Three-dimensional conformal radiation treatment planning and delivery for low- and intermediate-grade gliomas.

Three-Dimensional conformal radiation treatment (3D-CRT) planning and delivery is an external beam radiation therapy modality that has the general goal of conforming the shape of a prescribed dose volume to the shape of a 3-dimensional target volume, simultaneously limiting dose to critical normal structures. 3-Dimensional conformal therapy should include at least one volumetric imaging study of the patient. This image should be obtained in the treatment position for visualizing the target and normal anatomic structures that are potentially within the irradiated volume. Most often, computed tomography (CT) and/or magnetic resonance imaging (MRI) are used; however, recently, other imaging modalities such as functional MRI, MR spectroscopy, and positron emission tomography (PET) scans have been used to visualize the clinically relevant volumes. This article will address the clinically relevant issues with regard to low- and intermediate-grade gliomas and the role of 3D-CRT planning. Specific issues that will be addressed will include normal tissue tolerance, target definition, treatment field design in regard to isodose curves and dose-volume histograms, and immobilization.

Induction therapy with carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal radiotherapy in the treatment of locally advanced, unresectable non-small cell lung cancer: preliminary report of a phase I trial.

Locally advanced non-small cell lung cancer is optimally managed with chemotherapy and thoracic irradiation, although the most appropriate strategy is not yet defined. In this phase I trial, we use two 21-day cycles of induction chemotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (225 mg/m2 over 3 hours) and carboplatin (area under the concentration-time curve = 6) followed by concurrent weekly paclitaxel (45 mg/m2/wk x 6) and carboplatin (area under the concentration-time curve = 2/wk x 6) and thoracic irradiation. Patients undergo three-dimensional treatment planning (conformal radiotherapy) to define the cancer target volume precisely. The phase I question being addressed in this study is the maximum tolerated radiation dose given concurrently with low-dose paclitaxel and carboplatin. The initial radiation dose is 60 Gy, with dose escalations to 66 Gy, 70 Gy, and 74 Gy being planned. Ten patients have been entered thus far (eight men and two women). Their median age is 67 years (range, 59 to 78 years), and none of the patients has had greater than 5% pretreatment weight loss. Seven of 10 are evaluable for response to induction carboplatin and paclitaxel, with a response rate of 57% (three partial responses and one minor response). Three patients had stable disease and none of the patients had evidence of progressive disease during induction chemotherapy. Three patients have completed all treatment at 60 Gy and one has completed all treatment at 66 Gy. Three of the four patients have had partial responses (75%), with the remaining patient having stable disease. Toxicity in the concurrent chemoradiotherapy portion of the trial thus far has consisted of grade 3 neutropenia in one patient and grade 4 lymphocytopenia in all four patients. No grade 3 or 4 nonhematologic toxicity has been seen. The trial data are not yet mature enough to report on survival. Accrual and treatment is continuing at the 66 Gy radiation dose level.

Retrospective reconstruction of three-dimensional radiotherapy treatment plans of the thorax from two dimensional planning data.

PURPOSE: A method for the retrospective reconstruction of three-dimensional (3-D) radiotherapy treatment plans from two-dimensional (2-D) planning data is detailed in this paper. METHODS AND MATERIALS: With these techniques the user can register an arbitrarily shaped portal on a simulation film with a diagnostic computed tomography study of the patient and then generate the resultant 3-D dose distribution or dose-volume histogram. Seven treatment plans were reconstructed of patients who had previously undergone 3-D treatment planning for fields involving the thorax and who had had a diagnostic computed tomography (CT) scan. The dose-volume histograms and the spatial positions of the beams on the reconstructed plans were then compared to those of the original 3-D plan, which until then, were not made available to the investigators. RESULTS: The dose-volume histograms of the reconstructed plans did not differ from those of the original plans by more than 3% except in the low dose region. The error in positioning the beam in the reconstructed plan was determined to be approximately 5 mm. CONCLUSION: The technique of 3-D treatment plan reconstruction can be used, through retrospective studies, to obtain better assessments of normal tissue complication probabilities and tumor control probabilities.

Image registration: an essential part of radiation therapy treatment planning.

PURPOSE: We believe that a three-dimensional (3D) registration of nonplanning (diagnostic) imaging data with the planning computed tomography (CT) offers a substantial improvement in tumor target identification for many radiation therapy patients. The purpose of this article is to review and discuss our experience to date. METHODS AND MATERIALS: We reviewed the charts and treatment planning records of all patients that underwent 3D radiation treatment planning in our department from June 1994 to December 1995, to learn which patients had image registration performed and why it was thought they would benefit from this approach. We also measured how much error would have been introduced into the target definition if the nonplanning imaging data had not been available and only the planning CT had been used. RESULTS: Between June 1994 and December 1995, 106 of 246 (43%) of patients undergoing 3D treatment planning had image registration. Four reasons for performing registration were identified. First, some tumor volumes have better definition on magnetic resonance imaging (MRI) than on CT. Second, a properly contrasted diagnostic CT sometimes can show the tumor target better than can the planning CT. Third, the diagnostic CT or MR may have been preoperative, with the postoperative planning CT no longer showing the tumor. Fourth, the patient may have undergone cytoreductive chemotherapy so that the postchemotherapy planning CT no longer showed the original tumor volume. In patients in whom the planning CT did not show the tumor volume well an analysis was done to determine how the treatment plan was changed with the addition of a better tumor-defining nonplanning CT or MR. We have found that the use of this additional imaging modality changed the tumor location in the treatment plan at least 1.5 cm for half of the patients, and up to 3.0 cm for 1/4 of the patients. CONCLUSIONS: Multimodality and/or sequential imaging can substantially aid in better tumor definition in many patients undergoing 3D treatment planning. In some patients the appropriate nonplanning imaging source can change the perceived tumor location by several centimeters and is thus essential for proper treatment planning.

Invasive carcinoma of the uterine cervix in women age 25 or less.

The incidence of cervix cancer in young women appears to be increasing. However, the influence of young age on prognosis remains unknown. There is almost no information on the prognosis of very young women, age 25 years or less, with invasive cervical carcinoma. From April 1969 to June 1987, 40/2195 (1.8%) patients, age 25 years or less, with invasive carcinoma of the uterine cervix were diagnosed, staged, and treated at our institution. Median age was 24.7 years (range 20.7 to 25.9 years). Distribution by FIGO stage was: Stage IA 7 (18%), Stage IB 23 (58%), Stage II 4 (10%), Stage III 4 (10%), and Stage IVA 2 (4%). Thirty-four (85%) patients had squamous cell carcinoma and six (15%) had adenocarcinoma. Treatment consisted of radical hysterectomy for all Stage IA patients, radical hysterectomy with or without bilateral pelvic node dissection for the 12 early Stage IB patients, and radiation with or without surgery for the remaining 11 Stage IB patients and all Stage II-IVA patients. Median follow-up was 122 months (range 13.2-190.6 months). Five-year disease-free survival rates were: Stage IA 100%; Stage IB 54.8%; and Stage II-IVA 13.7%. Five-year disease-free survival for the Stage IB patients with squamous cell carcinoma age 25 years or less was 64.7%, compared with 83% for women of all ages with Stage IB squamous histology treated at our institution. Seven of 23 Stage IB patients suffered regional recurrence only, one a local recurrence only, one a distant recurrence only, and one a combined recurrence. Seventy-five percent of these patients presented with Stage I disease; however, one-third died from their disease. The major site of failure was in the pelvis only. This, coupled with the low risk of long-term serious complications, suggests that more aggressive pelvic therapy may result in improved disease-free survival.

Improving treatment planning accuracy through multimodality imaging.

PURPOSE: In clinical practice, physicians are constantly comparing multiple images taken at various times during the patient's treatment course. One goal of such a comparison is to accurately define the gross tumor volume (GTV). The introduction of three-dimensional treatment planning has greatly enhanced the ability to define the GTV, but there are times when the GTV is not visible on the treatment-planning computed tomography (CT) scan. We have modified our treatment-planning software to allow for interactive display of multiple, registered images that enhance the physician's ability to accurately determine the GTV. METHODS AND MATERIALS: Images are registered using interactive tools developed at the University of North Carolina at Chapel Hill (UNC). Automated methods are also available. Images registered with the treatment-planning CT scan are digitized from film. After a physician has approved the registration, the registered images are made available to the treatment-planning software. Structures and volumes of interest are contoured on all images. In the beam's eye view, wire loop representations of these structures can be visualized from all image types simultaneously. Each registered image can be seamlessly viewed during the treatment-planning process, and all contours from all image types can be seen on any registered image. A beam may, therefore, be designed based on any contour. RESULTS: Nineteen patients have been planned and treated using multimodality imaging from November 1993 through August 1994. All registered images were digitized from film, and many were from outside institutions. Brain has been the most common site (12), but the techniques of registration and image display have also been used for the thorax (4), abdomen (2), and extremity (1). The registered image has been an magnetic resonance (MR) scan in 15 cases and a diagnostic CT scan in 5 cases. In one case, sequential MRs, one before treatment and another after 30 Gy, were used to plan patient's initial fields and boost, respectively. Case illustrations are shown. CONCLUSIONS: We have successfully integrated multimodality imaging into our treatment-planning system, and its routine use is increasing. Multimodality imaging holds out the promise of improving treatment planning accuracy and, thus, takes maximum advantage of three dimensional treatment planning systems.

A comparison of postoperative techniques for carcinomas of the larynx and hypopharynx using 3-D dose distributions.

If a head and neck cancer originates low in the neck with a primary site below the shoulders, a technical challenge to the radiation oncologist exists in that the entire neck needs treatment while avoiding overlap of multiple fields on the spinal cord. No standard solution to this problem exists. We have developed a 3-D treatment planning tool that can be used to develop and compare 3-D treatment plans and dose distributions. Using this tool, we have studied the following techniques for the postoperative treatment of carcinomas of the larynx and hypopharynx, tumors that often embody the problems discussed above: (a) the mini-mantle technique used at the Massachussetts General Hospital, (b) a 3-field technique used at the University of Florida at Gainesville (UF 3-field), (c) a 3-field technique used at our institution and at many others (standard 3-field), and (d) the kicked out lateral technique used at our institution and at others. The 3-D dose distributions from these plans are compared. With 100% delivered just anterior to the vertebral body at mid-neck, the mini-mantle technique results in large 120% hot spots laterally and anteriorly in the neck. Near the mastoid tips, however, the dose falls to 100%. The upper neck nodes may be underdosed since this is 20% cooler than the lateral-anterior neck dose (where a large 120% hot spot exists). The spinal cord is adequately blocked. The two 3-field techniques result in small hot spots at the junction of the lateral and anterior fields. Because different methods are used to prevent overlap at the spinal cord, these hot spots occur anteriorly in the standard 3-field technique and laterally in the UF 3-field technique. The spinal cord block results in untreated neck tissue which can be supplemented with electrons in the standard 3-field technique, but is left untreated in the UF 3-field technique. Both techniques result in a generous length of spinal cord which does not receive full dose. The kicked out lateral technique treats the entire neck and reconstructed pharynx without matching fields at midneck. The upper mid mediastinum is underdosed 10-20% despite being within the posterior inferior portion of the beam. This could be minimized by using a tissue compensator. Unless there is significant subglottic extension or significant risk of disease in the upper mediastinum, we favor treating these malignancies with the kicked out lateral technique, which avoids the problem of junctioning lateral and anterior fields and provides a fairly homogeneous dose distribution.

Portfolio: a prototype workstation for development and evaluation of tools for analysis and management of digital portal images.

PURPOSE: The purpose of this investigation was to design and implement a prototype physician workstation, called PortFolio, as a platform for developing and evaluating, by means of controlled observer studies, user interfaces and interactive tools for analyzing and managing digital portal images. The first observer study was designed to measure physician acceptance of workstation technology, as an alternative to a view box, for inspection and analysis of portal images for detection of treatment setup errors. METHODS AND MATERIALS: The observer study was conducted in a controlled experimental setting to evaluate physician acceptance of the prototype workstation technology exemplified by PortFolio. PortFolio incorporates a windows user interface, a compact kit of carefully selected image analysis tools, and an object-oriented data base infrastructure. The kit evaluated in the observer study included tools for contrast enhancement, registration, and multimodal image visualization. Acceptance was measured in the context of performing portal image analysis in a structured protocol designed to simulate clinical practice. The acceptability and usage patterns were measured from semistructured questionnaires and logs of user interactions. RESULTS: Radiation oncologists, the subjects for this study, perceived the tools in PortFolio to be acceptable clinical aids. Concerns were expressed regarding user efficiency, particularly with respect to the image registration tools. CONCLUSIONS: The results of our observer study indicate that workstation technology is acceptable to radiation oncologists as an alternative to a view box for clinical detection of setup errors from digital portal images. Improvements in implementation, including more tools and a greater degree of automation in the image analysis tasks, are needed to make PortFolio more clinically practical.

Digitally reconstructed fluoroscopy and other interactive volume visualizations in 3-D treatment planning.

PURPOSE: Add radiographic context to the beam's-eye-view used in 3-dimensional treatment planning. Improve methods for interactive visualization of anatomy and dose distributions. METHODS AND MATERIALS: Most 3-dimensional treatment planning systems feature a beam's-eye view that includes only graphical representations of patient anatomy. With input devices such as a mouse or trackball, the user interactively shapes the treatment field using the graphical models to provide geometric information. Radiographic context provides additional geometric information important for determining field shape. We have implemented digitally reconstructed fluoroscopy in the beam's-eye view by increasing the efficiency for computing digitally reconstructed radiographs. In addition we have improved algorithms for real-time surface and volume rendering for anatomy and doses using an experimental graphics supercomputer. RESULTS: Without radiographic context in the beam's-eye-view, field shapes were sometimes changed after simulation or portal images were obtained. Digitally reconstructed fluoroscopy has essentially eliminated these changes. Higher quality interactive three-dimensional displays improve the comprehension, confidence and efficiency of the user. Our improvements have already been implemented on one model of a new generation of commercial graphics workstations. CONCLUSION: Addition of radiographic context to the beam's-eye-view is recommended. Incorporation of higher quality interactive graphics is rapidly becoming practical and is encouraged.

A portable software tool for computing digitally reconstructed radiographs.

PURPOSE: To develop a portable software tool for fast computation of digitally reconstructed radiographs (DRR) with a friendly user interface and versatile image format and display options. To provide a means for interfacing with commercial and custom three-dimensional (3D) treatment planning systems. To make the tool freely available to the Radiation Oncology community. METHODS AND MATERIALS: A computer program for computing DRRs was enhanced with new features and rewritten to increase computational efficiency. A graphical user interface was added to improve ease of data input and DRR display. Installer, programmer, and user manuals were written, and installation test data sets were developed. The code conforms to the specifications of the Cooperative Working Group (CWG) of the National Cancer Institute (NCI) Contract on Radiotherapy Treatment Planning Tools. RESULTS: The interface allows the user to select DRR input data and image formats primarily by point-and-click mouse operations. Digitally reconstructed radiograph formats are predefined by configuration files that specify 19 calculation parameters. Enhancements include improved contrast resolution for visualizing surgical clips, an extended source model to stimulate the penumbra region in a computed port film, and the ability to easily modify the CT numbers of objects contoured on the planning computed tomography (CT) scans. CONCLUSIONS: The DRR tool can be used with 3D planning systems that lack this functionality, or perhaps improve the quality and functionality of existing DRR software. The tool can be interfaced to 3D planning systems that run on most modern graphics workstations, and can also function as a stand-alone program.

The tetrad and hexad: maximum beam separation as a starting point for noncoplanar 3D treatment planning: prostate cancer as a test case.

PURPOSE: In contrast to computer optimized three-dimensional (3D) treatment planning, we have used maximally separated, noncoplanar beams as the starting point for 3D treatment planning of prostate cancer to maximize the rate of dose fall off from the target volume and minimize dose to surrounding tissues. MATERIALS AND METHODS: A planar four-field plan, a planar six-field plan, a tetrad plan, and a hexad plan are analyzed using a 3D treatment planning system which is capable of displaying real-time 3D dose distributions within volume reconstructed data sets (VISTAnet--an extension of the virtual simulator). The tetrad plan is based on the methane molecule and the hexad plan has a minimum separation of 58 degrees on beam entrance. All fields are conformal. The irradiated volume equals the clinical target volume plus a 1 cm margin. Competing plans are compared using cumulative dose-volume histograms and normal tissue complication probabilities. RESULTS: The crossover point, the isodose surface that conforms more to the beams than the target, is introduced and described. The hexad and tetrad plans result in tighter dose distributions when compared to the planar plans with the same number of beams. The tetrad plan treats a volume less than or equal to the planar six-field plan at isodose surfaces above 18% except between 37% and 44% where the tetrad volume is slightly larger. As expected from integral dose considerations, the amount of normal tissue receiving some radiation increases, but the amount receiving clinically significant amounts of radiation decreases as the number of beams increase. The plan involving the largest number of noncoplanar beams results in the tightest isodose distribution. Analysis of rectal and bladder cumulative dose volume histograms does not reveal a clearly superior plan based on normal tissue complication probabilities. CONCLUSIONS: Using basic principles of solid geometry, maximally separated beams without significant overlap on exit or entrance can be designed which minimize clinically significant dose to surrounding tissues and tighten the isodose distribution around the target volume. The emphasis of this treatment plan optimization is geometric in contrast to methods using computer optimization or artificial intelligence.

An integrated system for interstitial 192Ir implants.

An efficient system for preparing, afterloading, and removing interstitial 192Ir strands has been developed. Use of the system reduces the risk of personnel exposure and eliminates some patient discomfort. The system is "integrated" in that all aspects of the implantation process are considered, from source preparation to source removal. Strand preparation is facilitated by an "assembly line" process using shielded equipment. Components include a handling block for measuring and cutting active strands, a mirror, and a transport container. Afterloading and removal techniques use quick release devices and several forms of afterloading tubing and catheters, each terminated by a Luer lock adapter. Both blind-end and through-and-through implants are possible. Each 192Ir strand, threaded through an injection cap that mates with the Luer lock adapter, is quickly inserted into its tubing or catheter and locked into place. No crimping is required and no additional positioning of the sources is needed. Strand removal is easily accomplished by unlocking and removing the injection cap. The strands receive no mechanical damage and can be reused after appropriate cleaning. More than 100 cases have been performed without incident. Applications include head/neck, breast, and template and non-template vaginal wall treatments.

1000 cGy single dose palliation for advanced carcinoma of the cervix or endometrium.

Between January 1980 and the present, 42 patients with symptomatic, incurable gynecologic malignancies were treated at the University of North Carolina with 1000 cGy in a single fraction to the pelvis, repeated once or twice at monthly intervals as necessary. Of patients with adequate follow-up, total cessation of bleeding was seen in 18 of 30 (60%), complete pain relief in 2/9 (22%), and complete tumor eradication in 7/28 (25%). These palliative benefits were permanent in approximately half of the patients. Five serious treatment complications have been documented, four occurred more than 10 months after treatment. We conclude that 1000 cGy single-fraction whole pelvis treatment can be an effective means of palliating advanced gynecologic cancer provided the patient has a life expectancy of less than 1 year. Patients with a longer life expectancy are at risk for both recurrence of symptoms and for treatment related complications.

VISTAnet: interactive real-time calculation and display of 3-dimensional radiation dose: an application of gigabit networking.

Three-dimensional treatment planning can allow the clinician to create plans that are highly individualized for each patient. However, in lifting the constraints traditionally imposed by 2-dimensional planning, the clinician is faced with the need to compare a much larger number of plans. Although methods to automate that process are being developed, it is not yet clear how well they will perform. VISTAnet is a 3 year collaborative effort between the Departments of Radiation Oncology and Computer Science at the University of North Carolina, the North Carolina Supercomputing Center, BellSouth, and GTE with the medical goal of providing real-time 3-dimensional radiation dose calculation and display. With VISTAnet technology and resources, the user can inspect 3-dimensional treatment plans in real-time along with the associated dose volume histograms and can fine tune these plans in real-time with regard to beam position, weighting, wedging, and shape. Thus VISTAnet provides an alternate and, possibly, complementary approach to computerized searches for optimal radiation treatment plans. Building this system has required the development of very fast radiation dose code, methods for simultaneously manipulating and modifying multiple radiation beams, and new visualizations of 3-dimensional dose distributions.

Feasibility of optimizing the dose distribution in lung tumors using fluorine-18-fluorodeoxyglucose positron emission tomography and single photon emission computed tomography guided dose prescriptions.

The information provided by functional images may be used to guide radiotherapy planning by identifying regions that require higher radiation dose. In this work we investigate the dosimetric feasibility of delivering dose to lung tumors in proportion to the fluorine-18-fluorodeoxyglucose activity distribution from positron emission tomography (FDG-PET). The rationale for delivering dose in proportion to the tumor FDG-PET activity distribution is based on studies showing that FDG uptake is correlated to tumor cell proliferation rate, which is shown to imply that this dose delivery strategy is theoretically capable of providing the same duration of local control at all voxels in tumor. Target dose delivery was constrained by single photon emission computed tomography (SPECT) maps of normal lung perfusion, which restricted irradiation of highly perfused lung and imposed dose-function constraints. Dose-volume constraints were imposed on all other critical structures. All dose-volume/function constraints were considered to be soft, i.e., critical structure doses corresponding to volume/function constraint levels were minimized while satisfying the target prescription, thus permitting critical structure doses to minimally exceed dose constraint levels. An intensity modulation optimization methodology was developed to deliver this radiation, and applied to two lung cancer patients. Dosimetric feasibility was assessed by comparing spatially normalized dose-volume histograms from the nonuniform dose prescription (FDG-PET proportional) to those from a uniform dose prescription with equivalent tumor integral dose. In both patients, the optimization was capable of delivering the nonuniform target prescription with the same ease as the uniform target prescription, despite SPECT restrictions that effectively diverted dose from high to low perfused normal lung. In one patient, both prescriptions incurred similar critical structure dosages, below dose-volume/function limits. However, in the other patient, critical structure dosage from the nonuniform dose prescription exceeded dose-volume/function limits, and greatly exceeded that from the uniform dose prescription. Strict compliance to dose-volume/ function limits would entail reducing dose proportionality to the FDG-PET activity distribution, thereby theoretically reducing the duration of local control. Thus, even though it appears feasible to tailor lung tumor dose to the FDG-PET activity distribution, despite SPECT restrictions, strict adherence to dose-volume/function limits could compromise the effectiveness of functional image guided radiotherapy.

Three-dimensional high-resolution volume rendering (HRVR) of computed tomography data: applications to otolaryngology-head and neck surgery.

Conventional computed tomographic display formats are not optimal for demonstrating three-dimensional anatomic relationships. In otolaryngology--head and neck surgery these critical relationships are often highly complex, and their complete understanding is essential to a successful surgical outcome. A new computer-generated image display format, high-resolution volume rendering (HRVR), facilities the understanding of these critical anatomic relationships by transforming conventional imaging data into clinically relevant 3-D images. Unlike many other 3-D reconstruction algorithms, HRVR suffers minimal data loss in the conversion process, which in turn provides for superior image resolution. This better allows the application of 3-D technology to small or complicated anatomic structures such as those frequently encountered in otolaryngology--head and neck surgery. Advances in computer-controlled manipulations that further enhance the evaluation of desired pathologic features have been achieved. This pilot study contains representative clinical cases chosen to illustrate the potential utility of HRVR in otolaryngology--head and neck surgery. The authors believe HRVR images will enhance the surgeon's understanding of the 3-D anatomic relationships that exist between critical pathologic features and surrounding vital structures.

Treatment of the clinically negative neck in advanced cancer of the head and neck.

The proper management of the clinically negative neck in primary squamous cell carcinomas of the head and neck remains controversial. Although many clinicians believe that elective neck dissection or neck irradiation are equally effective for controlling subclinical disease, previous studies have not directly addressed this question. The charts of 195 patients with advanced primary squamous carcinoma, yet with clinically negative necks, were reviewed. There were no significant differences in the rates of neck cancer recurrence among the elective neck irradiation, dissection, and combined treatment groups. Elective neck irradiation and neck dissection in patients with clinically negative nodes seemed equivalent in their ability to control neck disease. The decision as to which form of therapy is preferable must therefore be based on other criteria.

Simultaneous chemoradiation in the treatment of advanced head and neck cancer.

Fifty-eight patients with either advanced or unresectable squamous cell carcinoma of the head and neck were randomly selected to receive either twice daily radiation alone or twice daily radiation plus concomitant chemotherapy with cisplatin and fluorouracil (5-fluorouracil). There was no advantage in survival or time to progression with the addition of chemotherapy to twice daily radiation for patients with advanced resectable cancers. In the group of patients with unresectable cancers, however, there was a statistically significant advantage to the addition of chemotherapy, both in terms of disease-free survival and date to progression.

Chemoradiation for locally advanced squamous cell carcinoma of the head and neck for organ preservation and palliation.

OBJECTIVES: To measure the efficacy and toxic effects of our chemoradiotherapy regimen by means of response and survival in patients with advanced squamous cell carcinoma of the head and neck (HNSCC) for organ preservation in resectable disease or palliation in unresectable disease. DESIGN: All patients underwent evaluation by the multidisciplinary head and neck cancer team, with pathological diagnosis and staging. All patients underwent assessment for response to therapy using results of physical examination and radiologic imaging. Patients were followed up at 3-month intervals for a planned period of 5 years. SETTING: Academic center. PATIENTS: Thirty-eight previously untreated patients with newly diagnosed HNSCC were treated from June 1, 1996, through December 31, 1998, of whom 20 had resectable and 18 had unresectable tumors. INTERVENTION: Patients received intravenous cisplatin, 100 mg/m(2) for 1 hour on days 1 and 29; a 24-hour continuous infusion of fluorouracil, 1000 mg/m(2) on days 1 through 4 and 29 through 32; and radiation therapy, 150 rad twice daily for 12 days. The patients were given a 7- to 10-day break, and radiation therapy was restarted on day 29 for 12 additional days (total dose, 7200 rad). MAIN OUTCOME MEASURES: Complete, partial, and total response rates; disease-free survival; overall survival; and toxic effects. RESULTS: Toxic effects of treatment were moderately severe, including grades III to IV mucositis (89%), neutropenia (71%), and renal toxic effects (8%). In the 18 patients in the unresectable group, complete response in the 17 primary tumors and 15 cervical nodal metastases was achieved in 12 (71%) and 9 (60%), respectively; in the 20 patients undergoing organ preservation, complete response rates were 100% in the 23 primary tumors and 15 cervical nodal metastases. Complete response for all 38 patients was achieved in 31 (82%). In the unresectable group, the Kaplan-Meier relapse-free survival estimate is 56%, with follow-up from 29 to 45 months. In the organ preservation group, 75% of patients are alive without disease, and 8 have been followed up for 36 to 48 months. Of the 5 patients who have died, only 2 died of disease, with recurrences at 13.0 and 16.5 months. CONCLUSIONS: Chemoradiotherapy consisting of cisplatin, fluorouracil, and twice-daily external beam radiation is highly effective in achieving durable complete responses in patients with resectable HNSCC undergoing organ preservation and patients with unresectable HNSCC undergoing palliation. Toxic effects of this regimen were moderate to severe.