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At least 325 records · Page 18

Rectal Motion in Patients Receiving Preoperative Radiotherapy for Carcinoma of the Rectum

Purpose: To assess the movement of rectum, mesorectum, and rectal primary during a course of preoperative chemoradiotherapy. Methods and Materials: Seventeen patients with Stage II or III rectal cancer had a planning CT scan with rectal contrast before commencement of preoperative chemoradiation. The scan was repeated during Weeks 1, 3, and 5 of chemoradiation. The rectal primary (gross tumor volume), rectum, mesorectum, and bladder were contoured on all four scans. An in-house biomechanical model-based deformable image registration technique, Morfeus, was used to measure the three-dimensional spatial change in these structures after bony alignment. The required planning target volume margin for this spatial change, after bone alignment, was also calculated. Results: Rectal contrast was found to introduce a systematic error in the position of all organs compared with the noncontrast state. The largest change in structures during radiotherapy was in the anterior and posterior directions for the mesorectum and rectum and in the superior and inferior directions for the gross tumor volume. The planning target volume margins required for internal movement for the mesorectum based on the three scans acquired during treatment are 4 mm right, 5 mm left, 7 mm anterior, and 6 mm posterior. For the rectum, values were 8 mm right, 8 mm left, 8 mm anterior, and 9 mm posterior. The greatest movement of the rectum occurred in the upper third. Conclusions: Contrast is no longer used in CT simulation. Assuming bony alignment, a nonuniform margin of 8 mm anteriorly, 9 mm posteriorly, and 8 mm left and right is recommended.

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Three-Dimensional Analysis of Recurrence Patterns in Rectal Cancer: The Cranial Border in Hypofractionated Preoperative Radiotherapy Can Be Lowered

Purpose: The aim of this study was to determine whether and where the radiotherapy (RT) clinical target volume (CTV) could be reduced in short-course preoperative treatment of rectal cancer patients. Methods and Materials: Patients treated in the Dutch total mesorectal excision trial, with a local recurrence were analyzed. For 94 (25 who underwent radiation therapy 69 who did not) of 114 patients with a local recurrence, the location of the recurrence was placed in a three-dimensionalthree (3D) model. The data in the 3D model were correlated to the clinical trial data to distinguish a group of patients eligible for CTV reduction. Effects of CTV reduction on dose to the small bowel was tested retrospectively in a dataset of 8 patients with three-field conformal plans and intensity-modulated RT (IMRT). Results: The use of preoperative RT mainly reduces anastomotic, lateral, and perineal recurrences. In patients without primary nodal involvement, no recurrences were found cranially of the S2-S3 interspace, irrespective of the delivery of RT. In patients without primary nodal involvement and a negative circumferential resection margin (CRM), only one recurrence was found cranial to the S2-S3 interspace. With a cranially reduced CTV to the S2-S3 interspace, over 60% reduction in absolute small bowel exposure at dose levels from 15 to 35 Gy could be achieved with three-field conventional RT, increasing to 80% when IMRT is also added. Conclusions: The cranial border of the CTV can safely be lowered for patients without expected nodal or CRM involvement, yielding a significant reduction of dose to the small bowel. Therefore, a significant reduction of acute and late toxicity can be expected.

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Digital Tomosynthesis for Respiratory Gated Liver Treatment: Clinical Feasibility for Daily Image Guidance

Purpose: Breath-hold (BH) treatment minimizes internal target volumes (ITV) when treating sites prone to motion. Digital tomosynthesis (DTS) imaging has advantages over cone-beam CT (CBCT) for BH imaging: BH-DTS scan can be completed during a single breath-hold, whereas BH-CBCT is usually acquired by parsing the gantry rotation into multiple BH segments. This study evaluates the localization accuracy of DTS for BH treatment of liver tumors. Methods: Both planning CT and on-board DTS/CBCT images were acquired under BH, using the planning CT BH window as reference. Onboard imaging data sets included two independent DTS orientations (coronal and sagittal), and CBCT images. Soft tissue target positioning was measured by each imaging modality and translated into couch shifts. Performance of the two DTS orientations was evaluated by comparing target positioning with the CBCT benchmark, determined by two observers. Results: Image data sets were collected from thirty-eight treatment fractions (14 patients). Mean differences between the two DTS methods and the CBCT method were <1 mm in all directions (except the lateral direction with sagittal-DTS: 1.2 mm); the standard deviation was in the range of 2.1-3.5 mm for all techniques. The Pearson correlation showed good interobserver agreement for the coronal-DTS (0.72-0.78). The interobserver agreement for the sagittal-DTS was good for the in-plane directions (0.70-0.82), but poor in the out-of-plane direction (lateral, 0.26). Conclusions: BH-DTS may be a simpler alternative to BH-CBCT for onboard soft tissue localization of the liver, although the precision of DTS localization appears to be somewhat lower because of the presence of subtle out-of-plane blur.

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Intraoperative Radiotherapy for Unresectable Pancreatic Cancer: A Multi-Institutional Retrospective Analysis of 144 Patients

Purpose: To retrospectively analyze the results of intraoperative radiotherapy (IORT) + external beam radiotherapy (EBRT) for unresectable pancreatic cancer. Methods and Materials: The records of 144 patients treated with IORT, with or without, EBRT were reviewed. One hundred and thirteen patients (78.5%) were treated with IORT + EBRT and 114 patients (79.2%) were treated in conjunction with chemotherapy. The median doses of IORT and EBRT were 25 Gy and 45 Gy, respectively. The median follow-up of all 144 patients was 9.6 months (range, 0.5-69.7 months). Results: At the time of this analysis, 131 of 144 patients (91.0%) had disease recurrences. Local progression was observed in 60 patients (41.7%), and the 2-year local control (LC) rate in all patients was 44.6%. Patients treated with IORT, with or without, EBRT had significantly more favorable LC (2-year LC, 50.9%) than those treated with IORT without EBRT (p = 0.0004). The 2-year overall survival (OS) rate and the median survival time in all 144 patients were 14.7% and 10.5 months, respectively. Patients treated with chemotherapy had a significantly favorable OS than those treated without chemotherapy (p < 0.0001). On univariate analysis, chemotherapy use alone had a significant impact on OS and on multivariate analysis; chemotherapy use was a significant prognostic factor. Late gastrointestinal morbidity of National Cancer Institute-Common Terminology Criteria Grade 3 was observed in 2 patients (1.4%). Conclusion: IORT + EBRT yields a relatively favorable LC rate for unresectable pancreatic cancer with low frequency of severe late toxicity, and IORT combined with chemotherapy conferred a survival benefit compared with IORT without chemotherapy.

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Late Rectal Toxicity on RTOG 94-06: Analysis Using a Mixture Lyman Model

Purpose: To estimate the parameters of the Lyman normal-tissue complication probability model using censored time-to-event data for Grade {>=}2 late rectal toxicity among patients treated on Radiation Therapy Oncology Group 94-06, a dose-escalation trial designed to determine the maximum tolerated dose for three-dimensional conformal radiotherapy of prostate cancer. Methods and Materials: The Lyman normal-tissue complication probability model was fitted to data from 1,010 of the 1,084 patients accrued on Radiation Therapy Oncology Group 94-06 using an approach that accounts for censored observations. Separate fits were obtained using dose-volume histograms for whole rectum and dose-wall histograms for rectal wall. Results: With a median follow-up of 7.2 years, the crude incidence of Grade {>=}2 late rectal toxicity was 15% (n = 148). The parameters of the Lyman model fitted to dose-volume histograms data, with 95% profile-likelihood confidence intervals, were TD{sub 50} = 79.1 Gy (75.3 Gy, 84.3 Gy), m = 0.146 (0.107, 0.225), and n = 0.077 (0.041, 0.156). The fit based on dose-wall histogram data was not significantly different. Patients with cardiovascular disease had a significantly higher incidence of late rectal toxicity (p = 0.015), corresponding to a dose-modifying factor of 5.3%. No significant association with late rectal toxicity was found for diabetes, hypertension, rectal volume, rectal length, neoadjuvant hormone therapy, or prescribed dose per fraction (1.8 Gy vs. 2 Gy). Conclusions: These results, based on a large cohort of patients from a multi-institutional trial, are expected to be widely representative of the ability of the Lyman model to describe the long-term risk of Grade {>=}2 late rectal toxicity after three-dimensional conformal radiotherapy of prostate cancer.

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Volumetric Change of Selected Organs at Risk During IMRT for Oropharyngeal Cancer

Purpose: To assess volumetric changes of selected organs at risk (OAR) during intensity-modulated radiotherapy (IMRT) for oropharyngeal carcinoma. Materials and Methods: Twenty-six consecutive patients that were treated with definitive IMRT {+-} chemotherapy between November 2007 and November 2008 were selected for the present study. As part of an internal quality assurances program, a repeat kilovolt (KV) computed tomography was planned weekly during the 7-week treatment course. On each available scan, a single observer contoured the parotid submandibular, and thyroid glands (PG/SMG/TG), larynx (L), and constrictor, masticatory, and sternocleidomastoid muscles (CM/MM/SCM) as appropriate. The volume at each scan was compared with the one at planning CT in a pair-wise fashion. p values <0.05 after correction for multiple testing were considered significant. Results: A total of 159 scans was obtained during treatment for a total of 185 scans, including the baseline imaging. All OARs showed statistically significant changes over baseline by week 5. At week 7, the PG showed the largest absolute change with an average reduction of {approx}10 mL followed by both the SCM and MM ({approx}-5 mL). The largest ({approx}-30%) relative change was observed for the salivary glands. L and CM showed a {approx}15% increase in volume during treatment. Conclusion: All selected OAR undergo significant volumetric changes during a course of IMRT for oropharyngeal squamous cell carcinoma.

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Clinical Evaluation of Soft Tissue Organ Boundary Visualization on Cone-Beam Computed Tomographic Imaging

Purpose: Cone-beam computed tomographic images (CBCTs) are increasingly used for setup correction, soft tissue targeting, and image-guided adaptive radiotherapy. However, CBCT image quality is limited by low contrast and imaging artifacts. This analysis investigates the detectability of soft tissue boundaries in CBCT by performing a multiple-observer segmentation study. Methods and Materials: In four prostate cancer patients prostate, bladder and rectum were repeatedly delineated by five observers on CBCTs and fan-beam CTs (FBCTs). A volumetric analysis of contouring variations was performed by calculating coefficients of variation (COV: standard deviation/average volume). The topographical distribution of contouring variations was analyzed using an average surface mesh-based method. Results: Observer- and patient-averaged COVs for FBCT/CBCT were 0.09/0.19 for prostate, 0.05/0.08 for bladder, and 0.09/0.08 for rectum. Contouring variations on FBCT were significantly smaller than on CBCT for prostate (p < 0.03) and bladder (p < 0.04), but not for rectum (p < 0.37; intermodality differences). Intraobserver variations from repeated contouring of the same image set were not significant for either FBCT or CBCT (p < 0.05). Average standard deviations of individual observers' contour differences from average surface meshes on FBCT vs. CBCT were 1.5 vs. 2.1 mm for prostate, 0.7 vs. 1.4 mm for bladder, and 1.3 vs. 1.5 mm for rectum. The topographical distribution of contouring variations was similar for FBCT and CBCT. Conclusion: Contouring variations were larger on CBCT than FBCT, except for rectum. Given the well-documented uncertainty in soft tissue contouring in the pelvis, improvement of CBCT image quality and establishment of well-defined soft tissue identification rules are desirable for image-guided radiotherapy.

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Position Verification for the Prostate: Effect on Rectal Wall Dose

Purpose: To evaluate the effect of gold marker (GM)-based position correction on the cumulative dose in the anorectal wall compared with traditional bony anatomy (BA)-based correction, taking into account changes in anorectal shape and position. Methods and Materials: A total of 20 consecutive prostate cancer patients, treated with curative external beam radiotherapy, were included. Four fiducial GMs were implanted in the prostate. Positioning was verified according to the shift in BA and GMs on daily electronic portal images. Position corrections were determined using on- and off-line position verification protocols according to the position of the GMs (GM-on and GM-off) and BA (BA-off). For all patients, intensity-modulated radiotherapy plans were made for the GM (8-mm planning target volume margin) and BA (10-mm planning target volume margin) protocols. The dose distribution was recomputed on 11 repeat computed tomography scans to estimate the accumulated dose to the prostate and anorectal wall while considering internal organ motion. Results: The dose that is at least received by 99% of the prostate was, on average, acceptable for all protocols. The individual patient data showed the best coverage for both GM protocols, with >95% of the prescribed dose for all patients. The anorectal wall dose was significantly lower for the GM protocols. The dose that is at least received by 30% of the rectal wall was, on average, 54.6 Gy for GM-on, 54.1 Gy for GM-off, and 58.9 Gy for BA-off (p <.001). Conclusion: Position verification with GM and reduced planning target volume margins yielded adequate treatment of the prostate and a lower rectal wall dose, even when accounting for independent movement of the prostate and anorectal wall.

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Predictive Factors of Tumor Response After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

Purpose: Neoadjuvant chemoradiation followed by surgery is the standard of care for locally advanced rectal cancer. The aim of this study was to correlate tumor response to survival and to identify predictive factors for tumor response after chemoradiation. Methods and Materials: From 1998 to 2008, 168 patients with histologically proven locally advanced adenocarcinoma treated by preoperative chemoradiation before total mesorectal excision were retrospectively studied. They received a radiation dose of 45 Gy with a concomitant 5-fluorouracil (5-FU)-based chemotherapy. Analysis of tumor response was based on lowering of the T stage between pretreatment endorectal ultrasound and pathologic specimens. Overall and progression-free survival rates were correlated with tumor response. Tumor response was analyzed with predictive factors. Results: The median follow-up was 34 months. Five-year disease-free survival and overall survival rates were, of 44.4% and 74.5% in the whole population, 83.4% and 83.4%, respectively, in patients with pathological complete response, 38.6% and 71.9%, respectively, in patients with tumor downstaging, and 29.1and 58.9% respectively, in patients with absence of response. A pretreatment carcinoembryonic antigen (CEA) level of <5 ng/ml was significantly independently associated with pathologic complete tumor response (p = 0.019). Pretreatment small tumor size (p = 0.04), pretreatment CEA level of <5 ng/ml (p = 0.008), and chemotherapy with capecitabine (vs. 5-FU) (p = 0.04) were significantly associated with tumor downstaging. Conclusions: Downstaging and complete response after CRT improved progression-free survival and overall survival of locally advanced rectal adenocarcinoma. In multivariate analysis, a pretreatment CEA level of <5 ng/ml was associated with complete tumor response. Thus, small tumor size, a pretreatment CEA level of < 5ng/ml, and use of capecitabine were associated with tumor downstaging.

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Phase II Trial of Full-Dose Gemcitabine and Bevacizumab in Combination With Attenuated Three-Dimensional Conformal Radiotherapy in Patients With Localized Pancreatic Cancer

Purpose: To evaluate response rate, survival, and toxicity in patients with nonmetastatic pancreatic cancer treated with gemcitabine, bevacizumab, and radiotherapy. Methods and Materials: Patients received three cycles of therapy over 10 weeks. In total, treatment consisted of intravenous (IV) gemcitabine, 1,000 mg/m{sup 2}, every 1 to 2 weeks (7 doses), IV bevacizumab, 10 mg/kg every 2 weeks (5 doses), and 36 Gy of radiotherapy (2.4-Gy fractions during cycle two). Response was assessed by cross-sectional imaging and carbohydrate antigen 19-9 (CA 19-9) levels. Patients with resectable tumors underwent surgery 6 to 8 weeks after the last dose of bevacizumab. Maintenance gemcitabine and bevacizumab doses were delivered to patients who had unresected tumors and no progression. Results: Twenty-eight of the 32 enrolled patients completed all three cycles. The median follow-up was 11.07 months. Most grade 3 or 4 toxicities occurred in the initial treatment phase; the most frequent toxicities were leukopenia (21%), neutropenia (17%), and nausea (17%). At week 10, 1 patient (4%) had a complete response, 2 patients (7%) had partial responses, 21 patients (75%) had stable disease, and 4 patients (14%) had progressive disease. The median pretreatment and posttreatment CA 19-9 levels (25 patients) were 184.3 and 57.9 U/ml, respectively (p = 0.0006). One of 10 patients proceeding to surgery experienced a major complication. Two of 6 patients undergoing resection had complete pathologic responses. The median progression-free and overall survival durations were 9.9 months and 11.8 months, respectively. Conclusions: The combination of full-dose gemcitabine, bevacizumab, and radiotherapy was active and was not associated with a high rate of major surgical complications.

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Bevacizumab, Capecitabine, Amifostine, and Preoperative Hypofractionated Accelerated Radiotherapy (HypoArc) for Rectal Cancer: A Phase II Study

Purpose: Bevacizumab has established therapeutic activity in patients with metastatic colorectal cancer, and anti-vascular endothelial growth factor therapy enhances the activity of radiotherapy in experimental models. We assessed the feasibility and efficacy of preoperative radiochemotherapy combined with bevacizumab in patients with rectal cancer. Methods and Materials: Nineteen patients with radiologic T3 and/or N+ rectal carcinoma were treated with preoperative conformal hypofractionated accelerated radiotherapy (3.4 Gy in 10 consecutive fractions) supported with amifostine (500-1,000 mg daily), capecitabine (600 mg/m{sup 2} twice daily, 5 days per week), and bevacizumab (5 mg/kg every 2 weeks for 2 cycles). Surgery followed 6 weeks after the end of radiotherapy. A cohort of 14 sequential patients treated with the same regimen without bevacizumab was available for comparison. Results: Grade 2 or 3 diarrhea was noted in 7 of 19 patients (36.8%), which was statistically worse than patients receiving the same regimen without bevacizumab (p = 0.01). A higher incidence of Grade 2 or 3 proctalgia was also noted (21.1%) (p = 0.03). Bladder and skin toxicity was negligible. All toxicities regressed completely within 2 weeks after the end of therapy. Pathologic complete and partial response was noted in 7 of 19 cases (36.8%) and 8 of 19 cases (42.1%). Within a median follow-up of 21 months, none of the patients has had late complications develop and only 1 of 18 evaluable cases (5.5%) has had locoregional relapse. Conclusions: Bevacizumab can be safely combined with hypofractionated radiotherapy and capecitabine as a preoperative radiochemotherapy regimen for patients with rectal cancer. The high pathologic complete response rates urges the testing of bevacizumab in randomized studies.

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Intensity-Modulated Radiotherapy Reduces Gastrointestinal Toxicity in Patients Treated With Androgen Deprivation Therapy for Prostate Cancer

Purpose: Androgen deprivation therapy (AD) has been shown to increase late Grade 2 or greater rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. The present study compared the genitourinary and gastrointestinal (GI) toxicity in men treated with 3D-CRT+AD vs. IMRT+AD. Methods and Materials: Between July 1992 and July 2004, 293 men underwent 3D-CRT (n = 170) or IMRT (n = 123) with concurrent AD (<6 months, n = 123; {>=}6 months, n = 170). The median radiation dose was 76 Gy for 3D-CRT (International Commission on Radiation Units and Measurements) and 76 Gy for IMRT (95% to the planning target volume). Toxicity was assessed by a patient symptom questionnaire that was completed at each visit and recorded using a Fox Chase Modified Late Effects Normal Tissue Task radiation morbidity scale. Results: The mean follow-up was 86 months (standard deviation, 29.3) for the 3D-CRT group and 40 months (standard deviation, 9.7) for the IMRT group. Acute GI toxicity (odds ratio, 4; 95% confidence interval, 1.6-11.7; p = .005) was significantly greater with 3D-CRT than with IMRT and was independent of the AD duration (i.e., <6 vs. {>=}6 months). The interval to the development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimate for Grade 2 or greater GI toxicity was 20% for 3D-CRT and 8% for IMRT (p = .01). On multivariate analysis, Grade 2 or greater late GI toxicity (hazard ratio, 2.1; 95% confidence interval, 1.1-4.3; p = .04) was more prevalent in the 3D-CRT patients. Conclusion: Compared with 3D-CRT, IMRT significantly decreased the acute and late GI toxicity in patients treated with AD.

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Patterns of Response After Preoperative Treatment in Gastric Cancer

Purpose: To analyze the rate of pathologic response in patients with locally advanced gastric cancer treated with preoperative chemotherapy with and without chemoradiation at our institution. Methods and Materials: From 2000 to 2007 patients were retrospectively identified who received preoperative treatment for gastric cancer (cT3-4/ N+) with induction chemotherapy (Ch) or with Ch followed by concurrent chemoradiotherapy (45 Gy in 5 weeks) (ChRT). Surgery was planned 4-6 weeks after the completion of neoadjuvant treatment. Pathologic assessment was used to investigate the patterns of pathologic response after neoadjuvant treatment. Results: Sixty-one patients were analyzed. Of 61 patients, 58 (95%) underwent surgery. The R0 resection rate was 87%. Pathologic complete response was achieved in 12% of the patients. A major pathologic response (<10% of residual tumor) was observed in 53% of patients, and T downstaging was observed in 75%. Median follow-up was 38.7 months. Median disease-free survival (DFS) was 36.5 months. The only patient-, tumor-, and treatment-related factor associated with pathologic response was the use of preoperative ChRT. Patients achieving major pathologic response had a 3-year actuarial DFS rate of 63%. Conclusions: The patterns of pathologic response after preoperative ChRT suggest encouraging intervals of DFS. Such a strategy may be of interest to be explored in gastric cancer.

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High-Dose Split-Course Radiation Therapy for Anal Cancer: Outcome Analysis Regarding the Boost Strategy (CORS-03 Study)

Purpose: To retrospectively assess the clinical outcome in anal cancer patients treated with split-course radiation therapy and boosted through external-beam radiation therapy (EBRT) or brachytherapy (BCT). Methods and Materials: From January 2000 to December 2004, a selected group (162 patients) with invasive nonmetastatic anal squamous cell carcinoma was studied. Tumor staging reported was T1 = 31 patients (19%), T2 = 77 patients (48%), T3 = 42 patients (26%), and T4= 12 patients (7%). Lymph node status was N0-1 (86%) and N2-3 (14%). Patients underwent a first course of EBRT: mean dose 45.1 Gy (range, 39.5-50) followed by a boost: mean dose 17.9 Gy (range, 8-25) using EBRT (76 patients, 47%) or BCT (86 patients, 53%). All characteristics of patients and tumors were well balanced between the BCT and EBRT groups. Results: The mean overall treatment time (OTT) was 82 days (range, 45-143) and 67 days (range, 37-128) for the EBRT and BCT groups, respectively (p < 0.001). The median follow-up was 62 months (range, 2-108). The 5-year cumulative rate of local recurrence (CRLR) was 21%. In the univariate analysis, the prognostic factors for CRLR were as follows: T stage (T1-2 = 15% vs. T3-4 = 36%, p = 0.03), boost technique (BCT = 12% vs. EBRT = 33%, p = 0.002) and OTT (OTT <80 days = 14%, OTT {>=}80 days = 34%, p = 0.005). In the multivariate analysis, BCT boost was the unique prognostic factor (hazard ratio = 0.62 (0.41-0.92). In the subgroup of patients with OTT <80 days, the 5-year CRLR was significantly increased with the BCT boost (BC = 9% vs. EBRT = 28%, p = 0.03). In the case of OTT {>=}80 days, the 5-year CRLR was not affected by the boost technique (BCT = 29% vs. EBRT = 38%, p = 0.21). Conclusion: In anal cancer, when OTT is <80 days, BCT boost is superior to EBRT boost for CRLR. These results suggest investigating the benefit of BCT boost in prospective trials.

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Quantifying the Benefit of a Pathologic Complete Response After Neoadjuvant Chemoradiotherapy in the Treatment of Esophageal Cancer

Purpose: To better define the benefit of a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy in the treatment of esophageal and gastroesophageal cancer, we undertook a comprehensive review of the literature to derive a pooled analysis of crude survival data and quantify the survival benefit of pCR vs. residual disease at esophagectomy. Methods and Materials: In all, 22 articles were reviewed. Crude overall survival data, stratified by patients with pCR vs. those with residual disease at esophagectomy, were collected and analyzed using a chi-square analysis. The relative and absolute survival benefit of achieving a pCR were calculated and analyzed. Finally, stratified median survival times were also analyzed. Results: Overall survival for patients with pCR was 93.1%, 75.0%, and 50.0% at 2, 3, and 5 years, respectively, whereas it was 36.8%, 29.0%, and 22.6% for patients with residual tumor (p < 0.025). The mean relative survival benefit of pCR at 2, 3, and 5 years was 2.05, 2.35, and 2.84, respectively. The mean absolute survival benefit of pCR was 35.66%, 33.79%, and 33.20%, respectively. Median survival times for patients with pCR were significantly longer than for those with residual tumor (p = 0.011). Conclusion: In esophageal and gastroesophageal cancers, pCR seems to significantly increase overall survival in patients undergoing neoadjuvant chemoradiotherapy. Specifically, the data suggest that patients with pCR are two to three times more likely to survive than are those with residual tumor at esophagectomy. Moreover, these data suggest that 33-36% more patients survive when pCR is achieved than when it is not.

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Evaluation of Biologic Effective Dose and Schedule of Fractionation for Preoperative Radiotherapy for Rectal Cancer: Meta-Analyses and Meta-Regression;Rectal cancer; Preoperative radiotherapy; Biologic effective dose; Meta-analysis

Purpose: To evaluate whether the risk of local recurrence depends on the biologic effective dose (BED) or fractionation dose in patients with resectable rectal cancer undergoing preoperative radiotherapy (RT) compared with surgery alone. Methods and Materials: A meta-analysis of randomized controlled trials (RCTs) was performed. The MEDLINE, Embase, CancerLit, and Cochrane Library databases were systematically searched for evidence. To evaluate the dose-response relationship, we conducted a meta-regression analysis. Four subgroups were created: Group 1, RCTs with a BED >30 Gy{sub 10} and a short RT schedule; Group 2, RCTs with BED >30 Gy{sub 10} and a long RT schedule; Group 3, RCTs with BED {<=}30 Gy{sub 10} and a short RT schedule; and Group 4, RCTs with BED {<=}30 Gy{sub 10} and a long RT schedule. Results: Our review identified 21 RCTs, yielding 9,097 patients. The pooled results from these 21 randomized trials of preoperative RT showed a significant reduction in mortality for groups 1 (p = .004) and 2 (p = .03). For local recurrence, the results were also significant in groups 1 (p = .00001) and 2 (p = .00001).The only subgroup that showed a greater sphincter preservation (SP) rate than surgery was group 2 (p = .03). The dose-response curve was linear (p = .006), and RT decreased the risk of local recurrence by about 1.7% for each Gy{sub 10} of BED. Conclusion: Our data have shown that RT with a BED of >30 Gy{sub 10} is more efficient in reducing local recurrence and mortality rates than a BED of {<=}30 Gy{sub 10}, independent of the schedule of fractionation used. A long RT schedule with a BED of >30 Gy{sub 10} should be recommended for sphincter preservation.

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Proton Beam Therapy for Hepatocellular Carcinoma Located Adjacent to the Alimentary Tract;Proton beam therapy; Hepatocellular carcinoma; Gastrointestinal bleeding

Purpose: To evaluate the safety and effectiveness of proton beam therapy for hepatocellular carcinoma (HCC) located adjacent to the alimentary tract. Patients and Methods: Forty-seven patients (median age, 69 years; range, 43-82 years) who had HCC located within 2 cm of the alimentary tract underwent proton beam therapy. Liver damage according to the Child-Pugh classification was Class A in 35 patients, Class B in 9, and Class C in 3. Treatment protocols of the early 16 patients and the late 31 patients were 72.6 GyE in 22 fractions and 77 GyE in 35 fractions, respectively. Results: During the median follow-up period of 23 months, 24 patients died; the remaining 23 patients were alive until September 2008. The median overall survival was 33.9 months (95% confidence interval [CI], 10.8-57.0 months). Actuarial overall and local progression-free survival rates at 3 years were 50.0% and 88.1%, respectively. Grade 2 and 3 alimentary tract hemorrhage was observed in 3 (6.4%) and 1 (2.1%) patients, respectively. Conclusions: Our proton beam therapy strategy for HCC located adjacent to the alimentary tract seems to be effective but should be performed with caution.

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Chest Wall Toxicity After Stereotactic Body Radiotherapy for Malignant Lesions of the Lung and Liver

Purpose: To quantify the frequency of rib fracture and chest wall (CW) pain and identify the dose-volume parameters that predict CW toxicity after stereotactic body radiotherapy (SBRT). Methods and Materials: The records of patients treated with SBRT between 2000 and 2008 were reviewed, and toxicity was scored according to Common Terminology Criteria for Adverse Events v3.0 for pain and rib fracture. Dosimetric data for CW and rib were analyzed and related to the frequency of toxicity. The risks of CW toxicity were then further characterized according to the median effective concentration (EC{sub 50}) dose-response model. Results: A total of 347 lesions were treated with a median follow-up of 19 months. Frequency of Grade I and higher CW pain and/or fracture for CW vs. non-CW lesions was 21% vs. 4%, respectively (p < 0.0001). A dose of 50 Gy was the cutoff for maximum dose (Dmax) to CW and rib above which there was a significant increase in the frequency of any grade pain and fracture (p = 0.03 and p = 0.025, respectively). Volume of CW receiving 15 Gy - 40 Gy was highly predictive of toxicity (R{sup 2} > 0.9). According to the EC{sub 50} model, 5 cc and 15 cc of CW receiving 40 Gy predict a 10% and 30% risk of CW toxicity, respectively. Conclusion: Adequate tumor coverage remains the primary objective when treating lung or liver lesions with SBRT. To minimize toxicity when treating lesions in close proximity to the CW, Dmax of the CW and/or ribs should remain <50 Gy, and <5 cc of CW should receive {>=}40 Gy.

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