Defining internal target volume using positron emission tomography for radiation therapy planning of moving lung tumors.

Substantial disagreement exists over appropriate PET segmentation techniques for non-small cell lung cancer. Currently, no segmentation algorithm explicitly considers tumor motion in determining tumor borders. We developed an automatic PET segmentation model as a function of target volume, motion extent, and source-to-background ratio (the VMSBR model). The purpose of this work was to apply the VMSBR model and six other segmentation algorithms to a sample of lung tumors. PET and 4D CT were performed in the same imaging session for 23 patients (24 tumors) for radiation therapy planning. Internal target volumes (ITVs) were autosegmented on maximum intensity projection (MIP) of cine CT. ITVs were delineated on PET using the following methods: 15%, 35%, and 42% of maximum activity concentration, standardized uptake value (SUV) of 2.5 g/mL, 15% of mean activity concentration plus background, a linear function of mean SUV, and the VMSBR model. Predicted threshold values from each method were compared to measured optimal threshold values, and resulting volume magnitudes were compared to cine-CT-derived ITV. Correlation between predicted and measured threshold values ranged from slopes of 0.29 for the simplest single-threshold techniques to 0.90 for the VMSBR technique. R2 values ranged from 0.07 for the simplest single-threshold techniques to 0.86 for the VMSBR technique. The VMSBR segmentation technique that included volume, motion, and source-to-background ratio, produced accurate ITVs in patients when compared with cine-CT-derived ITV.

Capsular contracture of subcutaneous breast implant following hypofractionated stereotactic body radiotherapy for early stage lung cancer.

BACKGROUND: Development of capsular contracture around subcutaneously implanted breast prostheses, producing poor cosmetic outcome and pain, has been reported following standard fractionated external beam radiotherapy to whole implants for breast cancer. We report capsular contracture following partial implant irradiation from hypofractionated stereotactic body radiotherapy (SBRT) for lung cancer in a 64 year-old female with augmentation mammaplasty. METHODS: The patient had biopsy-proven, T1 non-small cell lung carcinoma, adjacent to the implant. She received 50 Gy in 4 fractions to 91% of planning target volume using a 7-field, 3D-conformal plan with 6 MV photons and daily CT-guided target localization. The implant received 9.3 Gy mean dose, 51.7 Gy maximum point dose, with V10 41%, V20 15% and V30 4%. RESULTS: At seven months, the patient reported left breast pain requiring narcotic analgesics and demonstrated modified Baker/Palmer grade 4 capsular contracture. Breast retraction assessment measurement increased from baseline 10.4 mm to 19.8 mm. CONCLUSIONS: This represents the first reported case of capsular contracture from partial breast implant radiation following SBRT for lung cancer. Further investigation to elucidate maximum tolerated dose of radiation given to breast implants in this setting is needed.

Daily alignment results of in-room computed tomography-guided stereotactic body radiation therapy for lung cancer.

PURPOSE: To determine the extent of interfractional setup errors and day-to-day organ motion errors by assessing daily bone alignment results and changes in soft tissue tumor position during hypofractionated, in-room computed tomography (CT)-guided stereotactic body radiation therapy (SBRT) of lung cancer. METHODS AND MATERIALS: Daily alignment results during SBRT were analyzed for 117 tumors in 112 patients. Patients received 40-50 Gy of SBRT in four to five fractions using an integrated CT-LINAC system. The free-breathing CT scans acquired during treatment setup were retrospectively realigned to match with each of the bony references and the gross tumor volume (GTV) defined on the reference CT by rigid-body registration, and the daily deviations were calculated. RESULTS: The mean magnitude (± SD) three-dimensional shift from the initial skin marks to the final bone-aligned positions was 9.4 ± 5.7 mm. The mean daily GTV deviation from the bone position was 0.1 ± 3.8 mm in the anterior-posterior direction, -0.01 ± 4.2 mm in the superior-inferior direction, and 0.2 ± 2.5 mm in the lateral direction. A clinically noteworthy trend (net change >5 mm in any direction) in GTV position relative to the bone was observed in 23 cases (20%). CONCLUSIONS: Soft tissue target position can change significantly beyond the motion envelope defined in the original internal target volume in four-dimensional CT-based treatment planning for SBRT of lung cancer. Additional margin should be considered for adequate coverage of interfractional changes.

Target definition of moving lung tumors in positron emission tomography: correlation of optimal activity concentration thresholds with object size, motion extent, and source-to-background ratio.

PURPOSE: Hardware integration of fluorodeoxyglucose positron emission tomography (PET) with computed tomography (CT) in combined PET/CT scanners has provided radiation oncologists and physicists with new possibilities for 3-D treatment simulation. The use of PET/CT simulation for target delineation of lung cancer is becoming popular and many studies concerning automatic segmentation of PET images have been performed. Several of these studies consider size and source-to-background (SBR) in their segmentation methods but neglect respiratory motion. The purpose of the current study was to develop a functional relationship between optimal activity concentration threshold, tumor volume, motion extent, and SBR using multiple regression techniques by performing an extensive series of phantom scans simulating tumors of varying sizes, SBR, and motion amplitudes. Segmented volumes on PET were compared with the "motion envelope" of the moving sphere defined on cine CT. METHODS: A NEMA IEC thorax phantom containing six spheres (inner diameters ranging from 10 to 37 mm) was placed on a motion platform and moved sinusoidally at 0-30 mm (at 5 mm intervals) and six different SBRs (ranging from 5:1 to 50:1), producing 252 combinations of experimental parameters. PET images were acquired for 18 min and split into three 6 min acquisitions for reproducibility. The spheres (blurred on PET images due to motion) were segmented at 1% of maximum activity concentration intervals. The optimal threshold was determined by comparing deviations between the threshold volume surfaces with a reference volume surface defined on cine CT. Optimal activity concentration thresholds were normalized to background and multiple regression was used to determine the relationship between optimal threshold, volume, motion, and SBR. Standardized regression coefficients were used to assess the relative influence of each variable. The segmentation model was applied to three lung cancer patients and segmented regions of interest were compared with those segmented on cine CT. RESULTS: The resulting model and coefficients provided a functional form that fit the phantom data with an adjusted R2 = 0.96. The most significant contributor to threshold level was SBR. Surfaces of PET-segmented volumes of three lung cancer patients were within 2 mm of the reference CT volumes on average. CONCLUSIONS: The authors successfully developed an expression for optimal activity concentration threshold as a function of object volume, motion, and SBR.

Is sex associated with the outcome of patients treated with radiation for nonsmall cell lung cancer?

BACKGROUND: Lung cancer is the leading cause of cancer death for both men and women, but the disease course differs between the sexes. To the authors' knowledge, sex-based differences in outcomes among the population of nonsmall cell lung cancer (NSCLC) patients receiving radiation have not been well defined. METHODS: Data for 831 patients (319 women and 512 men) with stage I to III NSCLC and treated with > or =45 Gray of radiation between March 1985 and November 2003 were retrospectively analyzed (grading determined according to the 1997 American Joint Committee on Cancer grading system). RESULTS: Women were more likely to have earlier stage disease, to have smoked <50 pack-years, and to have adenocarcinoma or large-cell carcinoma (all P < or = .001). For each stage, treatment did not differ between women and men. Five-year survival rates were significantly better for women than for men: overall survival (OS), 28.6% versus 16.1% (P < .001); disease-free survival, 31.2% versus 20.1% (P = .02); and distant metastasis-free survival, 48.8% versus 37.6% (P < .02). Among patients with medically inoperable stage I NSCLC, women had improved 5-year OS compared with men (30.0% vs 13.1%; P = .004). On multivariate analysis, male sex, weight loss, age > or =65 years, and stage III disease were found to be associated with poorer OS (all P < 0.02). CONCLUSIONS: Although women are more likely to have earlier stage disease, among patients with medically inoperable stage I NSCLC, women still have a better OS. Along with known prognostic factors, including age, weight loss, and stage, sex remained significant on multivariate analysis of OS, suggesting that sex is a determinant of outcome in NSCLC patients receiving radiation.

Stereotactic body radiation therapy in centrally and superiorly located stage I or isolated recurrent non-small-cell lung cancer.

PURPOSE: To evaluate the efficacy and adverse effects of image-guided stereotactic body radiation therapy (SBRT) in centrally/superiorly located non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: We delivered SBRT to 27 patients, 13 with Stage I and 14 with isolated recurrent NSCLC. A central/superior location was defined as being within 2 cm of the bronchial tree, major vessels, esophagus, heart, trachea, pericardium, brachial plexus, or vertebral body, but 1 cm away from the spinal canal. All patients underwent four-dimensional computed tomography-based planning, and daily computed tomography-on-rail guided SBRT. The prescribed dose of 40 Gy (n = 7) to the planning target volume was escalated to 50 Gy (n = 20) in 4 consecutive days. RESULTS: With a median follow-up of 17 months (range, 6-40 months), the crude local control at the treated site was 100% using 50 Gy. However, 3 of 7 patients had local recurrences when treated using 40 Gy. Of the patients with Stage I disease, 1 (7.7%) and 2 (15.4%) developed mediastinal lymph node metastasis and distant metastases, respectively. Of the patients with recurrent disease, 3 (21.4%) and 5 (35.7%) developed mediastinal lymph node metastasis and distant metastasis, respectively. Four patients (28.6%) with recurrent disease but none with Stage I disease developed Grade 2 pneumonitis. Three patients (11.1%) developed Grade 2-3 dermatitis and chest wall pain. One patient developed brachial plexus neuropathy. No esophagitis was noted in any patient. CONCLUSIONS: Image-guided SBRT using 50 Gy delivered in four fractions is feasible and resulted in excellent local control.

Squamous cell carcinoma of the buccal mucosa: a retrospective analysis of 22 cases.

We examined our institution's experience with 22 cases of previously untreated buccal squamous cell carcinoma via a retrospective chart review. Eleven of these patients had been treated with a combination of surgical excision and postoperative radiation therapy, 8 patients with surgical excision alone, and 3 patients with radiation therapy alone. The overall 3-year locoregional recurrence rate was 32% (n = 7). The 3-year survival rates were 82% after surgery plus radiation (9 of 11 patients), 63% after surgery alone (5 of 8), and 33% after radiation alone (1 of 3). Three-year T-category-specific survival rates were 100% for category T1 tumors (3 of 3 patients), 73% for T2 (8 of 11), 50% for T3 (3 of 6), and 50% for T4 (1 of 2). Although the small size of our study precluded any statistically significant conclusions, we believe that locoregional control and survival rates may be greater with surgical excision plus postoperative radiation than with treatment with either modality alone.

Comparison of rigid and adaptive methods of propagating gross tumor volume through respiratory phases of four-dimensional computed tomography image data set.

PURPOSE: To compare three different methods of propagating the gross tumor volume (GTV) through the respiratory phases that constitute a four-dimensional computed tomography image data set. METHODS AND MATERIALS: Four-dimensional computed tomography data sets of 20 patients who had undergone definitive hypofractionated radiotherapy to the lung were acquired. The GTV regions of interest (ROIs) were manually delineated on each phase of the four-dimensional computed tomography data set. The ROI from the end-expiration phase was propagated to the remaining nine phases of respiration using the following three techniques: (1) rigid-image registration using in-house software, (2) rigid image registration using research software from a commercial radiotherapy planning system vendor, and (3) rigid-image registration followed by deformable adaptation originally intended for organ-at-risk delineation using the same software. The internal GTVs generated from the various propagation methods were compared with the manual internal GTV using the normalized Dice similarity coefficient (DSC) index. RESULTS: The normalized DSC index of 1.01 +/- 0.06 (SD) for rigid propagation using the in-house software program was identical to the normalized DSC index of 1.01 +/- 0.06 for rigid propagation achieved with the vendor's research software. Adaptive propagation yielded poorer results, with a normalized DSC index of 0.89 +/- 0.10 (paired t test, p <0.001). CONCLUSION: Propagation of the GTV ROIs through the respiratory phases using rigid- body registration is an acceptable method within a 1-mm margin of uncertainty. The adaptive organ-at-risk propagation method was not applicable to propagating GTV ROIs, resulting in an unacceptable reduction of the volume and distortion of the ROIs.

Patterns of failure after combined-modality approaches incorporating radiotherapy for sinonasal undifferentiated carcinoma of the head and neck.

PURPOSE: To report the clinical outcome of patients treated with combined-modality approaches for sinonasal undifferentiated carcinoma (SNUC) of the head and neck. METHODS AND MATERIALS: The records of 21 patients with SNUC treated with curative intent at the University of California, San Francisco between 1990 and 2004 were analyzed. Patient age ranged from 33 to 71 years (median, 47 years). Primary tumor sites included the nasal cavity (11 patients), maxillary sinus (5 patients), and ethmoid sinus (5 patients). All patients had T3 (4 patients) or T4 (17 patients) tumors. Local-regional treatment included surgery followed by postoperative radiotherapy (PORT) with or without adjuvant chemotherapy for 17 patients; neoadjuvant chemoradiotherapy followed by surgery for 2 patients; and definitive chemoradiotherapy for 2 patients. Median follow-up among surviving patients was 58 months (range, 12-70 months). RESULTS: The 2- and 5-year estimates of local control were 60% and 56%, respectively. There was no difference in local control according to initial treatment approach, but among the 19 patients who underwent surgery the 5-year local control rate was 74% for those with gross tumor resection, compared with 24% for those with subtotal tumor resection (p = 0.001). The 5-year rates of overall and distant metastasis-free survival were 43% and 64%, respectively. Late complications included cataracts (2 patients), lacrimal stenosis (1 patient), and sino-cutaneous fistula (1 patient). CONCLUSION: The suboptimal outcomes suggest a need for more effective therapies. Gross total resection should be the goal of all treatments whenever possible.

Recurrent salivary gland carcinomas treated by surgery with or without intraoperative radiation therapy.

BACKGROUND: The optimal treatment for patients with locally recurrent carcinomas of the salivary glands is unclear. METHODS: Ninety-nine patients underwent salvage surgery for locally recurrent salivary gland carcinomas. Eighty-one (82%) had previously received radiation. Thirty-seven patients (37%) received intraoperative radiation therapy (IORT) to a median dose of 15 Gy (range, 12-18 Gy) at the time of salvage. RESULTS: The 1-, 3-, and 5-year estimates of local control after salvage surgery were 88%, 75%, and 69%, respectively. A Cox proportional hazard model identified positive margins (0.01) and the omission of IORT (p = .001) as independent predictors of local failure. The 5-year overall survival was 34%. Distant metastasis was the most common site of subsequent failure, occurring in 42% of patients. CONCLUSIONS: IORT significantly improves disease control for patients with locally recurrent carcinomas of the salivary glands. The high rate of distant metastasis emphasizes the need for effective systemic therapies.

Determination of respiratory motion for distal esophagus cancer using four-dimensional computed tomography.

PURPOSE: To investigate the motion characteristics of distal esophagus cancer primary tumors using four-dimensional computed tomography (4D CT). METHODS AND MATERIALS: Thirty-one consecutive patients treated for esophagus cancer who received respiratory-gated 4D CT imaging for treatment planning were selected. Deformable image registration was used to map the full expiratory motion gross tumor volume (GTV) to the full-inspiratory CT image, allowing quantitative assessment of each voxel's displacement. These displacements were correlated with patient tumor and respiratory characteristics. RESULTS: The mean (SE) tidal volume was 608 (73) mL. The mean GTV volume was 64.3 (10.7) mL on expiration and 64.1 (10.7) mL on inspiration (no significant difference). The mean tumor motion in the x-direction was 0.13 (0.006) cm (average of absolute values), in the y-direction 0.23 (0.01) cm (anteriorly), and in the z-direction 0.71 (0.02) cm (inferiorly). Tumor motion correlated with tidal volume. Comparison of tumor motion above vs. below the diaphragm was significant for the average net displacement (p = 0.014), motion below the diaphragm was greater than above. From the cumulative distribution 95% of the tumors moved less than 0.80 cm radially and 1.75 cm inferiorly. CONCLUSIONS: Primary esophagus tumor motion was evaluated with 4D CT. According to the results of this study, when 4D CT is not available, a radial margin of 0.8 cm and axial margin of +/-1.8 cm would provide tumor motion coverage for 95% of the cases in our study population.

Intrathoracic patterns of failure for non-small-cell lung cancer with positron-emission tomography/computed tomography-defined target delineation.

PURPOSE: Dosimetric studies suggested several advantages to defining the radiotherapy target by using positron-emission tomography (PET)/computed tomography (CT) compared with CT alone. We investigated patterns of treatment failure in patients treated to a PET-defined radiotherapy target and evaluated the effect of standardized uptake value (SUV) on recurrence after radiotherapy. METHODS AND MATERIALS: Thirty-five patients with non-small-cell lung cancer who underwent PET/CT simulation for definitive radiotherapy were included. The PET/CT scans were obtained with patients in the treatment position with custom immobilization for use in radiation treatment planning. Nine to 11 regions of interest (ROIs) were identified for each patient, including the primary tumor and regional nodes. Maximum SUV, volume, and mean dose received were recorded for each ROI, and follow-up scans were used to evaluate for recurrence in each ROI. RESULTS: We identified 353 ROIs from 35 patients; 5.7% of patients developed isolated out-of-field recurrences. Recursive partitioning analysis was used to divide ROIs into low, intermediate, and high risk by using volume and SUV. All low-risk ROIs with volumes less than 1.2 cm3 were recurrence free compared with 73% of intermediate-risk ROIs (volume >or=1.2 cm3; SUV 13.8). CONCLUSION: Limiting the target volume to predominantly PET-positive disease resulted in a low rate of isolated out-of-field recurrences. The SUV and volume were predictors of recurrence. Recursive partitioning analysis identified SUVs greater than 13.8 as the best identifier of ROIs at the greatest risk of recurrence; control rates for this subgroup did not show a dose-response relationship within the range of doses administered.

Evaluation of respiratory-induced target motion for esophageal tumors at the gastroesophageal junction.

PURPOSE: To quantify the internal motion margin requirements for radiotherapy of tumors near the gastroesophageal junction (GEJ). METHODS AND MATERIALS: Four-dimensional computed tomography (4DCT) scans were obtained for 25 patients with primary tumors located near the GEJ. The gross tumor volume (GTV) was manually contoured on the exhale-phase image from the 4DCT image set. A deformable image registration method was used to automatically propagate the contours to other phases of the 4DCT images. To quantify target motion, we measured the displacement of the GTV centroid and the variations in the target boundary and volume. Internal margins were calculated in the lateral (RL), anterior-posterior (AP), and superior-inferior (SI) directions. RESULTS: The mean+/-standard deviation peak-to-peak GTV centroid motion was 0.39+/-0.27cm (range, 0.04-1.09cm) in the RL, 0.38+/-0.23cm (range, 0.10-0.94cm) in the AP, and 0.87+/-0.47cm (range, 0.43-2.63cm) in the SI directions, respectively. On average, the internal target volume was 72% (range, 9-172%) larger than the GTV defined on a single-phase CT image. Variations in tumor boundaries due to tissue motion and deformation suggested asymmetric margins: 1.0cm left [toward the stomach], 0.8cm right, 1.1cm anterior, 0.6cm posterior, 1.0cm superior (toward the distal esophagus), and 1.6cm inferior (toward the stomach). CONCLUSION: Because tumors near the GEJ are subject to a marked but asymmetric amount of respiratory-induced intrafractional tumor motion, the use of asymmetric internal margins may be beneficial.

Carcinomas of the paranasal sinuses and nasal cavity treated with radiotherapy at a single institution over five decades: are we making improvement?

PURPOSE: To compare clinical outcomes of patients with carcinomas of the paranasal sinuses and nasal cavity according to decade of radiation treatment. METHODS AND MATERIALS: Between 1960 and 2005, 127 patients with sinonasal carcinoma underwent radiotherapy with planning and delivery techniques available at the time of treatment. Fifty-nine patients were treated by conventional radiotherapy; 45 patients by three-dimensional conformal radiotherapy; and 23 patients by intensity-modulated radiotherapy. Eighty-two patients (65%) were treated with radiotherapy after gross total tumor resection. Nineteen patients (15%) received chemotherapy. The most common histology was squamous cell carcinoma (83 patients). RESULTS: The 5-year estimates of overall survival, local control, and disease-free survival for the entire patient population were 52%, 62%, and 54%, respectively. There were no significant differences in any of these endpoints with respect to decade of treatment or radiotherapy technique (p > 0.05, for all). The 5-year overall survival rate for patients treated in the 1960s, 1970s, 1980s, 1990s, and 2000s was 46%, 56%, 51%, 53%, and 49%, respectively (p = 0.23). The observed incidence of severe (Grade 3 or 4) late toxicity was 53%, 45%, 39%, 28%, and 16% among patients treated in the 1960s, 1970s, 1980s, 1990s, and 2000s, respectively (p = 0.01). CONCLUSION: Although we did not detect improvements in disease control or overall survival for patients treated over time, the incidence of complications has significantly declined, thereby resulting in an improved therapeutic ratio for patients with carcinomas of the paranasal sinuses and nasal cavity.

Patterns of nodal relapse after surgery and postoperative radiation therapy for carcinomas of the major and minor salivary glands: what is the role of elective neck irradiation?

PURPOSE: To evaluate the incidence of nodal relapses from carcinomas of the salivary glands among patients with clinically negative necks in an attempt to determine the potential utility of elective neck irradiation (ENI). METHODS AND MATERIALS: Between 1960 and 2004, 251 patients with clinically N0 carcinomas of the salivary glands were treated with surgery and postoperative radiation therapy. None of the patients had undergone previous neck dissection. Histology was: adenoid cystic (84 patients), mucoepidermoid (60 patients), adenocarcinoma (58 patients), acinic cell (21 patients), undifferentiated (11 patients), carcinoma ex pleomorphic adenoma (7 patients), squamous cell (7 patients), and salivary duct carcinoma (3 patients); 131 patients (52%) had ENI. Median follow-up was 62 months (range, 3-267 months). RESULTS: The 5- and 10-year actuarial estimates of nodal relapse were 11% and 13%, respectively. The 10-year actuarial rates of nodal failure were 7%, 5%, 12%, and 16%, for patients with T1, T2, T3, and T4 disease, respectively (p = 0.11). The use of ENI reduced the 10-year nodal failure rate from 26% to 0% (p = 0.0001). The highest crude rates of nodal relapse among those treated without ENI were found in patients with squamous cell carcinoma (67%), undifferentiated carcinoma (50%), adenocarcinoma (34%), and mucoepidermoid carcinoma (29%). There were no nodal failures observed among patients with adenoid cystic or acinic cell histology. CONCLUSION: ENI effectively prevents nodal relapses and should be used for select patients at high risk for regional failure.

Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: implications for adjuvant therapy.

PURPOSE: To determine factors predictive of local-regional recurrence (LRR) after surgery alone for carcinomas of the major salivary glands in an attempt to evaluate the potential role of postoperative radiation therapy. METHODS AND MATERIALS: Between 1960 and 2004, 207 patients with carcinomas of the major salivary glands were treated with definitive surgery without postoperative radiation therapy. Histology was: 67 mucoepidermoid (32%), 50 adenoid cystic (24%), 34 acinic cell (16%), 23 malignant mixed (11%), 16 adenocarcinoma (8%), 6 oncocytic (3%), 6 myoepithelial (3%), and 5 other (2%). Distribution of pathologic T-stage was: 54 T1 (26%), 83 T2 (40%), 46 T3 (22%), and 24 T4 (12%). Sixty patients (29%) had microscopically positive margins. Median follow-up was 6.1 years (range, 0.5-18.7 years). RESULTS: The 5-year and 10-year estimates of local-regional control were 86% and 74%, respectively. A Cox proportional hazard model identified pathologic lymph node metastasis (hazard ratio [HR], 4.8; p = 0.001), high histologic grade (HR, 4.2; p = 0.003), positive margins (HR, 2.6; p = 0.03), and T3-4 disease (HR, 2.0; p = 0.04) as independent predictors of LRR. The presence of any one of these factors was associated with 10-year local-regional control rates of 37% to 63%. CONCLUSION: Lymph node metastasis, high tumor grade, positive margins, and T3-4 stage predict for significant rates of LRR after surgery for carcinomas of the major salivary glands. Postoperative radiation therapy should be considered for patients with these disease characteristics.

The role of postoperative radiation therapy in carcinoma ex pleomorphic adenoma of the parotid gland.

PURPOSE: To evaluate the impact of postoperative radiation therapy on the clinical course of patients with carcinoma ex pleomorphic adenoma of the parotid gland. METHODS AND MATERIALS: Between 1960 and 2004, 63 patients were treated with definitive surgery for carcinoma ex pleomorphic adenoma of the parotid gland. Forty patients (63%) received postoperative radiation therapy to a median dose of 60 Gy (range, 45-71 Gy). Adenocarcinoma (29 patients), salivary duct carcinoma (16 patients), and adenoid cystic carcinoma (9 patients) were the most common malignant subtypes. Pathologic T -stage was: 16% T1, 33% T2, 32% T3, and 19% T4. Twenty-one patients (33%) had microscopically positive margins and 39 (62%) had perineural invasion. Median follow-up was 50 months (range, 2-96 months). RESULTS: The use of postoperative therapy significantly improved 5-year local control from 49% to 75% (p = 0.005) and was associated with an improvement in survival among patients without evidence of cervical lymph node metastasis (p = 0.01). A Cox proportional hazard model identified pathologic involvement of cervical lymph nodes as an independent predictor of overall survival. Overall survival was 16% for patients with pathologic N-positive disease compared with 67% for those whose lymph node status was negative or unknown (p = 0.001). CONCLUSION: Surgery followed by postoperative radiation should be considered the standard of care for patients with carcinoma ex pleomorphic adenoma.

Intraoperative radiation therapy for recurrent head-and-neck cancer: the UCSF experience.

PURPOSE: To review a single-institutional experience with the use of intraoperative radiation therapy (IORT) for recurrent head-and-neck cancer. METHODS AND MATERIALS: Between 1991 and 2004, 137 patients were treated with gross total resection and IORT for recurrence or persistence of locoregional cancer of the head and neck. One hundred and thirteen patients (83%) had previously received external beam radiation as a component of definitive therapy. Ninety-four patients (69%) had squamous cell histology. Final surgical margins were microscopically positive in 56 patients (41%). IORT was delivered using either a modified linear accelerator or a mobile electron unit and was administered as a single fraction to a median dose of 15 Gy (range, 10-18 Gy). Median follow-up among surviving patients was 41 months (range, 3-122 months). RESULTS: The 1-year, 2-year, and 3-year estimates of in-field control after salvage surgery and IORT were 70%, 64%, and 61%, respectively. Positive margins at the time of IORT predicted for in-field failure (p = 0.001). The 3-year rates of locoregional control, distant metastasis-free survival, and overall survival were 51%, 46%, and 36%, respectively. There were no perioperative fatalities. Complications included wound infection (4 patients), orocutaneous fistula (2 patients), flap necrosis (1 patient), trismus (1 patient), and neuropathy (1 patient). CONCLUSIONS: Intraoperative RT results in effective disease control with acceptable toxicity and should be considered for selected patients with recurrent or persistent cancers of the head and neck.

Intensity-modulated radiation therapy for malignancies of the nasal cavity and paranasal sinuses.

PURPOSE: To report the clinical outcome of patients treated with intensity-modulated radiation therapy (IMRT) for malignancies of the nasal cavity and paranasal sinuses. METHODS AND MATERIALS: Between 1998 and 2004, 36 patients with malignancies of the sinonasal region were treated with IMRT. Thirty-two patients (89%) were treated in the postoperative setting after gross total resection. Treatment plans were designed to provide a dose of 70 Gy to 95% or more of the gross tumor volume (GTV) and 60 Gy to 95% or more of the clinical tumor volume (CTV) while sparing neighboring critical structures including the optic chiasm, optic nerves, eyes, and brainstem. The primary sites were: 13 ethmoid sinus, 10 maxillary sinus, 7 nasal cavity, and 6 other. Histology was: 12 squamous cell, 7 esthesioneuroblastoma, 5 adenoid cystic, 5 undifferentiated, 5 adenocarcinoma, and 2 other. Median follow-up was 51 months among surviving patients (range, 9-82 months). RESULTS: The 2-year and 5-year estimates of local control were 62% and 58%, respectively. One patient developed isolated distant metastasis, and none developed isolated regional failure. The 5-year rates of disease-free and overall survival were 55% and 45%, respectively. The incidence of ocular toxicity was minimal with no patients reporting decreased vision. Late complications included xerophthalmia (1 patient), lacrimal stenosis (1 patient), and cataract (1 patient). CONCLUSION: Although IMRT for malignancies of the sinonasal region does not appear to lead to significant improvements in disease control, the low incidence of complications is encouraging.

Recurrent pleomorphic adenoma of the parotid gland: long-term outcome of patients treated with radiation therapy.

PURPOSE: To evaluate the role of radiation therapy in the management of recurrent pleomorphic adenoma of the parotid gland. METHODS AND MATERIALS: Between 1960 and 2004, 34 patients were treated with postoperative radiation therapy for recurrent pleomorphic adenoma of the parotid gland to a median dose of 5000 cGy (range, 4,500-6,000 cGy). Median age was 48 years (range, 24-72 years). Gross total resection at the time of surgery before radiation was achieved in 30 patients (88%), and histologic analysis demonstrated multifocal disease in 16 patients (47%). Radiation was delivered for a first, second, third, fourth, fifth, and sixth local recurrence in 24%, 21%, 24%, 24%, 6%, and 3% of patients, respectively. RESULTS: With a median follow-up of 17.4 years (range, 2.3-28.9 years), 2 patients had local recurrences at a median of 3.4 years after completion of radiation. The 20-year actuarial local control rate was 94%. One patient developed a second malignancy at approximately 14 years after completion of therapy. CONCLUSION: The use of postoperative radiation therapy leads to excellent long-term local control for the treatment of recurrent pleomorphic adenoma with acceptable late toxicity. Although the incidence of second malignancy was low in this population, continued follow-up is warranted.