Association of Radiotherapy Duration With Clinical Outcomes in Patients With Esophageal Cancer Treated in NRG Oncology Trials: A Secondary Analysis of NRG Oncology Randomized Clinical Trials.

Importance: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes. Objective: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT). Design, Setting, and Participants: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology Group). Enrolled patients with nonmetastatic esophageal cancer underwent definitive CRT in the trials between 1986 and 2013, with follow-up occurring through 2014. Data analyses were conducted between March 2022 to February 2023. Exposures: Treatment groups in the trials used standard-dose RT (50 Gy) and concurrent chemotherapy. Main Outcomes and Measures: The outcomes were local-regional failure (LRF), distant failure, disease-free survival (DFS), and overall survival (OS). Multivariable models were used to examine the associations between these outcomes and both RT duration and interruptions. Radiotherapy duration was analyzed as a dichotomized variable using an X-Tile software to choose a cut point and its median value as a cut point, as well as a continuous variable. Results: The analysis included 509 patients (median [IQR] age, 64 [57-70] years; 418 males [82%]; and 376 White individuals [74%]). The median (IQR) follow-up was 4.01 (2.93-4.92) years for surviving patients. The median cut point of RT duration was 39 days or less in 271 patients (53%) vs more than 39 days in 238 patients (47%), and the X-Tile software cut point was 45 days or less in 446 patients (88%) vs more than 45 days in 63 patients (12%). Radiotherapy interruptions occurred in 207 patients (41%). Female (vs male) sex and other (vs White) race and ethnicity were associated with longer RT duration and RT interruptions. In the multivariable models, RT duration longer than 45 days was associated with inferior DFS (hazard ratio [HR], 1.34; 95% CI, 1.01-1.77; P = .04). The HR for OS was 1.33, but the results were not statistically significant (95% CI, 0.99-1.77; P = .05). Radiotherapy duration longer than 39 days (vs ≤39 days) was associated with a higher risk of LRF (HR, 1.32; 95% CI, 1.06-1.65; P = .01). As a continuous variable, RT duration (per 1 week increase) was associated with DFS failure (HR, 1.14; 95% CI, 1.01-1.28; P = .03). The HR for LRF 1.13, but the result was not statistically significant (95% CI, 0.99-1.28; P = .07). Conclusions and Relevance: Results of this study indicated that in patients with esophageal cancer receiving definitive CRT, prolonged RT duration was associated with inferior outcomes; female patients and those with other (vs White) race and ethnicity were more likely to have longer RT duration and experience RT interruptions. Radiotherapy interruptions should be minimized to optimize outcomes.

Pilot Study of External Beam Radiotherapy for Recurrent Unremitting Tracheal Stenosis.

OBJECTIVE: Tracheal stenosis can have a variety of presentations, severities, causes, and be a difficult condition to treat. Some patients demonstrate recurrent stenosis after multiple endoscopic treatments and are either poor candidates for open procedures or do not desire open surgery. We sought to evaluate low-dose postoperative external beam radiotherapy (EBRT) as a novel therapy for patients with recurrent tracheal stenosis refractory to endoscopic therapies. METHOD: We performed a retrospective review of patients with recurrent tracheal stenosis who underwent EBRT in addition to endoscopic dilation. We compared the number of endoscopic procedures required in the 6 months before EBRT to the number required in the 6 months after EBRT. RESULTS: Six patients met criteria for inclusion in our study. The cause of stenosis was variable among the study population. In the 6 months leading up to EBRT, patients underwent an average 6.2 endoscopic procedures. This dropped to an average 1.9 procedures in the 6 months following EBRT (P < .001). CONCLUSION: Herein, we show that low-dose postoperative external beam radiotherapy (EBRT), a novel therapy for patients with recurrent tracheal stenosis refractory to endoscopic therapies, is effective in decreasing the frequency of endoscopic dilations. LEVEL OF EVIDENCE: 4.

Anatomy-based definition of point A utilizing three-dimensional volumetric imaging approach for high-dose-rate (HDR) intracavitary brachytherapy dose prescription when treating cervical cancer using limited resources.

This study was designed to determine whether volumetric imaging could identify consistent alternative prescription methods to Manchester/point A when prescribing radiation dose in the treatment of cervical cancer using HDR intracavitary brachy-therapy (ICBT). One hundred and twenty-five treatment plans of 25 patients treated for carcinoma of the cervix were reviewed retrospectively. Each patient received 5 fractions of HDR ICBT following initial cisplatin-based pelvic chemoradiation, and radiation dose was originally prescribed to point A (ICRU-38). The gross tumor volume (GTV) and high-risk clinical target volume (HR-CTV) were contoured in three dimensions on the CT datasets, and inferior-superior, anterior-posterior, and left-right dimensions HR-CTV were recorded along with multiple anatomic and skeletal dimensions for each patient. The least square-best fit regression lines were plotted between one half of the HR-CTV width and pelvic cavity dimension at femoral head level and at maximum cavity dimension. The points in both plots lie reasonably close to straight lines and are well defined by straight lines with slopes of 0.15 and 0.17; intercept on y-axes of -0.08 and -0.03, point A, at the same level as defined based on applicator coordinates, is defined using this correlation, which is a function of distance between femoral heads/dimensions of maximum pelvic cavity width. Both relations, defined by straight lines, provide an estimated location of point A, which provides adequate coverage to the HR-CTV compared to the point A defined based on applicator coordinates. The point A defined based on femoral head distance would, therefore, be a reasonable surrogate to use for dose prescription because of subjective variation of cavity width dimension. Simple surrogate anatomic/skeletal landmarks can be useful for prescribing radiation dose when treating cervical cancer using intracavitary brachytherapy in limited-resource settings. Our ongoing work will continue to refine these models.

Simple carotid-sparing intensity-modulated radiotherapy technique and preliminary experience for T1-2 glottic cancer.

PURPOSE: To investigate the dosimetry and feasibility of carotid-sparing intensity-modulated radiotherapy (IMRT) for early glottic cancer and to report preliminary clinical experience. METHODS AND MATERIALS: Digital Imaging and Communications in Medicine radiotherapy (DICOM-RT) datasets from 6 T1-2 conventionally treated glottic cancer patients were used to create both conventional IMRT plans. We developed a simplified IMRT planning algorithm with three fields and limited segments. Conventional and IMRT plans were compared using generalized equivalent uniform dose and dose-volume parameters for in-field carotid arteries, target volumes, and organs at risk. We have treated 11 patients with this simplified IMRT technique. RESULTS: Intensity-modulated radiotherapy consistently reduced radiation dose to the carotid arteries (p < 0.05) while maintaining the clinical target volume coverage. With conventional planning, median carotid V35, V50, and V63 were 100%, 100%, and 69.0%, respectively. With IMRT planning these decreased to 2%, 0%, and 0%, respectively (p < 0.01). Radiation planning and treatment times were similar for conventional radiotherapy and IMRT. Treatment results have been excellent thus far. CONCLUSIONS: Intensity-modulated radiotherapy significantly reduced unnecessary radiation dose to the carotid arteries compared with conventional lateral fields while maintaining clinical target volume coverage. Further experience and longer follow-up will be required to demonstrate outcomes for cancer control and carotid artery effects.

The effect of dental artifacts, contrast media, and experience on interobserver contouring variations in head and neck anatomy.

OBJECTIVES: To investigate interobserver variability in the delineation of head-and-neck (H&N) anatomic structures on CT images, including the effects of image artifacts and observer experience. METHODS: Nine observers (7 radiation oncologists, 1 surgeon, and 1 physician assistant) with varying levels of H&N delineation experience independently contoured H&N gross tumor volumes and critical structures on radiation therapy treatment planning CT images alongside reference diagnostic CT images for 4 patients with oropharynx cancer. Image artifacts from dental fillings partially obstructed 3 images. Differences in the structure volumes, center-of-volume positions, and boundary positions (1 SD) were measured. In-house software created three-dimensional overlap distributions, including all observers. The effects of dental artifacts and observer experience on contouring precision were investigated, and the need for contrast media was assessed. RESULTS: In the absence of artifacts, all 9 participants achieved reasonable precision (1 SD < or =3 mm all boundaries). The structures obscured by dental image artifacts had larger variations when measured by the 3 metrics (1 SD = 8 mm cranial/caudal boundary). Experience improved the interobserver consistency of contouring for structures obscured by artifacts (1 SD = 2 mm cranial/caudal boundary). CONCLUSIONS: Interobserver contouring variability for anatomic H&N structures, specifically oropharyngeal gross tumor volumes and parotid glands, was acceptable in the absence of artifacts. Dental artifacts increased the contouring variability, but experienced participants achieved reasonable precision even with artifacts present. With a staging contrast CT image as a reference, delineation on a noncontrast treatment planning CT image can achieve acceptable precision.

Control of growth of vestibular schwannomas with low-dose Gamma Knife surgery.

OBJECT: The treatment of solitary vestibular schwannomas by performing Gamma Knife surgery is well established. It has been reported that decreasing the surface dose reduces patient morbidity, especially facial weakness and numbness. The authors of this retrospective study examine patient data from a single center to determine if low-dose (< or = 14 Gy) GKS controls tumor growth as effectively as higher doses (> 14 Gy). METHODS: Based on the formula for ellipsoid volumes, the tumor volumes were calculated using measurements from MR images obtained at follow up in patients treated at the authors' center. Follow-up data were available in 159 patients with a mean age of 59.5 +/- 14.2 years at treatment. Fifty-six percent of the patients were women and 53.5% of the tumors were located on the right side of the brain. The mean tumor volume was 3.3 +/- 4.3 cm3 with 10% of the tumors having volumes larger than 8 cm3. After GKS, smaller tumors (> or = 40% decrease in volume) were observed in 44.8% of patients treated with a low dose and in 48.8% treated with a high dose. Enlarged tumors (> or = 40% increase in volume) were seen in 5.2% of the patients receiving a low dose and 2.3% of those receiving a high dose. These differences were not statistically significant. Patients who had been followed up for longer than 5 years after treatment had median residual volumes of only 28.2% of the starting volume in the low-dose group and 26% in the high-dose group. This difference was statistically not significant. CONCLUSIONS: No statistically significant differences were observed between tumors given low-dose radiation treatment and those given high-dose radiation treatment.

Importance of patient examination to clinical quality assurance in head and neck radiation oncology.

BACKGROUND: When quality assurance programs in clinical radiation oncology focus mainly on the technical aspects of treatment, they tend to underplay questions of therapeutic process and outcome. We determined the value of clinical peer review in radiation therapy for head and neck cancer that involved head and neck examination. METHODS: Data were collected prospectively on 134 consecutive patients with preliminary radiation therapy (RT) plans. Peer review was performed that included head and neck examination and imaging review to confirm target localization. RESULTS: Peer review led to changes in treatment plans for 66% of patients. Most changes were minor, but 11% of changes were major and thought to be of a magnitude that could potentially affect therapeutic outcome or normal tissue toxicity. Most changes involved target delineation based on physical findings CONCLUSIONS: Peer review of radiation target localization in RT plans led to changes that could potentially affect rates of cancer control or complication in about 10% of patients. We suggest that the accuracy of head and neck radiation oncology treatment plans might be increased by co-examination by another head and neck cancer specialist, typically a radiation oncologist or head and neck surgeon, to confirm RT target volumes.

Sinonasal malignancies with neuroendocrine differentiation: patterns of failure according to histologic phenotype.

BACKGROUND: Sinonasal neuroendocrine tumors are rare malignancies that are represented by a spectrum of histologies, including esthesioneuroblastoma (ENB), sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma (NEC), and small cell carcinoma (SmCC). The authors reviewed their institutional experience to determine whether sinonasal neuroendocrine tumors of different histologies have distinct clinical characteristics that warrant individualized treatment approaches. METHODS: The authors treated 72 adults with pathologically proven, nonmetastatic, primary sinonasal neuroendocrine tumors from 1982 to 2002. There were 31 patients with ENB, 16 patients with SNUC, 18 patients with NEC, and 7 patients with SmCC. Patients with ENB usually were treated with local therapy alone (surgery and/or radiotherapy); only 3 of 31 patients (9.7%) received treatment (radiation) to regional lymphatics, and only 5 of 31 patients (16.1%) received chemotherapy. In contrast, patients with non-ENB histologies usually received chemotherapy (10 of 16 patients with SNUC, 12 of 18 patients with NEC, and 5 of 7 patients with SmCC), and nonsurgical locoregional therapy was used more frequently (6 of 16 patients with SNUC, 4 of 18 patients with NEC, and 5 of 7 patients with SmCC). RESULTS: The median follow-up for surviving patients was 81.5 months (range, 6-266 months). The Kaplan-Meier estimate of overall survival at 5 years was 93.1% for patients with ENB, 62.5% for patients with SNUC, 64.2% for patients with NEC, and 28.6% for patients with SmCC (P = 0.0029; log-rank test). The local control rate at 5 years also was superior for patients who had ENB (96.2%) compared with patients who had SNUC (78.6%), NEC (72.6%), or SmCC (66.7%) (P = 0.04). The regional failure (RF) rate at 5 years was 8.7% for patients with ENB, 15.6% for patients with SNUC, 12.9% for patients with NEC, and 44.4% for patients with SmCC. Additional late events increased the RF rate for patients with ENB to 31.9% at 10 years. The distant metastasis rate at 5 years was 0.0% for patients with ENB, 25.4% for patients with SNUC, 14.1% for patients with NEC, and 75.0% for patients with SmCC. CONCLUSIONS: This spectrum of malignancies with neuroendocrine features shares a common site of origin within the head and neck, but their natural histories appear to diverge into two main groups: ENB and non-ENB. Patients with ENB had excellent local and distant control rates with local therapy alone. Given the higher rates of systemic failure for patients with SNUC, NEC, and SmCC, the authors favor the use of combined-modality therapy for these patients.

Quantification of volumetric and geometric changes occurring during fractionated radiotherapy for head-and-neck cancer using an integrated CT/linear accelerator system.

PURPOSE: Many patients receiving fractionated radiotherapy (RT) for head-and-neck cancer have marked anatomic changes during their course of treatment, including shrinking of the primary tumor or nodal masses, resolving postoperative changes/edema, and changes in overall body habitus/weight loss. We conducted a pilot study to quantify the magnitude of these anatomic changes with systematic CT imaging. METHODS AND MATERIALS: Fourteen assessable patients were enrolled in this pilot study. Eligible patients had to have a pathologic diagnosis of head-and-neck cancer, be treated with definitive external beam RT, and had have gross primary and/or cervical nodal disease measuring at least 4 cm in maximal diameter. All patients were treated using a new commercial integrated CT-linear accelerator system (EXaCT) that allows CT imaging at the daily RT sessions while the patient remains immobilized in the treatment position. CT scans were acquired three times weekly during the entire course of RT, and both gross tumor volumes (GTVs: primary tumor and involved lymph nodes) and normal tissues (parotid glands, spinal canal, mandible, and external contour) were manually contoured on every axial slice. Volumetric and positional changes relative to a central bony reference (the center of mass of the C2 vertebral body) were determined for each structure. RESULTS: Gross tumor volumes decreased throughout the course of fractionated RT, at a median rate of 0.2 cm(3) per treatment day (range, 0.01-1.95 cm(3)/d). In terms of the percentage of the initial volume, the GTVs decreased at a median rate of 1.8%/treatment day (range, 0.2-3.1%/d). On the last day of treatment, this corresponded to a median total relative loss of 69.5% of the initial GTV (range, 9.9-91.9%). In addition, the center of the mass of shrinking tumors changed position with time, indicating that GTV loss was frequently asymmetric. At treatment completion, the median center of the mass displacement (after corrections for daily setup variation) was 3.3 mm (range, 0-17.3 mm). Parotid glands also decreased in volume (median, 0.19 cm(3)/d range, 0.04-0.84 cm(3)/d), and generally shifted medially (median, 3.1 mm; range, 0-9.9 mm) with time. This medial displacement of the parotid glands correlated highly with the weight loss that occurred during treatment. CONCLUSION: Measurable anatomic changes occurred throughout fractionated external beam RT for head-and-neck cancers. These changes in the external contour, shape, and location of the target and critical structures appeared to be significant during the second half of treatment (after 3-4 weeks of treatment) and could have potential dosimetric impact when highly conformal treatment techniques are used. These data may, therefore, be useful in the development of an adaptive RT scheme (periodic adjustment of the conformal treatment plan) that takes into account such treatment-related anatomic changes. In theory, such a strategy would maximize the therapeutic ratio of RT.

New equations for matching a low neck field to oblique upper neck fields with collimator rotation in a 3-field monoisocentric setup for head-and-neck cancers.

With a monoisocentric 3-field technique for treating head-and-neck cancer, collimator rotation may be needed for the upper lateral fields to avoid cephalad-positioned shoulders or to avoid unnecessary arytenoid irradiation while maintaining more anterior coverage. For patients with unilateral lymphadenopathy, lateral oblique-opposed boost fields can be used to encompass the primary tumor and ipsilateral lymph nodes without junctioning through gross disease. When initial collimated lateral fields are also rotated with a gantry angle to produce oblique boost fields, however, the resulting matchline with a low anterior neck (LAN) boost field is no longer nondivergent. This can be corrected by manual adjustment of collimator and gantry angles for the LAN field using 3D treatment planning software. The goal of this study was to derive mathematical formulas to simplify this process. We used a transformation matrix to define formulas that could predict the appropriate modifications to the LAN boost field. Output from the formulas was (1) visually tested within 3D treatment planning software and (2) verified using a solid water head-and-neck phantom and radiographic film dosimetry to confirm that a nondivergent matchline was obtained in several clinical scenarios. When evaluated with 3D treatment planning software, the formulas accurately predicted the appropriate gantry and collimator angles of the LAN boost field for a variety of possible beam combinations. When evaluated with film dosimetry, the formulas were shown to accurately predict the appropriate gantry and collimator angles of the LAN boost field to within the +/- 2 mm/1 degrees tolerance specifications of the linear accelerator and acceptable for routine clinical use. The presented formulas are simple and geometrically precise. They predict the necessary manipulations of the LAN boost field to maintain a geometrically precise matchline, as verified by 3D treatment planning software, phantom dosimetry, and actual patient setups.

Concurrent chemotherapy and reduced-dose cranial spinal irradiation followed by conformal posterior fossa tumor bed boost for average-risk medulloblastoma: efficacy and patterns of failure.

PURPOSE: To review the efficacy and patterns of failure in average-risk medulloblastoma patients treated with concurrent chemotherapy and reduced-dose cranial spinal irradiation and a conformal tumor bed boost. METHODS AND MATERIALS: Thirty-three patients with average risk (defined as < or =1.5 cm(2) of residual tumor after resection, age >3 years, and no involvement of the cerebrospinal fluid or spine [M0]) medulloblastoma were diagnosed at our institution between January 1994 and December 2001. They were enrolled in an institutional pilot protocol consisting of concurrent chemotherapy (vincristine), reduced-dose cranial spinal irradiation (2340 cGy), a conformal primary tumor bed boost (3240 cGy), followed by eight cycles of chemotherapy (vincristine, cisplatin, and lomustine or cyclophosphamide). The median age at diagnosis of the 33 patients was 7 years (range, 3-21 years). The male/female patient ratio was 2.4:1. The median follow-up of the entire group was 37 months (range, 6-96 months), and the median follow-up of the survivors was 44 months (range, 10-96 months). RESULTS: The 5-year estimated disease-free survival rate, as determined by Kaplan-Meier plots, was 86% (+/-12.6%, 95% confidence interval). The 5-year estimated disease-free posterior fossa control and primary tumor bed control rates were both 94% (+/-8.2%, 95% confidence interval). The patterns of failure included 2 patients with distant central nervous system failure only, 1 patient who developed local primary tumor bed failure, posterior fossa failure, and diffuse leptomeningeal spread simultaneously, and 1 patient with failure in the high-dose, primary tumor bed field. No patient experienced isolated posterior fossa failure outside the high-dose boost region. CONCLUSION: The treatment of average-risk medulloblastoma with chemotherapy, reduced-dose cranial spinal irradiation, and a conformal tumor bed boost results in survival rates and local control rates comparable to those in contemporary studies. A reduction in the amount of posterior fossa treated to the high dose is possible. These results need to be corroborated in a large, cooperative group study.

Patterns of failure in relation to radiotherapy fields in supratentorial primitive neuroectodermal tumor.

PURPOSE: Supratentorial primitive neuroectodermal tumor (PNET) accounts for 2-3% of all pediatric brain tumors. We retrospectively reviewed all supratentorial PNET cases treated with radiotherapy (RT) at our institutions. METHODS AND MATERIALS: A total of 25 patients (17 males and 8 females, median age 9 years) were treated with RT between 1980 and 2001. The primary site location was the pineal region in 7 (28%), temporal lobe in 5 (20%), thalamus in 5 (20%), frontal lobe in 4 (16%), parietal lobe in 2 (8%), and suprasellar region in 2 (8%). Five patients (20%) had neuraxis dissemination (M+ disease) at initial diagnosis. The RT treatment volumes were craniospinal (CS) in 17 (68%), whole brain (WB) followed by a boost in 2 (8%), and primary site (PS) alone in 6 (24%). The median dose to the primary site was 54 Gy (range, 31-55.8 Gy). The median dose to patients receiving WB and spinal fields was 36 Gy (range, 23.4-39.6 Gy). Sixteen patients (64%) received chemotherapy; the most common type was the "8 in 1" chemotherapy regimen in 9 children. The median follow-up of surviving patients was 70 months (range, 34-251 months). RESULTS: The 5-year and 10-year progression-free survival rate was 36% and 27%, respectively, and the median time to progression was 22 months. The 5-year and 10-year progression-free survival rate was 47.1% and 47.1% for those receiving CSRT and 12.5% and 0% for those receiving WBRT or PSRT, respectively. The 5-year and 10-year progression-free survival rate for those with M0 disease was 40.0% and 30.0%, respectively; for those with M+ disease, the corresponding figures were 20.0% and 0%. On multivariate analysis, only M status (p = 0.01) and RT volume (p = 0.02) were statistically significant according to the Cox proportional hazards model. The primary site control rate at 5 and 10 years was 62%. Failure at nontreated neuraxis sites was a common cause of progression in patients receiving WBRT or PSRT, as seen in 6 (75%) of 8 cases. Of the 17 patients undergoing CSRT, 8 had no recurrence. Eight of the nine CSRT relapses had a leptomeningeal component. Four (80%) of 5 M+ children and 4 (33%) of 12 M0 children who underwent CSRT developed recurrence in the neuraxis (p = 0.1, Fisher's exact test). CONCLUSION: The craniospinal axis is the standard volume that needs to be treated in supratentorial PNET. Leptomeningeal dissemination was the main obstacle for cure even in patients receiving CSRT, regardless of M status.

Dose and volume reduction for normal lung using intensity-modulated radiotherapy for advanced-stage non-small-cell lung cancer.

PURPOSE: To investigate dosimetric improvements with respect to tumor-dose conformity and normal tissue sparing using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3D-CRT) for advanced-stage non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Forty-one patients with Stage III-IV and recurrent NSCLC who previously underwent 3D-CRT were included. IMRT plans were designed to deliver 63 Gy to 95% of the planning target volume using nine equidistant coplanar 6-MV beams. Inverse planning was performed to minimize the volumes of normal lung, heart, esophagus, and spinal cord irradiated above their tolerance doses. Dose distributions and dosimetric indexes for the tumors and critical structures in both plans were computed and compared. RESULTS: Using IMRT, the median absolute reduction in the percentage of lung volume irradiated to >10 and >20 Gy was 7% and 10%, respectively. This corresponded to a decrease of >2 Gy in the total lung mean dose and of 10% in the risk of radiation pneumonitis. The volumes of the heart and esophagus irradiated to >40-50 Gy and normal thoracic tissue volume irradiated to >10-40 Gy were reduced using the IMRT plans. A marginal increase occurred in the spinal cord maximal dose and lung volume >5 Gy in the IMRT plans, which could be have resulted from the significant increase in monitor units and thus leakage dose in IMRT. CONCLUSION: IMRT planning significantly improved target coverage and reduced the volume of normal lung irradiated above low doses. The spread of low doses to normal tissues can be controlled in IMRT with appropriately selected planning parameters. The dosimetric benefits of IMRT for advanced-stage non-small-cell lung cancer must be evaluated further in clinical trials.

Management of nonsinonasal neuroendocrine carcinomas of the head and neck.

BACKGROUND: Nonsinonasal neuroendocrine carcinomas (NSNEC) of the head and neck are rare and pose a diagnostic and management challenge. The authors undertook a retrospective study to gain insights into the spectrum of clinicopathologic characteristics, patterns of failure, and optimal management of patients with this disease. METHODS: The authors treated 23 adults with pathologically proven, nonmetastatic, primary NSNEC from 1984 to 2001. The majority (13 patients) had laryngeal origin with the following American Joint Committee on Cancer stage distribution: Stage I disease in 1 patient, Stage II disease in 2 patients, Stage III disease in 6 patients, and Stage IV disease in 14 patients. Nine patients underwent definitive surgery with or without postoperative radiation, and 14 patients received definitive radiotherapy. The median definitive radiation dose was 66 grays (Gy) (range, 44-72 Gy) using conventional fractionation. Fourteen patients received chemotherapy, with two to four cycles of induction platinum plus etoposide used most commonly. RESULTS: The median follow-up time for surviving patients was 40 months (range, 15-89 months). The actuarial 2-year and 5-year overall survival (OS) rates were 53% and 33%, respectively; and the disease-free survival (DFS) rates were 41% and 25%, respectively. Both the 2-year OS rate (68% vs. 30%; P = 0.002) and the 2-year DFS rate (55% vs. 17%; P = 0.004) were improved with chemotherapy compared with local therapy alone. Seventy-five percent of patients with measurable disease had complete clinical responses to induction chemotherapy. There was 100% complete clinical response of tumor after radiotherapy. The actuarial 2-year local failure rate was 23%. Chemotherapy did not reduce local failure (P = 0.91). There was no regional failure. The 2-year and 5-year distant metastasis rates were 54% and 71%, respectively. The 2-year rates of metastases without and with chemotherapy were 79% and 39%, respectively (P = 0.006). The 2-year and 5-year rates of intracranial metastases were 25% and 44%, respectively, and the 2-year and 5-year rates of isolated brain metastases were 21% and 41%, respectively. CONCLUSIONS: Based on these results, the authors' treatment strategy for patients with NSNEC is sequential chemotherapy and radiation. They recommend full-dose radiotherapy alone for patients with NSNEC who achieve a complete clinical response to induction chemotherapy. Newer chemotherapeutic regimens or additional adjuvant chemotherapy should be investigated for patients with NSNEC given the high rate of distant failure. Due to the very high rate of brain metastases among patients in the current study, the authors now consider incorporating prophylactic cranial irradiation into primary radiotherapy for individual patients who have complete clinical responses to induction chemotherapy.

Brain metastasis in children with sarcoma, neuroblastoma, and Wilms' tumor.

PURPOSE: To determine the incidence and prognosis of children who develop brain metastasis. MATERIALS AND METHODS: The medical and tumor registry records of 611 children treated at the University of Iowa Hospitals and Clinics between 1965 and 2000 for a sarcoma, neuroblastoma, or Wilms' tumor were reviewed. RESULTS: Thirty children (4.9%) were found to have brain metastasis. Brain metastasis occurred in 9 of 113 (8%) neuroblastoma, 7 of 104 (6.7%) rhabdomyosarcoma, 6 of 105 (5.7%) Ewing's sarcoma, 5 of 106 (4.7%) osteosarcoma, 2 of 83 (2.4%) nonrhabdomyosarcoma soft-tissue sarcoma, and 1 of 100 (1%) Wilms' tumor patients. There were 22 male and 8 female patients, with a median age of 14 years at the time of diagnosis of brain metastasis (range 8 months-20 years). Four patients were diagnosed at autopsy, whereas five had brain metastasis at initial diagnosis. For the 25 children who did not have brain metastasis at initial presentation, the median interval from initial diagnosis to development of brain metastasis was 5 months (range 1-43 months). Twenty-nine (97%) had concurrent or prior history of distant metastasis. Eighteen (60%) had solitary brain metastasis. Treatment for the 26 non-autopsy-diagnosed children included surgery (S), followed by postoperative radiotherapy (RT) and chemotherapy (CT) in 2, S and postoperative RT in 1, RT and CT in 16, S alone in 2, CT alone in 2, RT alone in 1, and no treatment in 2. Median survival was 4 months after diagnosis of brain metastasis, with a 1-year survival rate of 11.5%. On multivariate analysis, only the use of RT was found to positively influence freedom from neurologic progression (p = 0.005). CONCLUSION: Brain metastasis is uncommon in children with a diagnosis of sarcoma, neuroblastoma, or Wilms' tumor and is often accompanied by concurrent distant disease. Children treated with RT for brain metastasis had a better freedom from neurologic progression rate than those who did not receive radiotherapy.

Locoregional treatment for adult soft tissue sarcomas of the head and neck: an institutional review.

PURPOSE: The purpose of this study was to review treatment results for primary soft tissue sarcomas of the head and neck in order to determine prognostic factors. PATIENTS AND METHODS: From 1970 to 2000, 44 adult patients were diagnosed with a biopsy-proven, nonmetastatic primary soft tissue sarcoma in a head and neck subsite; were treated with curative intent; and had adequate follow-up and records for our review. Patients with extraosseous Ewing's sarcoma, Kaposi's sarcoma, rhabdomyosarcoma, dermatofibrosarcoma protuberans, and desmoid tumor were excluded. The most common tumor histologies included malignant fibrous histiocytoma (15 patients), angiosarcoma (nine patients), fibrosarcoma (six patients), and leiomyosarcoma (six patients). RESULTS: The median overall survival for all patients was 79 months. The actuarial 5-year local control for all patients was 55% and was highly correlated with the extent of surgical excision: 25% for subtotal resection/debulking, 65% for wide local excision, and 100% for radical excision. Local control at 5 years was 60% for patients treated with both surgery and radiotherapy, 54% for those treated with surgery alone, and 43% for those treated with radiotherapy alone. Adjuvant radiotherapy significantly improved the local control rates (from 25% to 54%) for patients with close (<2 mm) or positive surgical margins. Of 14 patients with locoregional failure in whom salvage was attempted, nine (64%) were rendered disease free. CONCLUSIONS: Multimodality therapy with both surgery and radiotherapy improves local control, particularly in patients with close or positive surgical margins. Aggressive attempts at salvage therapy for locoregional failures are warranted and frequently produce long-term disease control.