Purpose: Cone-beam computed tomography (CBCT) is a new image-guided radiation therapy (IGRT) technique for patient alignment in radiotherapy. The CBCT x-ray volume imaging system from Elekta allows for a variety of alignment methods. The aim of this study is to assess the accuracy of soft-tissue-based automatic alignment as compared with manual alignment using intraprostatic fiducials. Methods and Materials: All patients were treated on an Elekta Synergy S linear accelerator with kilovoltage CBCT. All alignments were performed using the x-ray volume imaging system and associated software. Automatic alignment with gray-value-based registration and manual alignment to fiducial markers were performed. Transitional corrections along each axis as well as 3-dimensional vectors were compared with evaluate the accuracy of gray-value-based registration compared with fiducials. Results: The distribution of the 3-dimensional vectors between gray-value and fiducial registrations demonstrated notable differences. The mean summed vector was 0.75 cm, with a standard deviation (SD) of 0.52 cm and range from 0.04 to 2.06 cm. There was minimal difference along the lateral direction, with a mean ± SD of −0.02 cm ± 0.13 cm. However, there were large discrepancies along the superior-inferior and anterior-posterior direction alignments, with mean ± SD values of −0.55 ± 0.48 cm and −0.31 ± 0.43 cm, respectively. Conclusions: CBCT with soft-tissue-based automatic corrections is not an accurate alignment compared with manual alignment to fiducial markers for prostate IGRT. We have concluded that a daily manual alignment to fiducials is one of the most reliable methods to maintain accuracy in prostate IGRT.

PURPOSE:To determine the residual setup errors of several image guidance scenarios, using cone-beam computed tomography (CBCT) in conventionally fractionated radiotherapy for lung tumors. METHODS:Thirteen lung cancer patients were treated with conventionally fractionated radiotherapy, using daily image guidance with CBCT, resulting in 389 CBCT scans which were registered to the planning scan using automated soft-tissue registration. Using the resulting daily alignment data, 4 imaging frequency scenarios were analyzed: (A) no imaging; (B) weekly imaging with a 3-mm threshold; (C) first 5 fractions imaged, then weekly imaging with a patient-specific threshold; and (D) imaging every other day. RESULTS:The systematic setup error (Sigma) was reduced with increasing frequency of imaging from 3.4 mm for no imaging to 1.0 mm for imaging every other day. Random setup error (sigma), however, varied little regardless of the frequency of imaging: 2.9, 3.0, 3.4, and 3.2 mm for scenarios A, B, C, and D, respectively. The setup margins required to account for the residual error of each imaging scenario were 1 to 1.6 cm for scenario A, 4 to 6 mm for scenarios B and C, and 4 to 5 mm for scenario D. As the residual error of daily CBCT was not included in this analysis, these margins compare with a margin of zero for daily CBCT. CONCLUSIONS:Daily image guidance is ideal as the setup margin can be reduced by about 5 mm versus a nondaily imaging scenario. However, if daily image guidance is not possible, there is little benefit in imaging more often than once a week.

Toxicity is considerable with the standard chemotherapy regimen of cisplatin 100mg/m2 every 3 weeks during radiotherapy (RT). We hypothesized that changing the chemotherapy regimen to a weekly dose of cisplatin 30 mg/m2 would decrease toxicity without compromising efficacy in patients with locally advanced squamous cell carcinoma (SCC) of the head and neck. The study population included 121 patients with AJCC Stage II (3%), Stage III (13%), or Stage IV (84%) SCC of the oropharynx (70%), hypopharynx (20%), or larynx (10%) treated from June 2000 to December 2006 at the University of Florida with altered fractionation RT and concomitant cisplatin given as a once-weekly infusion of 30mg/m2. The median RT dose was 72.4 Gy given with either twice-daily fractionation (45%) or the concomitant boost (55%) technique. IMRT was used in each patient treated with the concomitant boost technique. Our endpoints were: analysis of acute and late toxicities, local-regional control (LRC), disease-free survival (DFS), cause-specific survival (CSS), distant metastases (DM), and overall survival (OS). The minimum follow-up for all patients was 2 years. Seventy-nine percent of patients were able to complete at least 6 cycles of chemotherapy. Ninety-five percent of patients received RT to at least 72 Gy. The 5-year actuarial outcomes were: LRC, 79%; CSS, 76%; DM, 12%; and OS, 59%. Our toxicity rates (listed below) were lower than those reported for RTOG 9914 and 01291,2: G-tube rate at the end of treatment: 52% (vs. 83% and 64%)1,2 G-tube rate at 1 year: 3% (vs. 41% and 30%)1,2 CTC Grade 4 late complications: 6% (vs. 16% and 20%)1,2 CTC Grade 5 (fatal) toxicity: 2% (the same as seen in RTOG studies) 1,2 Our data suggests that, compared to more intensive regimens, weekly cisplatin at 30 mg/m2 decreases toxicity without compromising tumor control in patients who receive concomitant chemo-RT for SCC of the head and neck. These results need to be confirmed in prospective studies.

To report survival and control rates in patients with inoperable squamous cell carcinoma (SCCA) of the lung and to compare daily (QD) versus twice-daily (BID) radiotherapy treatment outcomes. Two hundred seventy-five patients with inoperable squamous cell carcinoma of the lung (stage I-IIIB) who received radiotherapy alone or combined with adjuvant chemotherapy at the University of Florida between 1963–2006 were retrospectively analyzed. All patients were treated with curative intent. Two hundred forty-nine patients received QD treatment and 26 patients were treated BID. The median dose of radiation for all patients was 65 Gy. Patients treated BID were more likely to have stage III or greater disease as compared to those treated QD (77% vs. 53%). Five-year local control was not significantly different for patients treated BID vs. QD (61% vs. 57%, p = 0.93). Five-year regional control was significantly improved with BID treatment vs. QD treatment (37% vs. 14%, p = 0.02). Five-year overall survival (OS) and cause-specific survival (CSS) were 19% vs. 8% and 38% vs. 21% for BID treatment and QD treatment, respectively (p = 0.35 for OS and p = 0.41 for CSS). Patients who received doses ≥65 Gy had improved OS and CSS compared with those who received doses <65 Gy (43% vs. 41%, p = 0.0001, and 10% vs. 7%, p = 0.003). Total dose (≥65 Gy vs. <65 Gy) did not affect median survival (17 vs. 14 months), local control (59% vs. 57%), or regional control (18% vs. 19%). However, 5-year metastasis-free survival was significantly improved for patients who received ≥65 Gy than for patients who received <65 Gy (73% vs. 59%, p = 0.003). Twice-daily radiotherapy for SCCA of the lung significantly improves regional control and trends toward improvements in CSS and OS. Although the trend is quite dramatic, the limited number of patients treated BID hampers the statistical significance of the data. This retrospective study confirms the ample data suggesting that altered fractionation and accelerated therapy may improve outcomes in SCCA of the lung. Additional prospective trials using hyperfractionation and accelerated dose to treat SCCA of the lung may reveal a more potent benefit. In this study, a dose of ≥65 Gy improved patients' CSS and OS. At the University of Florida we have begun treating unresectable stage III SCCA of the lung with doses of 69.6 Gy BID and concurrent chemotherapy.

Purpose/Objective(s)The literature for Stereotactic Body Radiotherapy (SBRT) in Lung Cancer is dominated by two very different approaches: the Indiana/RTOG method of 60 Gy in 3 fractions and the Japanese/JCOG method of 48 Gy in 4 fractions. Beyond dose, these two approaches use very different methods of defining targets and prescriptions. We compared the two methods in patients treated with thoracic SBRT at the University of Florida.Materials/Methods12 consecutive patients treated at the UF were used for comparison. Patients were immobilized with the Body Fit system and simulated using a 4D CT simulator. Treatment planning was done with Pinnacle 7.6c. The following volumes were created: GTV free breathing (GTVfb) was contoured using the free breathing CT scan. ITV was contoured on 10 individual CTs correlated to respiratory cycle (4DCT). CTV was defined at ITV + 7 mm to account for microscopic extension of tumor beyond the contoured volume, and was adjusted to match the ITV when it contacted the mediastinum or chest wall. The IU plans were prescribed 60 Gy in 3 fractions. The PTV = block edge = GTVfb + 0.5 cm laterally and 1 cm superiorly and inferiorly. The dose contour that contained the PTV was the prescription line. The IU plans were initially run without heterogeneity corrections, and then converted back to heterogeneity corrections after meeting the prescription requirements. The JP plans were prescribed 48 Gy in 4 fractions delivered to the isocenter (geometric center of the ITV). The plans were run with heterogeneity corrections and adjusted so that the ITV received 92–102% of the dose.ResultsThe mean GTVfb for the 12 tumors was 8.6 cm3, the mean ITV was 18.4 cm3 and the mean ratio of GTVfb/ITV was 2.3. The median minimum dose to the CTV (CTVmin) for the IU plans was 3442 cGy (range 627–5012 cGy), median mean dose (CTVmed) was 6609 cGy (5247–7385 cGy), median maximum dose (CTVmax) was 7857 cGy (6599–9575 cGy), and the median standard deviation (SD) of the CTV DVH was 783 cGy. For the JP plans the CTVmin was 4014 cGy (3519–4182 cGy), the CTVmed was 4634 cGy (4408–4984 cGy), CTVmax was 4853 cGy (4807–5421 cGy), and the median SD for the CTV DVH was 143 cGy (see table 1). The CTVmin for IU and JP were not statistically different (p = 0.07). The CTVmed and CTVmax were significantly higher on the IU plans (p < 0.0001).ConclusionsThe IU approach to lung SBRT produces significantly higher median and maximum doses to a 4D CTV as compared with the JP approach, but with much greater variability in dose delivered. The minimum dose delivered to the 4D CTV was higher in the JP plans, but not significantly so. These differences may help explain why two very different dose prescription methods yield similar results. Purpose/Objective(s)The literature for Stereotactic Body Radiotherapy (SBRT) in Lung Cancer is dominated by two very different approaches: the Indiana/RTOG method of 60 Gy in 3 fractions and the Japanese/JCOG method of 48 Gy in 4 fractions. Beyond dose, these two approaches use very different methods of defining targets and prescriptions. We compared the two methods in patients treated with thoracic SBRT at the University of Florida. The literature for Stereotactic Body Radiotherapy (SBRT) in Lung Cancer is dominated by two very different approaches: the Indiana/RTOG method of 60 Gy in 3 fractions and the Japanese/JCOG method of 48 Gy in 4 fractions. Beyond dose, these two approaches use very different methods of defining targets and prescriptions. We compared the two methods in patients treated with thoracic SBRT at the University of Florida. Materials/Methods12 consecutive patients treated at the UF were used for comparison. Patients were immobilized with the Body Fit system and simulated using a 4D CT simulator. Treatment planning was done with Pinnacle 7.6c. The following volumes were created: GTV free breathing (GTVfb) was contoured using the free breathing CT scan. ITV was contoured on 10 individual CTs correlated to respiratory cycle (4DCT). CTV was defined at ITV + 7 mm to account for microscopic extension of tumor beyond the contoured volume, and was adjusted to match the ITV when it contacted the mediastinum or chest wall. The IU plans were prescribed 60 Gy in 3 fractions. The PTV = block edge = GTVfb + 0.5 cm laterally and 1 cm superiorly and inferiorly. The dose contour that contained the PTV was the prescription line. The IU plans were initially run without heterogeneity corrections, and then converted back to heterogeneity corrections after meeting the prescription requirements. The JP plans were prescribed 48 Gy in 4 fractions delivered to the isocenter (geometric center of the ITV). The plans were run with heterogeneity corrections and adjusted so that the ITV received 92–102% of the dose. 12 consecutive patients treated at the UF were used for comparison. Patients were immobilized with the Body Fit system and simulated using a 4D CT simulator. Treatment planning was done with Pinnacle 7.6c. The following volumes were created: GTV free breathing (GTVfb) was contoured using the free breathing CT scan. ITV was contoured on 10 individual CTs correlated to respiratory cycle (4DCT). CTV was defined at ITV + 7 mm to account for microscopic extension of tumor beyond the contoured volume, and was adjusted to match the ITV when it contacted the mediastinum or chest wall. The IU plans were prescribed 60 Gy in 3 fractions. The PTV = block edge = GTVfb + 0.5 cm laterally and 1 cm superiorly and inferiorly. The dose contour that contained the PTV was the prescription line. The IU plans were initially run without heterogeneity corrections, and then converted back to heterogeneity corrections after meeting the prescription requirements. The JP plans were prescribed 48 Gy in 4 fractions delivered to the isocenter (geometric center of the ITV). The plans were run with heterogeneity corrections and adjusted so that the ITV received 92–102% of the dose. ResultsThe mean GTVfb for the 12 tumors was 8.6 cm3, the mean ITV was 18.4 cm3 and the mean ratio of GTVfb/ITV was 2.3. The median minimum dose to the CTV (CTVmin) for the IU plans was 3442 cGy (range 627–5012 cGy), median mean dose (CTVmed) was 6609 cGy (5247–7385 cGy), median maximum dose (CTVmax) was 7857 cGy (6599–9575 cGy), and the median standard deviation (SD) of the CTV DVH was 783 cGy. For the JP plans the CTVmin was 4014 cGy (3519–4182 cGy), the CTVmed was 4634 cGy (4408–4984 cGy), CTVmax was 4853 cGy (4807–5421 cGy), and the median SD for the CTV DVH was 143 cGy (see table 1). The CTVmin for IU and JP were not statistically different (p = 0.07). The CTVmed and CTVmax were significantly higher on the IU plans (p < 0.0001). The mean GTVfb for the 12 tumors was 8.6 cm3, the mean ITV was 18.4 cm3 and the mean ratio of GTVfb/ITV was 2.3. The median minimum dose to the CTV (CTVmin) for the IU plans was 3442 cGy (range 627–5012 cGy), median mean dose (CTVmed) was 6609 cGy (5247–7385 cGy), median maximum dose (CTVmax) was 7857 cGy (6599–9575 cGy), and the median standard deviation (SD) of the CTV DVH was 783 cGy. For the JP plans the CTVmin was 4014 cGy (3519–4182 cGy), the CTVmed was 4634 cGy (4408–4984 cGy), CTVmax was 4853 cGy (4807–5421 cGy), and the median SD for the CTV DVH was 143 cGy (see table 1). The CTVmin for IU and JP were not statistically different (p = 0.07). The CTVmed and CTVmax were significantly higher on the IU plans (p < 0.0001). ConclusionsThe IU approach to lung SBRT produces significantly higher median and maximum doses to a 4D CTV as compared with the JP approach, but with much greater variability in dose delivered. The minimum dose delivered to the 4D CTV was higher in the JP plans, but not significantly so. These differences may help explain why two very different dose prescription methods yield similar results. The IU approach to lung SBRT produces significantly higher median and maximum doses to a 4D CTV as compared with the JP approach, but with much greater variability in dose delivered. The minimum dose delivered to the 4D CTV was higher in the JP plans, but not significantly so. These differences may help explain why two very different dose prescription methods yield similar results.

Purpose: Delayed breast cellulitis (DBC) is characterized by the late onset of breast erythema, edema, tenderness, and warmth. This retrospective study analyzes the risk factors and clinical course of DBC.Methods and Materials: From 1985 through 2004, 580 sequential women with 601 stage T0-2N0-1 breast cancers underwent breast conserving therapy. Cases of DBC were identified according to accepted clinical criteria: diffuse breast erythema, edema, tenderness, and warmth occurring > 3 months after definitive surgery and > 3 weeks after radiotherapy. Potential risk factors analyzed included patient comorbidity, operative technique, acute complications, and details of adjunctive therapy. Response to treatment and long-term outcome were analyzed to characterize the natural course of this syndrome.Results: Of the 601 cases, 16%, 52%, and 32% were Stage 0, 1, and 11, respectively. The overall incidence of DBC was 8% (50/601). Obesity, ecchymoses, T stage, the presence and aspiration of a breast hematoma/ seroma, removal of > 5 axillary lymph nodes, and arm lymphedema were significantly associated with DBC. The median time to onset of DBC from the date of definitive surgery was 226 days. Ninety-two percent of DBC patients were empirically treated with antibiotics. Fourteen percent required more invasive intervention. Twenty-two percent had recurrent episodes of DBC. Ultimately, 2 patients (4%) underwent mastectomy for intractable breast pain related to DBC.Conclusion: Although multifactorial, we believe DBC is primarily related to a bacterial infection in the setting of impaired lymphatic drainage and may appear months after completion of radiotherapy. Invasive testing before a trial of antibiotics is generally not recommended. (c) 2006 Elsevier Inc.

PURPOSE:To define the optimal treatment of patients with squamous cell carcinoma (SCCA) of the anal margin. METHODS:Nineteen patients treated with curative intent by radiotherapy (RT) alone or combined with adjuvant chemotherapy (CTX) between 1979 and June 2000 were analyzed. The pertinent literature was reviewed and discussed as it related to our experience. RESULTS:Local control after RT or RT and CTX was observed in all 19 patients (100%). One T1 patient developed inguinal lymph node metastases and subsequently died secondary to regional and distant disease. This patient did not receive elective inguinal node RT; the lymph nodes of the other 18 patients in this analysis were irradiated. Four patients died of intercurrent disease at 25, 29, 37, and 113 months after RT, respectively. The remaining 14 patients were alive and disease-free from 52 to 143 months after treatment. No patient suffered a severe complication or required a diverting colostomy or an abdominoperineal resection (APR) after treatment. Review of the literature reveals that the probability of cure is similar after RT alone or combined with CTX compared with surgery. Therefore, the choice of treatment depends on the anticipated functional result. CONCLUSIONS:Patients with SCCA of the anal margin have a high likelihood of cure with sphincter preservation after RT or RT and CTX. Patients with well to moderately differentiated T1 tumors may undergo excision if it can be accomplished without compromising the sphincter. The remainder are treated with RT. Adjuvant CTX is indicated for those with T3-T4 tumors and/or involved regional nodes.