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Purpose Several recent series evaluating external beam accelerated partial breast irradiation (PBI) have reported adverse cosmetic outcomes, possibly related to large volumes of normal tissue receiving near-prescription doses. We hypothesized that delivery of external beam PBI in a single fraction to the preoperative tumor volume would be feasible and result in a decreased dose to the uninvolved breast compared with institutional postoperative PBI historical controls. Methods and Materials A total of 17 patients with unifocal Stage T1 breast cancer were identified. Contrast-enhanced subtraction magnetic resonance images were loaded into an Eclipse treatment planning system and used to define the target volumes. A "virtual plan" was created using four photon beams in a noncoplanar beam arrangement and optimized to deliver 15 Gy to the planning target volume. Results The median breast volume was 1,713 cm 3 (range: 1,014–2,140), and the median clinical target volume was 44 cm 3 (range: 26–73). In all cases, 100% of the prescription dose covered 95% of the clinical target volume. The median conformity index was 0.86 (range: 0.70–1.12). The median percentage of the ipsilateral breast volume receiving 100% and 50% of the prescribed dose was 3.8% (range: 2.2–6.9) and 13.3% (range: 7.5–20.8) compared with 18% (range: 3–42) and 53% (range: 24–65) in the institutional historical controls treated with postoperative external beam PBI ( p = .002). The median maximum skin dose was 9 Gy. The median dose to 1 and 10 cm 3 of skin was 6.7 and 4.9 Gy. The doses to the heart and ipsilateral lung were negligible. Conclusion Preoperative PBI resulted in a substantial reduction in ipsilateral breast tissue dose compared with postoperative PBI. The skin dose appeared reasonable, given the small volumes. A prospective Phase I trial evaluating this technique is ongoing.

Ampullary carcinoma is a rare malignancy. Despite radical resection, survival rates remain low with high rates of local failure. We performed a single-institution outcomes analysis to define the role of concurrent chemoradiotherapy (CRT) in addition to surgery. A retrospective analysis was performed of all patients undergoing potentially curative pancreaticoduodenectomy for adenocarcinoma of the ampulla of Vater at Duke University Hospitals between 1976 and 2009. Time-to-event analysis was performed comparing all patients who underwent surgery alone to the cohort of patients receiving CRT in addition to surgery. Local control (LC), disease-free survival (DFS), overall survival (OS), and metastases-free survival (MFS) were estimated using the Kaplan–Meier method. A total of 137 patients with ampullary carcinoma underwent Whipple procedure. Of these, 61 patients undergoing resection received adjuvant (n = 43) or neoadjuvant (n = 18) CRT. Patients receiving chemoradiotherapy were more likely to have poorly differentiated tumors (P = .03). Of 18 patients receiving neoadjuvant therapy, 67% were downstaged on final pathology with 28% achieving pathologic complete response (pCR). With a median follow-up of 8.8 years, 3-year local control was improved in patients receiving CRT (88% vs 55%, P = .001) with trend toward 3-year DFS (66% vs 48%, P = .09) and OS (62% vs 46%, P = .074) benefit in patients receiving CRT. Long-term survival rates are low and local failure rates high following radical resection alone. Given patterns of relapse with surgery alone and local control benefit in patients receiving CRT, the use of chemoradiotherapy in selected patients should be considered.

Purpose In the last 2 decades, guidelines have been developed to improve quality of patient care. A recent editorial of guideline development procedures suggested the process has significant limitations that affect their scientific validity. 1 This prompted us to review oncology treatment guidelines to determine if such limitations are widespread. Methods and Materials We performed a review of oncology treatment guidelines registered at the National Guidelines Clearinghouse (www.guideline.gov). Each guideline was independently reviewed by 2 authors and the following criteria were assessed: coordinating organization, guideline panel composition, reporting conflict of interest, peer review, dissent, expiration date, PubMed citation, and evidence-based scoring and grading of recommendations. Disagreements were resolved by consensus in subsequent discussions. Results Sixty-four guidelines were reviewed (39 [61%] were developed by a medical specialty society and 25 [39%] were developed by government agencies). Fifty (78%) guideline panels were multidisciplinary and 44 (69%) included individuals with epidemiologic and health services research expertise. Potential conflicts of interest were disclosed in 43 (67%) guidelines. Sixty (94%) guidelines underwent peer review, with external review in 31 (48%). Seventeen (27%) guidelines are indexed by PubMed. Fifty-one (80%) guidelines included evidence-based methodologies and 46 (72%) used evidence-based scoring of recommendations. Significant differences were observed according to coordinating organization (eg, disclosure of conflict of interest in 46% of guidelines developed by medical specialty societies versus 100% authored by government agencies [ P Conclusions The majority of oncology-related treatment guidelines registered at the National Guidelines Clearinghouse satisfy most of the criteria for sound guideline development. Significant differences in these criteria were observed according to the coordinating organization that developed the guideline.

Several clinical trials have addressed the role of adjuvant chemotherapy following neoadjuvant chemoradiation and surgery for rectal cancer. The recently published EORTC 22921 study adds further debate to the merits of adjuvant chemotherapy in this setting.

Background: Radiotherapy for left sided breast cancer potentially increases risk for late toxicity to the heart. The simple technique of breath-hold (BH) can be instituted in an attempt to reduce volume of lung and heart irradiated in tangential fields. We report on patients with left sided breast cancer that were planned both with conventional free-breathing (FB) and BH radiation techniques from a single institution. Methods: From 10/2006 to 5/2010, 20 patients with node-negative, early stage breast cancer underwent CT simulation for left sided breast cancer and were selected for analysis in this report. FB and BH CT scans were obtained and treatment plans using opposed tangential fields were created to compare various dosimetric indices. Results: BH plans resulted in lower doses to the heart (max dose 1774 vs. 4560cGy, P Conclusions: Treatment of early stage left sided breast cancer with BH technique is a simple method for minimizing cardiac and ipsilateral lung dose. Long term follow-up is necessary to demonstrate if these dosimetric differences translate into clinically meaningful differences. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-21.

4121Background: The optimal management of potentially resectable pancreas cancer is unknown. The high rates of local and distant failures following surgical resection highlights the need for improv...

741 Background: Adjuvant chemotherapy (AC) following chemoradiation (CRT) and total mesorectal excision (TME) for locoregionally advanced rectal cancer (LARC) is a standard of care in the United States despite limited data. The purpose of this study was to examine the role, optimal regimen, and duration of AC in the mandatory, prospectively collected cancer registry of the largest integrated health system in the US. Methods: Using the VA Central Cancer Registry, stage II-III rectal cancer patients diagnosed between 1/2001-4/2011 were included if they received neoadjuvant CRT followed by TME with or without AC. Adequate chemotherapy was defined as at least 4 months of therapy. Kaplan-Meier and Log-Rank tests were used to assess survival. Propensity score (PS) adjustment was performed to compare survival outcomes while adjusting for baseline characteristics, including AJCC stage, age, gender, race, smoking status, and comorbidity. Results: 649 patients were identified; 323 received AC while 326 did not (OBS). Median follow-up was 66 months. Mean age was 63 years. 85.1% were white; 98.8% were male. 49.2% had stage II disease. Median overall survival (OS) for all patients was 92 months; 6-year OS was 56.8%. Median OS was 72 months for the OBS group and not reached (NR) for the AC group (p < 0.001). OS at 6 years was 49.5% for OBS and 64.1% for AC (p < 0.0001). On PS matched analysis, OS was improved favoring AC (p < 0.0001). Median disease-specific survival (DSS) was NR for the whole group and NR for the OBS and AC groups. 6-year DSS was 73.6% for the whole group and 67.9% for OBS vs. 79.2% for AC (p < 0.001). PS matched analysis for DSS favored AC (p = 0.0004). There was no significant difference in OS (p = 0.554) or DSS (p = 0.680) when comparing single versus multi-agent chemotherapy and no significant difference in OS (p = 0.766) or DSS (p = 0.271) when comparing adequate ( > / = 4 months) versus inadequate chemotherapy ( < 4 months). Conclusions: In this VA population of LARC patients treated with neoadjuvant CRT followed by TME, the addition of AC was found to improve both OS and DSS compared to OBS. There was no improvement in OS or DSS with the addition of a multi-agent over single-agent chemotherapy.

The optimal approach to patients with locally recurrent, non-metastatic rectal cancer is unclear. This study evaluates the outcomes and toxicity associated with pelvic re-irradiation. Patients undergoing re-irradiation for locally recurrent, non-metastatic, rectal cancer between 2000 and 2014 were identified. Acute and late toxicities were assessed using common terminology criteria for adverse events version 4.0. Disease-related endpoints included palliation of local symptoms, surgical outcomes, and local progression-free survival (PFS), distant PFS and overall survival (OS) using the Kaplan–Meier method. Thirty-three patients met the criteria for inclusion in this study. Two (6 %) experienced early grade 3+ toxicity and seven (21 %) experienced late grade 3+ toxicity. Twenty-three patients presented with symptomatic local recurrence and 18 (78 %) reported symptomatic relief. Median local PFS was 8.7 (95 % CI 3.8–15.2) months, with a 2-year rate of 15.7 % (4.1–34.2), and median time to distant progression was 4.4 (2.2–33.3) months, with a 2-year distant PFS rate of 38.9 % (20.1–57.3). Median OS time for patients was 23.1 (11.1–33.0) months. Of the 14 patients who underwent surgery, median survival was 32.3 (13.8–48.0) months compared with 13.3 (2.2–33.0) months in patients not undergoing surgery (p = 0.10). A margin-negative (R0) resection was achieved in 10 (71 %) of the surgeries. Radiation treatment modality (intensity-modulated radiation therapy, three-dimensional conformal radiotherapy, intraoperative radiation therapy) did not influence local or distant PFS or OS. Re-irradiation is a beneficial treatment modality for the management of locally recurrent, non-metastatic rectal cancer. It is associated with symptom improvement, low rates of toxicity, and similar benefits among radiation modalities.

Hypofractionated radiation therapy (RT) has promising long-term biochemical relapse-free survival (bRFS) with comparable toxicity for definitive treatment of prostate cancer. However, data reporting outcomes after adjuvant and salvage postprostatectomy hypofractionated RT are sparse. Therefore, we report the toxicity and clinical outcomes after postprostatectomy hypofractionated RT.From a prospectively maintained database, men receiving image guided hypofractionated intensity modulated RT (HIMRT) with 2.5-Gy fractions constituted our study population. Androgen deprivation therapy was used at the discretion of the radiation oncologist. Acute toxicities were graded according to the Common Terminology Criteria for Adverse Events version 4.0. Late toxicities were scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Biochemical recurrence was defined as an increase of 0.1 in prostate-specific antigen (PSA) from posttreatment nadir or an increase in PSA despite treatment. The Kaplan-Meier method was used for the time-to-event outcomes.Between April 2008 and April 2012, 56 men received postoperative HIMRT. The median follow-up time was 48 months (range, 21-67 months). Thirty percent had pre-RT PSA0.1; the median pre-RT detectable PSA was 0.32 ng/mL. The median RT dose was 65 Gy (range, 57.5-65 Gy). Ten patients received neoadjuvant and concurrent hormone therapy. Posttreatment acute urinary toxicity was limited. There was no acute grade 3 toxicity. Late genitourinary (GU) toxicity of any grade was noted in 52% of patients, 40% of whom had pre-RT urinary incontinence. The 4-year actuarial rate of late grade 3 GU toxicity (exclusively gross hematuria) was 28% (95% confidence interval [CI], 16%-41%). Most grade 3 GU toxicity resolved; only 7% had persistent grade ≥3 toxicity at the last follow-up visit. Fourteen patients experienced biochemical recurrence at a median of 20 months after radiation. The 4-year bPFS rate was 75% (95% CI, 63%-87%).The biochemical control in this series appears promising, although relatively short follow-up may lead to overestimation. Late grade 3 GU toxicity was higher than anticipated with hypofractionated radiation of 65 Gy to the prostate bed, although most resolved.

Surgery has long been the primary curative modality for localized rectal cancer. Neoadjuvant chemoradiation has significantly improved local control rates and, in a significant minority, eradicated all disease. Patients who achieve a pathologic complete response to neoadjuvant therapy have an excellent prognosis, although the combination treatment is associated with long-term morbidity. Because of this, a nonoperative management (NOM) strategy has been pursued to preserve sphincter function in select patients. Clinical and radiographic findings are used to identify patients achieving a clinical complete response to chemoradiation, and they are then followed with intensive surveillance. Incomplete, nonresponding and those demonstrating local progression are referred for salvage with standard surgery. Habr-Gama and colleagues have published extensively on this treatment strategy and have laid the groundwork for this approach. This watch-and-wait strategy has evolved over time, and several groups have now reported their results, including recent prospective experiences. Although initial results appear promising, several significant challenges remain for NOM of rectal cancer. Further study is warranted before routine implementation in the clinic.

Purpose Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Methods and Materials Women aged ≥55 years with clinically node-negative, estrogen receptor–positive, and/or progesterone receptor–positive HER2−, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed. Results No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. Conclusions Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should be tested in future clinical trials because it has the potential to challenge the current treatment paradigm and provide a path forward to identify radiation response biomarkers.

Cancer development in the cervical portion of the esophagus presents a unique challenge to management given the close proximity of critical structures in the head and neck. Cervical esophageal cancer (CEC) was historically approached with primary surgery, pharyngo-laryngo-esophagectomy (PLE), but a paradigm shift has occurred such that functional organ preservation with concurrent chemotherapy and radiation (CRT) is now preferred. This chapter will review anatomical considerations pertinent to the management of CEC as well as the risk factors and multidisciplinary treatment approach to this disease.

Radiation therapy with concurrent chemotherapy is the standard treatment for patients with nonmetastatic squamous cell carcinoma of the anal canal. In the studies that established this approach, high rates of locoregional control have been reported, but the incidence of acute and late toxicity has been significant. Moreover, treatment-related acute toxicity may cause treatment interruptions that are potentially detrimental to locoregional control and colostomy-free survival. Intensity-modulated radiation therapy (IMRT) has recently been instituted as an alternative to conventional two-dimensional (2D) or three-dimensional (3D) conformal radiotherapy. Multiple institutional experiences, as well as a single phase II multi-institution prospective study, have demonstrated improved acute toxicity rates with IMRT, potentially minimizing treatment interruptions and improving treatment outcomes. Pilot studies evaluating IMRT show no reduction in overall or colostomy-free survival versus historical studies. Due to its high precision, the use of IMRT in anal cancer requires thorough understanding of the patterns of spread of anal cancer with thoughtful delineation of target volumes and organs at risk. In this chapter, we highlight the available data on the use of IMRT for anal cancer and summarize established approaches for IMRT planning in this disease.

Purpose: To enable near-real-time (

A four-dimensional magnetic resonance imaging (4-D-MRI) technique with Sagittal-Coronal-Diaphragm Point-of-Intersection (SCD-PoI) as a respiratory surrogate is proposed. To develop an image-based respiratory surrogate, the SCD-PoI motion tracking method is used for retrospective 4-D-MRI reconstruction. Single-slice sagittal MR cine was acquired at a location near the center of the diaphragmatic dome. Multiple-slice coronal MR cines were acquired for 4-D-MRI reconstruction. As a motion surrogate, the diaphragm motion was measured from the PoI among the sagittal MRI cine plane, coronal MRI cine planes, and the diaphragm surface. These points were defined as the SCD-PoI. This point is used as a one-dimensional diaphragmatic navigator in our study. The 4-D-MRI technique was evaluated on a 4-D digital extended cardiac-torso (XCAT) human phantom, a motion phantom, and seven human subjects (five healthy volunteers and two cancer patients). Motion trajectories of a selected region of interest were measured on 4-D-MRI and compared with the known XCAT motion that served as references. The mean absolute amplitude difference ([Formula: see text]) and the cross-correlation coefficient (CC) of the comparisons were determined. 4-D-MRI of the XCAT phantom demonstrated highly accurate motion information ([Formula: see text], [Formula: see text]). Motion trajectories of the motion phantom measured on 4-D-MRI matched well with the references ([Formula: see text], [Formula: see text]). 4-D-MRI of human subjects showed minimal artifacts and clearly revealed the respiratory motion of organs and tumor (mean [Formula: see text]; mean [Formula: see text]). A 4-D-MRI technique with image-based respiratory surrogate has been developed and tested on phantoms and human subjects.

Failing to complete chemotherapy adversely affects survival in patients with colorectal cancer. However, the effect of incomplete delivery of neoadjuvant radiotherapy is unclear.To determine whether incomplete radiotherapy delivery is associated with worse clinical outcomes and survival.Data on 17 600 patients with stage II to III rectal adenocarcinoma from the 2006-2012 National Cancer Database who received neoadjuvant chemoradiotherapy followed by surgical resection were included. Multivariable regression methods were used to compare resection margin positivity, permanent colostomy rate, 30-day readmission, 90-day mortality, and overall survival between patients who received complete (45.0-50.4 Gy) and incomplete (45.0 Gy) doses of radiation as preoperative therapy.The primary outcome measure was overall survival; short-term perioperative and oncologic outcomes encompassing margin positivity, permanent ostomy rate, postoperative readmission, and postoperative mortality were also assessed.Among 17 600 patients included, 10 862 were men, with an overall median age of 59 years (range, 51-68 years). Of these, 874 patients (5.0%) received incomplete doses of neoadjuvant radiation. The median radiation dose received among those who did not achieve complete dosing was 34.2 Gy (interquartile range, 19.8-40.0 Gy). Female sex (adjusted odds ratio [OR] 0.69; 95% CI, 0.59-0.81; P .001) and receiving radiotherapy at a different hospital than the one where surgery was performed (OR, 0.72; 95% CI, 0.62-0.85; P .001) were independent predictors of failing to achieve complete dosing; private insurance status was predictive of completing radiotherapy (OR, 1.60; 95% CI, 1.16-2.21; P = .004). At 5-year follow-up, overall survival was improved among patients who received a complete course of radiotherapy (3086 [estimated survival probability, 73.2%] vs 133 [63.0%]; P .001). After adjustment for demographic, clinical, and tumor characteristics, patients receiving a complete vs incomplete radiation dose had a similar resection margin positivity (OR, 0.99; 95% CI, 0.72-1.35; P = .92), permanent colostomy rate (OR, 0.96; 95% CI, 0.70-1.32; P = .81), 30-day readmission rate (OR, 0.92; 95% CI, 0.67-1.27; P = .62), and 90-day mortality (OR, 0.72; 95% CI, 0.33-1.54; P = .41). However, a complete radiation dose had a significantly lower risk of long-term mortality (adjusted hazard ratio, 0.70; 95% CI, 0.59-0.84; P .001).Achieving a target radiation dose of 45.0 to 50.4 Gy is associated with a survival benefit in patients with locally advanced rectal cancer. Aligning all aspects of multimodal oncology care may increase the probability of completing neoadjuvant therapy.

175 Background: In this prospective study we evaluated whether changes in metabolic tumor parameters on interim flurodeoxyglucose positron emission tomography (FDG-PET) performed during neoadjuvant chemoradiotherapy (CRT) for esophageal cancer correlates with histopathologic tumor response. Methods: From February 2012 to February 2016, 60 patients with esophageal cancer underwent PET scans before therapy and after 30-36 Gy. Patients who underwent surgery after carboplatin/paclitaxel CRT were eligible for the current analysis. PET metrics of the primary site including maximum standardized uptake value (SUVmax), SUV mean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were extracted from the pre-treatment and interim PET based on a manual contour and SUV 2.5 threshold. Patients were called histopathologic responders if they had a complete or near complete tumor response based on the modified Ryan scheme. Relative changes in PET metrics between pre-treatment and interim PET were compared between histopathologic responders and non-responders using the Mann-Whitney test and binary logistic regression. Results: Twenty-six patients were included in the analysis. Adenocarcinoma was the most common histology (n = 23). Eleven patients (42%) had a complete or near complete pathologic response to CRT (histopathologic responders). Changes in PET metrics from pre-treatment to interim PET based on the manual contour were not significantly different between responding and nonresponding tumors. The relative reduction of SUVmax (Mean ± SD) was 38.2% ± 28.4% for histopathologic responders and 27.9% ± 31.4% for non-responders. The relative reduction in MTV, SUV mean and TLG was 36.1% ± 26.2%, 23.5% ± 21.3%, and 49.3% ± 28.3% for histopathologic responders and 28.6% ± 32.0%, 11.8% ± 19.1%, and 33.1% ± 38.5% for histopathologic non-responders, respectively. When analyzed based on the SUV 2.5 threshold there continued to be no significant difference in PET metrics. Conclusions: In this pilot study we observed changes in metabolic tumor parameters on PET performed during CRT for esophageal cancer. However, these changes did not predict for histopathologic responders.

Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates.

therapy does not improve survival and increases postoperative mortality in patients with early-stage disease. 13 However, patterns of failure analysis showed a significant improvement in local control in patients who were assigned to receive neoadjuvant therapy, nearly halving the rate of locoregional recurrence (29% v 15%). Disease recurrence rates were also significantly reduced in patients receiving neoadjuvanttreatment.TheselocalfailureratesmirrortheDutchtrial ratesoflocoregionalrecurrencereductionfrom34%(surgeryonly)to 14%(neoadjuvanttherapyandsurgery)inamoreadvancedgroupof patients.Thesedatahighlightthechallengeofsurgeryinextirpatingall locoregional disease even in patients with early-stage disease. How does one reconcile the differences in survival outcomes betweentheFrenchandDutchstudies?Thereareseveralpossibilities. First, small patient numbers in the FFCD 9901 trial reduce the statistical power of detecting a survival benefit, such as that seen in the Dutch study, despite similar reduction in disease recurrence rates in patients receiving neoadjuvant treatment. Next, the histologic subtypesweredifferentinthesetwostudies.Seventypercentofpatientsin the French study had a histologic diagnosis of squamous cell carcinoma compared with 23% in the Dutch study. Squamous cell carcinoma is a malignancy often arising in patients with longstanding histories of alcohol and tobacco use and associated comorbidities, whereas esophageal adenocarcinoma is associated with obesity, gastroesophageal reflux disease, and Barrett’s disease. The underlying biology and natural history of these two malignancies is different. Finally, the French study included more patients with early-stage disease(fewernode-positiveandT3patients)withcorrespondinghigh

There is significant debate regarding the optimal neoadjuvant regimen for resectable rectal cancer patients. Short-course radiotherapy, a standard approach throughout most of northern Europe, is generally defined as 25 Gy in 5 fractions over the course of 1 week without the concurrent administration of chemotherapy. Long-course radiotherapy is typically defined as 45 to 50.4 Gy in 25–28 fractions with the administration of concurrent 5-fluoropyrimidine-based chemotherapy and is the standard approach in other parts of Europe and the United States. At present, two randomized trials have compared outcomes for short course radiotherapy with long-course chemoradiation showing no difference in respective study endpoints. Late toxicity data are lacking given limited follow-up. Although the ideal neoadjuvant regimen is controversial, our current bias is long-course chemoradiation to treat patients with locally advanced, resectable rectal cancer.

The Cancer and Leukemia Group B (CALGB) 9343 randomized phase 3 trial established lumpectomy and adjuvant therapy with tamoxifen alone, rather than both radiotherapy and tamoxifen, as a reasonable treatment course for women aged70 years with clinical stage I (AJCC 7th edition), estrogen receptor-positive breast cancer. An analysis of the Surveillance, Epidemiology, and End Results (SEER) registry was undertaken to assess practice patterns before and after the publication of this landmark study.The SEER database from 2000 to 2009 was used to identify 40,583 women aged ≥70 years who were treated with breast-conserving surgery for clinical stage I, estrogen receptor-positive and/or progesterone receptor-positive breast cancer. The percentage of patients receiving radiotherapy and the type of radiotherapy delivered was assessed over time. Administration of radiotherapy was further assessed across age groups; SEER cohort; and tumor size, grade, and laterality.Approximately 68.6% of patients treated between 2000 and 2004 compared with 61.7% of patients who were treated between 2005 and 2009 received some form of adjuvant radiotherapy (P.001). Coinciding with a decline in the use of external beam radiotherapy, there was an increase in the use of implant radiotherapy from 1.4% between 2000 and 2004 to 6.2% between 2005 to 2009 (P.001). There were significant reductions in the frequency of radiotherapy delivery over time across age groups, tumor size, and tumor grade and regardless of laterality (P.001 for all).Randomized phase 3 data support the omission of adjuvant radiotherapy in elderly women with early-stage breast cancer. Analysis of practice patterns before and after the publication of these data indicates a significant decline in radiotherapy use; however, nearly two-thirds of women continue to receive adjuvant radiotherapy.

Intraoperative radiation therapy (IORT) techniques allow for the delivery of high doses of radiation therapy while excluding part or all of the nearby dose-limiting sensitive structures. Therefore, the effective radiation dose is increased and local tumor control potentially improved. This is pertinent in the case of pancreatic cancer because local failure rates are as high as 50%-80% in patients with resected and locally advanced disease. Available data in patients receiving IORT after pancreaticoduodenectomy reveal an improvement in local control, though overall survival benefit is unclear. Series of patients with locally advanced pancreatic cancer also suggest pain relief, and in select studies, improved survival associated with the inclusion of IORT. At present, no phase III data clearly supports the use of IORT in the management of pancreatic cancer.

Stereotactic body radiotherapy (SBRT) involves the treatment of extracranial primary tumors or metastases with a few, high doses of ionizing radiation. In SBRT, tumor kill is maximized and dose to surrounding tissue is minimized, by precise and accurate delivery of multiple radiation beams to the target. This is particularly challenging, because extracranial lesions often move with respiration and are irregular in shape, requiring careful treatment planning and continual management of this motion and patient position during irradiation. This review presents the rationale, process workflow, and technology for the safe and effective administration of SBRT, as well as the indications, outcome, and limitations for this technique in the treatment of lung cancer, liver cancer, and metastatic disease.

Purpose: To determine the variation in tumor contrast between different MRI sequences and between patients for the purpose of MRI-based treatment planning. Methods: Multiple MRI scans of 11 patients with cancer(s) in the liver were included in this IRB-approved study. Imaging sequences consisted of T1W MRI, Contrast-Enhanced T1W MRI, T2W MRI, and T2*/T1W MRI. MRI images were acquired on a 1.5T GE Signa scanner with a four-channel torso coil. We calculated the tumor-to-tissue contrast to noise ratio (CNR) for each MR sequence by contouring the tumor and a region of interest (ROI) in a homogeneous region of the liver using the Eclipse treatment planning software. CNR was calculated (I_Tum-I_ROI)/SD_ROI, where I_Tum and I_ROI are the mean values of the tumor and the ROI respectively, and SD_ROI is the standard deviation of the ROI. The same tumor and ROI structures were used in all measurements for different MR sequences. Inter-patient Coefficient of variation (CV), and inter-sequence CV was determined. In addition, mean and standard deviation of CNR were calculated and compared between different MR sequences. Results: Our preliminary results showed large inter-patient CV (range: 37.7% to 88%) and inter-sequence CV (range 5.3% to 104.9%) of liver tumor CNR, indicating great variations in tumor CNR between MR sequences and between patients. Tumor CNR was found to be largest in CE-T1W (8.5±7.5), followed by T2W (4.2±2.4), T1W (3.4±2.2), and T2*/T1W (1.7±0.6) MR scans. The inter-patient CV of tumor CNR was also the largest in CE-T1W (88%), followed by T1W (64.3%), T1W (56.2%), and T2*/T1W (37.7) MR scans. Conclusion: Large inter-sequence and inter-patient variations were observed in liver tumor CNR. CE-T1W MR images on average provided the best tumor CNR. Efforts are needed to optimize tumor contrast and its consistency for MRI-based treatment planning of cancer in the liver. This project is supported by NIH grant: 1R21CA165384

Purpose: To develop a clinically feasible workflow of 4D MRI-based treatment planning for liver SBRT. Methods: A clinical workflow based on 4D MRI for liver SBRT was designed to largely simulate the same procedure as 4D CT for lung SBRT. Key features of the workflow include: (1) contouring tumor volume at each phases (2) contouring more structures, (3) assigning CT numbers to structures for dose calculation. Uncertainties (bone delineation, MRI distortion, CT number assignment, etc.) were investigated using five clinical treatment plans of liver SBRT by simulating the following scenarios: homogeneous calculation, calculation with CT number assignment (for each structure separately and for all combined), calculation with and without distortion (mimicked by shirking body structure by 1mm to 5 mm). Dose-histogram volume (DVF) parameters were collected from the simulated cases and compared to those in the original plan. Lastly, a patient example case of 4D MRI-based treatment plan was performed to demonstrate the feasibility of the proposed workflow. Results: In homogeneous calculation, the average percentage volume error (ΔV30) of liver was 0.40% and maximum average dose error (GTV ΔD95) was 1.08Gy. Between MRI-based and original plans, liver ΔV30 was 0.28% and maximum average dose error (GTV ΔD95) was 0.75Gy. Basically dose errors and percentage volume error increased as distortion increased. In some special cases, in original plans, the minimum spinal cord max dose error appeared when distortion was 4mm; in MRI-based plans, the minimum liver ΔV30 appeared when distortion was 3mm. In the example case, mean liver dose was 20.7Gy in 4D MRI-based plan and 34.2Gy in 4D CT-based plan. Conclusion: A clinically feasible workflow of 4D MRI-based treatment planning for liver SBRT has been established. Dose uncertainties of the workflow were generally small, except for large MR geometric distortions (> 3 mm). NIH (1R21CA165384)

657 Background: Prospective randomized trials have demonstrated that neoadjuvant chemoradiation improves local control and results in a higher rate of sphincter-sparing surgery for patients with locally advanced rectal cancer. However, neoadjuvant therapy utilization and population-based outcomes are not well defined. Methods: Adults with stage II/III rectal adenocarcinoma within the National Cancer Data Base undergoing surgery between 2006-2012 were analyzed. Patients were grouped by type of neoadjuvant therapy received: no therapy, chemotherapy only, radiotherapy only, or concomitant chemoradiation. Multivariable modeling was used to compare perioperative outcomes and overall survival between groups. Results: Among 32,978 patients included, 9,714 (29.5%) received no neoadjuvant therapy, 890 (2.7%) chemotherapy only, 1,170 (3.5%) radiotherapy only, and 21,204 (64.3%) concomitant chemoradiation. 5-year overall survival among groups was 62%, 69%, 71%, and 74%, respectively. Compared to no therapy, chemotherapy or radiotherapy alone was not associated with any differences in perioperative or oncologic outcomes (all p > 0.05). With adjustment for patient and disease characteristics, neoadjuvant chemoradiation was associated with a lower likelihood of margin positivity (OR 0.74, p < 0.001), need for permanent colostomy (OR 0.77, 95% CI 0.70-0.85, p < 0.001), 30-day mortality (OR 0.67, p = 0.003), and overall survival (HR 0.69, p < 0.001). When compared to chemotherapy or radiotherapy alone, neoadjuvant chemoradiation was still associated with improved overall survival (vs. chemotherapy: HR 0.83, p = 0.04; vs. radiotherapy: HR 0.75, p < 0.001). Conclusions: Neoadjuvant chemoradiation, not chemotherapy or radiotherapy alone, is important for sphincter-preservation and survival for patients with locally advanced rectal cancer. Despite this finding, one third of patients with locally advanced rectal cancer are failing to receive this therapy in the United States.

Ampulla of Vater carcinomas are rare malignancies that have been traditionally treated with radical surgical resection. Given the mortality associated with pancreaticoduodenectomy, some patients may benefit from local resection. A single-institution outcomes analysis was performed to define the role of local resection.Patients undergoing local resection (ampullectomy) for ampullary carcinomas at Duke University between 1976 and 2010 were analyzed retrospectively. Time-to-event analysis was conducted analyzing all patients undergoing surgery, with and without adjuvant chemoradiation therapy (CRT). Overall survival (OS), local control (LC), metastases-free survival (MFS), and disease-free survival (DFS) were studied using Kaplan-Meier analysis.A total of 17 patients with invasive carcinoma underwent ampullectomy. The 3-and 5-year LC, MFS, DFS and OS rates were 36% and 24%, 68% and 54%, 31% and 21%, and 35% and 21%, respectively. Patients receiving adjuvant CRT did not appear to have improved outcomes compared with surgery alone, although this group tended to have poorer histological grade, more advanced tumor staging and involved surgical margins.Ampullectomy for invasive ampullary adenocarcinomas is a safe procedure but does not offer satisfactory long-term results, mostly due to high local failure rates. Adjuvant CRT therapy does not appear to offer increased local control or survival benefit following ampullectomy, although these results may suffer from selection bias and small sample size. Local resection should be limited to benign ampullary lesions or patients with very small, early tumors with favorable histologic features where radical resection is not feasible.