AND MATERIALS: Patients who had Stage IV tumors and/or involved surgical margins received 60 Gy in 30 fractions over 6 weeks plus 100 mg/m2 of cisplatin on radiotherapy days 1, 23 and 43. Fifty-two patients participated in this trial and 51 were evaluated. Forty-three (84%) patients had pathologic T3 or T4 disease, 43 (84%) had Stage IV disease, and 27 (53%) had histologically involved surgical margins. RESULTS: Severe and life-threatening toxicities occurred in 20% and 12% of patients, respectively; the most common drug-related toxicities were leukopenia, anemia, nausea, and vomiting. Seventeen patients (43%) remain alive with no evidence of disease. Four patients (8%) died with no evidence of neoplastic disease, and one patient has died of a second independent malignancy. By actuarial analysis at 3 years, 48% of patients are alive, 81% have locoregional control of disease, and 57% are free of distant metastases. CONCLUSIONS: Based on comparison with similar patients treated in a prior Radiation Therapy Oncology Group/Intergroup trial (RTOG), we conclude that postoperative radiotherapy with concurrent cisplatin may improve locoregional control rates and should be prospectively tested.

Postsurgical recurrent carcinoma of the cervix: reassessment and results of radiation therapy options.

PURPOSE: To evaluate outcome and reassess the radiation therapy options in pelvic recurrences of cervical cancer treated initially with surgery. MATERIALS AND METHODS: In 30 patients, the prognostic factors analyzed for local control included site of recurrence (central, pelvic wall), tumor size, modality of radiation therapy, and radiation dose. Mean follow-up in survivors was 111.5 months. RESULTS: Local control was attained in (a) nine of 20 patients with central recurrence and in two of 10 with pelvic wall recurrence (p = .25); (b) none of four who received less than 50 Gy, five of nine who received 50-60 Gy, and six of 17 who received greater than 60 Gy (p = .27); and (c) five of 11 with tumor smaller than 3 cm, five of nine with tumor size 3-6 cm, and one of 10 with tumor larger than 6 cm. Multivariate analysis revealed a significant benefit of local control on survival (P = .05). Median survival for patients with central recurrence was 14.5 months compared with 9 months for those with pelvic wall recurrence. CONCLUSION: Local pelvic control depends on site and size of recurrence and radiation therapy modality and dose. Appropriate choice of brachytherapy modality is important. To improve local control and survival, more aggressive treatment is indicated, but attendant higher complications may be expected.

Effects of total lymphoid irradiation on SIV-infected macaques.

The identification of antiretroviral drugs that prevent, or delay for extended periods, progression of HIV-related disease has been of limited success. Because the number of HIV-infected people continues to increase, other therapeutic approaches must be tested. Using simian immunodeficiency virus (SIV)-infected macaques in a feasibility study, total lymphoid irradiation (TLI) was administered in fractionated doses to the supradiaphragmatic and then the infradiaphragmatic lymph nodes until a cumulative dose of 34.2 Gy was achieved in each field. During treatment and for more than 1 year of follow-up, the effects of TLI on various virological, hematological, and immunological parameters were evaluated and compared to those of similarly treated, uninfected macaques. Despite sustained low numbers of CD4+ lymphocytes (< 100/microliters blood) during treatment, TLI was well tolerated, did not result in intercurrent infections, and more importantly, induced a transient decrease in viral burden and did not exacerbate disease. Remarkably, this lack of disease progression and apparent containment of SIV replication were maintained despite persistent failure of PBMCs to respond to mitogen stimulation. Because SIV (and HIV) requires activated lymphocytes to replicate, failure of PBMCs to respond fully to stimuli may have contributed to restricting virus replication. This idea was supported by in vitro experiments in which infection of PBMCs before TLI produced higher levels of cell-free SIV than those obtained during or after TLI. Last, repopulation of peripheral blood and lymph nodes with lymphocytes paralleled that observed in uninfected control animals. The results indicate that (1) immunosuppression alone is not sufficient to induce progression to AIDS, (2) SIV infection does not undermine the ability of the immune system to regenerate new cells during the clinically latent phase, and (3) further evaluation of TLI or other immunosuppressive regimens as potential therapies for HIV disease is warranted.

Total lymphoid irradiation in the treatment of early or recurrent heart transplant rejection.

PURPOSE: Recurrent acute cardiac allograft rejection is an important cause of repeat hospitalization and a major mode of mortality, particularly during the 6 months immediately following transplant. Total lymphoid irradiation (TLI) has been shown experimentally to induce a state of partial tolerance when administered prior to transplantation. Anecdotal reports of clinical experience have also suggested efficacy of TLI in treatment of recurrent cardiac rejection. The purpose of this study is to evaluate the safety and efficacy of TLI for treatment of early or recurrent heart transplant rejection. MATERIALS AND METHODS: Between January 1990 and June 1992, 49 patients postallograft cardiac transplant were given courses of TLI for treatment of early or recurrent rejection after conventional therapy with Methylprednisolone, antithymocyte globulin, OKT3, and methotrexate. Two patients failed to complete their therapy and were not evaluated. Two other patients received a second TLI course, making a total of 49 courses delivered. Indications for TLI were early rejection (n = 5), recurrent rejection (n = 38), and recurrent rejection with vasculitis (n = 6). The dose goal of the TLI protocol was 8 Gy in 10 fractions given twice weekly. Three separate fields were used to encompass all major lymph node-bearing areas. The actual mean dose was 7 Gy (range 2.4-8.4 Gy), and the duration of treatment was 8 to 106 days. These variations were secondary to leukopenia or thrombocytopenia. RESULTS: The mean posttransplant follow-up is 15 +/- 1.2 months (maximum 27 months). Among patients initiating TLI within 1 month posttransplant (n = 15), the rejection frequency decreased from 1.83 episodes/patient/month pre-TLI to 0.13 episodes/patient/month post-TLI (p < 0.001). For those who began TLI 1-3 months after transplant (n = 21), rejection decreased from 1.43 to 0.10 episodes/patient/month (p < 0.001). When TLI was started more than 3 months posttransplant (n = 11), the pre-TLI and post-TLI rejection frequencies were 0.67 and 0.07/patient/month (p < 0.001), respectively. The reduced post-TLI rejection frequencies were maintained to 24 months. There was no increase in the frequency of infection after TLI, nor were there any deaths during or immediately following TLI. CONCLUSION: Total lymphoid irradiation is a safe and effective adjunct for prolonged control of early or recurrent cardiac rejection. Bone marrow suppression is transient in nearly all patients and is not associated with an increased incidence of infection. The long-term benefits, possible late deleterious effects, and the potential role of TLI as induction therapy remain to be elucidated.

Major geometric variations between multiple high-dose-rate applications of brachytherapy in cancer of the cervix: frequency and types of variation.

PURPOSE: To evaluate major geometric variations in multiple intracavitary applications for carcinoma of the cervix. MATERIALS AND METHODS: Orthogonal radiographs were reviewed of 17 consecutive patients with carcinoma of the cervix treated with 70 applications of high-dose-rate brachytherapy. In seven patients, conscious sedation was used for all applications. In 10 patients, general anesthesia was used for the first application and conscious sedation for subsequent applications. Major geometric variation between applications in axis, length, and slippage in tandem placement and separation, packing, and slippage in colpostats placement were reviewed. A major variation was defined as more than 1.0-cm deviation. RESULTS: Major variations between applications occurred more commonly in colpostats placement than in tandem placement. For tandems, the rates of variation were 5.7% in axis, 4.3% in length, and 1.4% in slippage. For colpostats, rates of variation were 7.1% in separation, 25.7% in vaginal packing, and 7.1% in slippage. No consistent pattern of variation was found between applications except in vaginal packing. CONCLUSION: Awareness of geometric variations should improve proper placement of intracavitary applicators for brachytherapy.

Conventional four-field pelvic radiotherapy technique without computed tomography-treatment planning in cancer of the cervix: potential geographic miss and its impact on pelvic control.

PURPOSE: To evaluate the impact of inadequate margins on pelvic control using the conventional four-field pelvic portals without computed tomography (CT)-treatment planning. METHODS AND MATERIALS: Between 1986 and 1991, 34 patients with invasive cancer of the cervix were eligible for outcome study of conventional four-field radiation therapy (10 Stage I, 16 Stage II, 8 Stage III). The eligibility for this study includes four-field pelvic technique, definitive radiation therapy, and diagnostic CT scan of the pelvis. For this study, an inadequate margin is arbitrarily defined as < or = 1.0 cm of normal tissue around the CT-defined tumor volume. RESULTS: All 34 patients had adequate margins for anterio-posterior/posterio-anterior portals. However, 19 patients had an inadequate margin at the posterior border (S2-S3 interspace) and/or custom-shaped rectal block for lateral pelvic portals. Two patients had inadequate margins at the anterior border (level of symphysis pubis) due to an enlarged uterus. With a median follow-up of 36 months, pelvic control for adequate margins and inadequate margins was 100% and 71% for Stage IB disease and 88% and 50% for Stage IIB disease, respectively. However, pelvic control for Stage IIIB disease was 50% for both groups. There was no difference in total dose to point A or point B between the two groups. CONCLUSION: Our preliminary data show higher local failure in patients with an inadequate margin. For four-field pelvic radiation therapy, we strongly recommend CT-treatment planning. Otherwise, anterio-posterior/posterio-anterior pelvic therapy is the most reliable treatment for cancer of the uterine cervix.

A clinically practical electron cone for the treatment of head and neck cancer.

PURPOSE: The purpose of the work was to develop a practical electron cone and to compare its dosimetry with that of the conventional applicator collimation system. METHODS AND MATERIALS: The electron cone consists of the upper part of a manufacturer-supplied electron applicator and an institution-built rectangular extension tube which produces a 12 cm x 6 cm field at 100 cm SSD while maintaining an air gap of 5 cm between the patient. RESULTS: The compact size of the cone allows electron irradiation without having to reposition the patient after photon treatment. The radiation field is very similar to that of a standard 15 cm x 15 cm applicator with a 12 cm x 6 cm field restricting insert. Radiation leakage at the surface of the special cone is typically less than 1% of the useful beam at dmax. During 12 years of clinical use the special cone proved itself very practical in the treatment of more than 300 patients. CONCLUSION: An electron cone practical for clinical use with dosimetry comparable to the conventional applicator was developed.

Conventional four-field pelvic radiotherapy technique without CT treatment planning in cancer of the cervix: potential geographic miss.

The advantage of 4-field radiation to the pelvis is the use of lateral ports which spare the small bowel anteriorly and a portion of the rectum posteriorly from radiation. However, guidelines for the lateral pelvic ports are poorly defined. This is a comparative analysis to determine adequate margins by correlating conventional lateral pelvic treatment portals with CT defined tumor volume. The study included 52 patients treated definitively for carcinoma of the uterine cervix between 1986 and 1991. The most common site of inadequate margin (< or = 1.0 cm) was at the rectal block. The incidence of inadequate margin ranged from 39% to 50% and was independent of the stage of the disease except non-bulky stage IB disease. The next most common site was at the posterior border where frequency of inadequate margin for cervical tumor depended on stage with 8% of stage IB, 27% of stage IIB and 22% of stage IIIB/IVA disease. For the anterior border, an enlarged uterus was the only reason for inadequate margin rather than cervical tumor in 8% of stage IB, 18% of stage IIB, and 27% of stage IIIB/IVA disease. Without knowledge of precise tumor volume, the 4-field pelvic technique is potentially dangerous, risking underdosing of the tumor volume. For 4-field pelvic radiotherapy, we strongly recommend CT treatment planning.

Malignant epidural spinal cord compression associated with a paravertebral mass: its radiotherapeutic outcome on radiosensitivity.

PURPOSE: To evaluate clinical characteristics and functional outcome of malignant epidural spinal cord compression associated with a paravertebral mass. METHODS AND MATERIALS: Between 1987 and 1990, 136 patients with epidural spinal cord compression were treated with irradiation. Of these, 25 patients (18%) had epidural spinal cord compression associated with a paravertebral mass. This report is based on analysis of these 25 patients. Fourteen patients received 3000 cGy in 10 fractions. Seven received 4000 cGy in 16 fractions. Four received 2000 cGy in 5 fractions. Motor function was evaluated by five grades. RESULTS: Lung cancer accounted for the majority of epidural spinal cord compression with a paravertebral mass (60%) followed by lymphoma (8%) and kidney tumor (8%). This pattern of epidural spinal cord compression has a longer duration of pain before developing neurologic symptoms and has a high propensity of the upper thoracic spine involvement by an apical lung cancers. The functional outcome of radiation treatment reveals a significant difference between moderately radiosensitive tumors (lung, prostate, cervix, esophagus) and very radiosensitive tumor (lymphoma). None of the nonambulatory patients became ambulatory following radiotherapy except for the very radiosensitive tumors. Higher doses of radiation treatment (4000 cGy in 16 fractions) did not improve functional outcome. CONCLUSION: Due to the larger tumor burden, radiation treatment for epidural spinal cord compression associated with a paravertebral mass is not as effective as treatment of epidural spinal cord compression without a paravertebral mass except for the very radiosensitive tumor. Therefore, combined treatment modality might be beneficial for improving functional outcome.

Total lymphoid irradiation: is there a role in pediatric heart transplantation?

Total lymphoid irradiation (TLI) is an effective adjunct in the therapy of recurrent allograft rejection in adult patients. Between Jan. 3, 1990, and Feb. 5, 1992, TLI was used in 43 heart transplant patients 4 days to 67 months (mean, 6 months) after heart transplantation for recurrent allograft rejection. A mean TLI dose of 700 cGy (range, 40 to 1120 cGy-) was administered during a mean of 7 weeks with adjustment in overall dose and duration determined in part by leukopenia, thrombocytopenia, or both. Among patients who received TLI therapy within 1 month of transplantation (n = 12), the rejection rate decreased from 1.9 episodes per patient per month before TLI to 0.1 episodes per patient per month after TLI (p < 0.001). Sixty percent of patients had no further rejection episodes for 6 months after TLI. Peripheral blood mononuclear cells from two patients were specifically unreactive toward donor stimulator cells in mixed-lymphocyte cultures at 2.5 and 6 months after TLI. During this experience three pediatric patients (ages 10 to 17 years) received TLI at 0.5, 0.8, and 0.9 months after heart transplantation for recurrent allograft rejection. The total TLI dosage for each patient was 720, 800, and 800 cGy. The rejection frequency fell from 1.8 episodes per patient per month before TLI to 0.1 episodes after TLI (p < 0.01). During follow-up of 6 to 25 months after TLI, no adverse sequelae of TLI were identified.(ABSTRACT TRUNCATED AT 250 WORDS)

A phase I study of high-dose cisplatin, prolonged infusion 5-fluorouracil, and concomitant conventional fraction radiation therapy in patients with inoperable squamous cell carcinoma of the head and neck.

Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been used alone, in combination, and in various doses and sequences with radiation therapy in attempts to improve local control and survival of patients with advanced head and neck cancer. This study was undertaken to determine the toxicity and maximum tolerated dose of high-dose CDDP plus prolonged infusion 5-FU with concomitant conventional radiation therapy. Twenty-two patients with inoperable Stage III and IV squamous cell cancer were treated with CDDP (30 or 35 mg/m2 for 5 days every 4 weeks for three courses) and 5-FU (200 or 300 mg/m2 per day continuous i.v. infusion for 12 weeks) with concomitant conventional radiation therapy. This aggressive treatment regimen is accompanied by severe mucositis, myelosuppression, and chronic neuropathy. CDDP, 35 mg/m2/day x 5, and 200 mg/m2/day of 5-FU infused over 12 weeks were identified as potential doses for future Phase II studies.

Total lymphoid irradiation in the treatment of early or recurrent heart rejection.

UNLABELLED: Total lymphoid irradiation (TLI) has been shown experimentally to induce a state of partial tolerance when administered before organ transplantation. Anecdotal reports in clinical transplantation have suggested efficacy of TLI in the treatment of recurrent rejection after heart transplantation. To further assess the safety and efficacy of TLI, 19 patients were entered into a protocol of TLI for the treatment of recurrent or early severe rejection despite conventional therapy. Rejection rate decreased from 1.3 episodes/month before TLI to 0.53 during TLI and 0.07 after TLI (p < 0.0001). Infections increased during TLI (possibly related to recent augmented immunosuppression before TLI), but all infections were successfully treated. One death occurred after TLI from acute allograft rejection. White blood cell (WBC) and platelet counts were depressed during and after (3 months) TLI. Frequent adjustments of dosing interval and, occasionally of the dosage were required to control WBC and platelet counts. Five patients experienced transient WBC of less than 1000/ml. More rejection episodes (and thus greater overall immunosuppression) before TLI and a lower tolerated dose of azathioprine before TLI predicted (by multivariate analysis) a lower WBC during TLI. CONCLUSIONS: (1) TLI is an effective adjunct for the intermediate control of early or recurring acute allograft rejection. (2) Close surveillance of WBC and platelets with appropriate adjustment of TLI dose and interval is necessary during TLI therapy. (3) The long-term benefits, possible late deleterious effects, and potential role of TLI as induction therapy remain to be elucidated.

Treatment of recurrent head and neck cancer with 5-fluorouracil, hydroxyurea, and reirradiation.

Head and neck cancer locally recurrent after previous irradiation and surgery presents a difficult management problem. Conventional treatment alternatives include chemotherapy, reirradiation with interstitial implant, and hyperthermia. Reirradiation with external beam is generally not considered because of previous high radiation dose and limited tissue tolerance. In this study, 21 patients with recurrent and previously irradiated head and neck cancer were treated in a Phase I-II fashion. Patients received 5 days of 5-fluorouracil, 300 mg/m2/day IV bolus, Hydroxyurea 1.5 or 2 g/day by mouth and external beam radiation therapy every 2 weeks for up to four courses. Of 20 evaluable patients, 9 have attained a complete response (CR) and 6 a partial response (PR). Fifteen patients completed all planned therapy, eight on time, seven patients with delays. With a median follow-up of 7 months, 13 patients are alive, 7 disease-free (3 after salvage surgery) and 6 with recurrence. Eight patients have died. The 1-year survival is 56%. Treatment toxicity was mainly neutropenia. No major early or late radiation related side effects have been observed at a median follow-up of 7 months. Neither previous radiation dose, time since first radiation, prior chemotherapy, or site of recurrence was predictive of response or treatment tolerance. Patients with a performance status of at least 80 had a significant higher CR rate, with 7/10 patients in this group, as compared to 2/10 patients in patients with a performance status less than 80, achieving a CR. Reirradiation with 5-fluorouracil and hydroxyurea is a well tolerated outpatient treatment program for patients with recurrent and previous irradiated head and neck cancer that produces a high response rate and can provide significant palliation of symptoms.

Early-stage glottic cancer: importance of dose fractionation in radiation therapy.

The treatment results in 85 patients with T1N0M0 squamous cell carcinoma of the glottic larynx who were treated with primary radiation therapy were reviewed to analyze for local control. After a minimum follow-up period of 2 years, 13 patients had local recurrence of disease, which yielded a local control rate of 84.7%. Local control was then reassessed as a function of substages (T1a and T1b) and dose fractionation. No difference in local control was seen in T1a and T1b neoplasms. However, after undergoing standard once-a-day fractionation, patients treated with fractions of 200 cGy had a local control rate of 96%, while those receiving 180 cGy had a local control rate of 79% (P = .05). Mean total dose for each patient group was comparable, and the median number of days of treatment interruption was the same for both groups. These data corroborate the recent findings of other authors regarding the importance of fraction size in facilitating local control of early-stage glottic cancer.

Expedient set-up of tangential breast fields with a simple gantry attachment.

A novel technique for setting up tangential fields is described. The technique uses a simple device (Breast Aligner) which attaches to the collimator of the treatment unit. The function of the Breast Aligner is similar to conventional front and back pointers except that the beam edge rather than central ray is defined. By delineating beam entrance and exit points at the posterior field edge, the device greatly simplifies and expedites set-up, and enhances precision of port alignment. Additional advantageous features include: (a) the ability to compensate for small inadvertent variations from the initial set-up position or for patient movement between the set-up of opposing ports, (b) the ability to visually check port alignment in the treatment position immediately before irradiation, and (c) decreased chance of human and equipment error by eliminating the need for measurements and calculations at the time of treatment. Our method can be used for SSD or SAD techniques and, with minor adjustment, is applicable for establishment of coplanar cephalad field borders as required at the junction of a supraclavicular field.

A phase I study of prolonged infusion 5-fluorouracil and concomitant radiation therapy in patients with squamous cell cancer of the head and neck.

The radiosensitization properties of 5-FU are well documented, and clinical trials have suggested improved local control and survival in head and neck cancer. Clinical trials to date have used bolus injection or short term (less than or equal to 5 days) 5-FU infusions. To determine the maximum tolerated dose (MTD) of 5-FU given as continuous intravenous infusion for 12 weeks concomitant with conventional radiation therapy, 18 patients with advanced inoperable head and neck cancers were treated with conventional irradiation and 100, 200, 250, or 300 mg/m2/day of 5-FU. A dose of 250 mg/m2/day was determined to be the maximum tolerated dose and is recommended for Phase II studies.