Nodal Coverage Research Articles

Pretreatment diffusion weighted imaging for clinical outcome assessment in patients undergoing definitive chemoradiation for pancreatic adenocarcinoma.

432 Background: Factors predicting patterns of failure for pancreatic ductal adenocarcinoma (PDA) are not well-established. Diffusion-weighted MRI (DWI) is useful in predicting recurrence for other gastrointestinal malignancies. The purpose of this study was to evaluate for correlation between tumor DWI parameters and clinical outcomes following chemoradiotherapy (CRT) for pancreatic adenocarcinoma. Methods: From 2009 to 2013, 27 patients with locally advanced (n=14), borderline resectable (n=12) or resectable (n=1) PDA underwent CRT. All patients received upfront FOLFIRINOX or gemcitabine-based chemotherapy prior to CRT, and gemcitabine (median weekly dose 800 mg/m2) concurrent with radiotherapy. DWI was obtained during radiotherapy treatment planning, and apparent diffusion coefficient (ADC) maps were generated to allow determination of median tumor ADC. Tumor-directed CRT was administered with respiratory gated intensity modulated radiation therapy, 55Gy in 25 fractions without elective nodal coverage. Patients were followed by imaging every 2-3 months. Log rank test was used to estimate an optimal ADC cut-point of 1.4*10-3mm2/sec based on distant metastasis free survival (DMFS) and overall survival (OS). Analysis of local recurrence was not performed due to limited events. The log-rank test was used to evaluate differences in outcome between groups based on ADC classification. Results: The median time to last follow-up from completion of CRT was 9.7 months for all patients and 11 months among living patients. 5 patients underwent resection following CRT. The 1-year DMFS for patients with median ADC<1.4*10-3mm2/sec was 79.5 percent, compared to 47.6 percent for those with median ADC >1.4. The 1-year OS for patients with median ADC<1.4 was 100 percent, compared to 46.3 percent for those with median ADC >1.4. Both DMFS (p=.041) and OS (p=.003) were significantly improved on log-rank test for ADC<1.4 compared to ADC>1.4. Conclusions: A correlation was observed between DWI parameters and clinical outcomes for PDA. Further prospective study should be explored to validate DWI as a prognostic imaging biomarker.

A Novel Approach to Postmastectomy Radiation Therapy Using Scanned Proton Beams

Postmastectomy radiation therapy (PMRT), currently offered at Massachusetts General Hospital, uses proton pencil beam scanning (PBS) with intensity modulation, achieving complete target coverage of the chest wall and all nodal regions and reduced dose to the cardiac structures. This work presents the current methodology for such treatment and the ongoing effort for its improvements. A single PBS field is optimized to ensure appropriate target coverage and heart/lung sparing, using an in-house-developed proton planning system with the capability of multicriteria optimization. The dose to the chest wall skin is controlled as a separate objective in the optimization. Surface imaging is used for setup because it is a suitable surrogate for superficial target volumes. In order to minimize the effect of beam range uncertainties, the relative proton stopping power ratio of the material in breast implants was determined through separate measurements. Phantom measurements were also made to validate the accuracy of skin dose calculation in the treatment planning system. Additionally, the treatment planning robustness was evaluated relative to setup perturbations and patient breathing motion. PBS PMRT planning resulted in appropriate target coverage and organ sparing, comparable to treatments by passive scattering (PS) beams but much improved in nodal coverage and cardiac sparing compared to conventional treatments by photon/electron beams. The overall treatment time was much shorter than PS and also shorter than conventional photon/electron treatment. The accuracy of the skin dose calculation by the planning system was within ±2%. The treatment was shown to be adequately robust relative to both setup uncertainties and patient breathing motion, resulting in clinically satisfying dose distributions. More than 25 PMRT patients have been successfully treated at Massachusetts General Hospital by using single-PBS fields. The methodology and robustness of both the setup and the treatment have been discussed.

Virtual lymph node analysis to evaluate axillary lymph node coverage provided by tangential breast irradiation.

PurposeTo investigate the coverage of axillary lymph node with tangential breast irradiation fields by using virtual lymph node (LN) analysis.Materials and MethodsForty-eight women who were treated with whole breast irradiation after breast-conserving surgery were analyzed. The axillary and breast volumes were delineated according to the Radiation Therapy Oncology Group (RTOG) contouring atlas. To generate virtual LN contours, preoperative fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans with identifiable LN were fused with the CT scans, and the virtual LN contour were delineated on the CT.ResultsThe median level I and II axillary volume coverage percentages at the VD95% line were 33.5% (range, 5.3% to 90.4%) and 0.6% (range, 0.0% to 14.6%), respectively. Thirty-one LNs in 18 patients were delineated (26 in level I and 5 in level II). In the level I axilla, 84.6% of virtual LNs were encompassed by the 95% isodose line. In the level II axilla, by contrast, none of the virtual LNs were encompassed by the 95% isodose volumes. There was a substantial discrepancy between the RTOG contouring atlas-based axillary volume analysis and the virtual LN analysis, especially for the level I axillary coverage. The axillary volume coverage was associated with the body mass index (BMI) and breast volume.ConclusionThe tangential breast irradiation did not deliver adequate therapeutic doses to the axillary region, particularly those in the level II axilla. Patients with small breast volumes or lower BMI showed reduced axillary coverage from the tangential breast fields. For axillary LN irradiation, individualized anatomy-based radiation fields for patients would be necessary.

Combined photon-electron beams in the treatment of the supraclavicular lymph nodes in breast cancer: A novel technique that achieves adequate coverage while reducing lung dose

Radiation pneumonitis is a well-documented side effect of radiation therapy for breast cancer. The purpose of this study was to compare combined photon-electron, photon-only, and electron-only plans in the radiation treatment of the supraclavicular lymph nodes. In total, 13 patients requiring chest wall and supraclavicular nodal irradiation were planned retrospectively using combined photon-electron, photon-only, and electron-only supraclavicular beams. A dose of 50Gy over 25 fractions was prescribed. Chest wall irradiation parameters were fixed for all plans. The goal of this planning effort was to cover 95% of the supraclavicular clinical target volume (CTV) with 95% of the prescribed dose and to minimize the volume receiving ≥ 105% of the dose. Comparative end points were supraclavicular CTV coverage (volume covered by the 95% isodose line), hotspot volume, maximum radiation dose, contralateral breast dose, mean total lung dose, total lung volume percentage receiving at least 20Gy (V20Gy), heart volume percentage receiving at least 25Gy (V25Gy). Electron and photon energies ranged from 8 to 18MeV and 4 to 6MV, respectively. The ratio of photon-to-electron fractions in combined beams ranged from 5:20 to 15:10. Supraclavicular nodal coverage was highest in photon-only (mean = 96.2 ± 3.5%) followed closely by combined photon-electron (mean = 94.2 ± 2.5%) and lowest in electron-only plans (mean = 81.7 ± 14.8%, p < 0.001). The volume of tissue receiving ≥ 105% of the prescription dose was higher in the electron-only (mean = 69.7 ± 56.1cm3) as opposed to combined photon-electron (mean = 50.8 ± 40.9cm3) and photon-only beams (mean = 32.2 ± 28.1cm3, p = 0.114). Heart V25Gy was not statistically different among the plans (p = 0.999). Total lung V20Gy was lowest in electron-only (mean = 10.9 ± 2.3%) followed by combined photon-electron (mean = 13.8 ± 2.3%) and highest in photon-only plans (mean = 16.2 ± 3%, p < 0.001). As expected, photon-only plans demonstrated the highest target coverage and total lung V20Gy. The superiority of electron-only beams, in terms of decreasing lung dose, is set back by the dosimetric hotspots associated with such plans. Combined photon-electron treatment is a feasible technique for supraclavicular nodal irradiation and results in adequate target coverage, acceptable dosimetric hotspot volume, and slightly reduced lung dose.

SU‐F‐BRF‐07: Impact of Different Patient Setup Strategies in Adaptive Radiation Therapy with Simultaneous Integrated Volume‐Adapted Boost of NSCLC

Purpose:To evaluate the potential impact of several setup error correction strategies on a proposed image‐guided adaptive radiotherapy strategy for locally advanced lung cancer.Methods:Daily 4D cone‐beam CT and weekly 4D fan‐beam CT images were acquired from 9 lung cancer patients undergoing concurrent chemoradiation therapy. Initial planning CT was deformably registered to daily CBCT images to generate synthetic treatment courses. An adaptive radiation therapy course was simulated using the weekly CT images with replanning twice and a hypofractionated, simultaneous integrated boost to a total dose of 66 Gy to the original PTV and either a 66 Gy (no boost) or 82 Gy (boost) dose to the boost PTV (ITV + 3mm) in 33 fractions with IMRT or VMAT. Lymph nodes (LN) were not boosted (prescribed to 66 Gy in both plans). Synthetic images were rigidly, bony (BN) or tumor and carina (TC), registered to the corresponding plan CT, dose was computed on these from adaptive replans (PLAN) and deformably accumulated back to the original planning CT. Cumulative D98% of CTV of PT (ITV for 82Gy) and LN, and normal tissue dose changes were analyzed.Results:Two patients were removed from the study due to large registration errors. For the remaining 7 patients, D98% for CTV‐PT (ITV‐PT for 82 Gy) and CTV‐LN was within 1 Gy of PLAN for both 66 Gy and 82 Gy plans with both setup techniques. Overall, TC based setup provided better results, especially for LN coverage (p = 0.1 for 66Gy plan and p = 0.2 for 82 Gy plan, comparison of BN and TC), though not significant. Normal tissue dose constraints violated for some patients if constraint was barely achieved in PLAN.Conclusion:The hypofractionated adaptive strategy appears to be deliverable with soft tissue alignment for the evaluated margins and planning parameters.Research was supported by NIH P01CA116602

SU‐E‐J‐179: Prediction of Pelvic Nodal Coverage Using Mutual Information Between Cone‐Beam and Planning CTs

Purpose:To investigate if pelvic nodal coverage for prostate patients undergoing intensity modulated radiotherapy (IMRT) can be predicted using mutual image information computed between planning and cone‐beam CTs (CBCTs).Methods:Four patients with high‐risk prostate adenocarcinoma were treated with IMRT on a Varian TrueBeam. Plans were designed such that 95% of the nodal planning target volume (PTV) received the prescription dose of 45 Gy (N=1) or 50.4 Gy (N=3). Weekly CBCTs (N=25) were acquired and the nodal clinical target volumes and organs at risk were contoured by a physician. The percent nodal volume receiving prescription dose was recorded as a ground truth. Using the recorded shifts performed by the radiation therapists at the time of image acquisition, CBCTs were aligned with the planning kVCT. Mutual image information (MI) was calculated between the CBCT and the aligned planning CT within the contour of the nodal PTV. Due to variable CBCT fields‐of‐view, CBCT images covering less than 90% of the nodal volume were excluded from the analysis, resulting in the removal of eight CBCTs.Results:A correlation coefficient of 0.40 was observed between the MI metric and the percent of the nodal target volume receiving the prescription dose. One patient's CBCTs had clear outliers from the rest of the patients. Upon further investigation, we discovered image artifacts that were present only in that patient's images. When those four images were excluded, the correlation improved to 0.81.Conclusion:This pilot study shows the potential of predicting pelvic nodal dosimetry by computing the mutual image information between planning CTs and patient setup CBCTs. Importantly, this technique does not involve manual or automatic contouring of the CBCT images. Additional patients and more robust exclusion criteria will help validate our findings.

Intensity-modulated radiotherapy (IMRT) to prostate and pelvic nodes-is pelvic lymph node coverage adequate with fiducial-based image-guided radiotherapy?

There remains concern regarding the use of fiducial-based image-guided radiotherapy (IGRT) in patients with high-risk prostate cancer also undergoing intensity-modulated radiotherapy (IMRT) to pelvic nodes. By a retrospective study, we aim to ascertain the impact of the use of fiducial-based IGRT on lymph node planned target volume (PTV) coverage. 30 consecutive IMRT prostate and pelvic node plans were reviewed, and dose was recalculated with 1-mm increment movements in anterior, posterior, superior, inferior, right and left directions up to 10 mm. All patients were treated with a full bladder after drinking 450-750 ml of water and empty rectum with the use of sodium citrate enemas daily. Dose-volume histogram parameters were recorded at each position, specifically nodal PTV V95%, V99% and V100%. A local IGRT database was used to identify the likelihood of a particular bony to fiducial offset in all directions. The combined data were used to calculate the percentage risk of underdosing the lymph node PTV on any given fraction. The likelihood of an offset in the left, right and anterior directions occurring and resulting in a failure to cover the PTV was <0.25%. The likelihood of a posterior offset occurring and resulting in inadequate coverage was slightly higher but remained <1%. This study confirms the safety of fiducial-based image-guided IMRT (IG-IMRT) with a strict bowel and bladder protocol, allowing a reduction of the clinical target volume to PTV margin of the prostate volume and consequent reduction in rectal toxicity. This study strengthens the evidence supporting the safe implementation of fiducial-based IG-IMRT treating the prostate and pelvic nodes in high-risk prostate cancer.

Reduction in Radiation Therapy Volumes for Patients With Head and Neck Squamous Cell Carcinoma Improves Patient-Reported Quality of Life

At our institution, we began utilizing IMRT in 1997 for Head and Neck Squamous Cell Carcinoma (HNSCC). Three successive contouring guideline generations have been developed with the goal of reducing radiation therapy volumes and improving quality of life (QOL) while maintaining locoregional control. We previously reported no failures in the regions spared of radiation therapy. Here we present patient reported quality of life measures after reduction in radiation therapy volumes. Primary sites included were oral cavity, oropharynx, hypopharynx, larynx and unknown primary HNSCC. Generation 1 (G1; 1997-2004) contouring guidelines included comprehensive bilateral (BL) nodal irradiation with an AP low neck match field and BL parotid sparing. Generation 2 (2004-2007) guidelines eliminated coverage of the clinically N0 (cN0) contralateral level IIB nodal station. Generation 3 (G3; 2007-2010) eliminated both the cN0 contralateral level IIB lymph nodes and the cN0 contralateral retropharyngeal lymph nodes (RPLNs). Specifically, high level II nodal coverage in the N0 side of the neck was contoured only up to the level were the posterior belly of the digastric crosses the internal jugular vein, and RPLNs in the cN0 side of the neck were excluded. In addition, for patients with N0 disease involving the oral cavity or larynx, BL RPLN and level IIb nodes were spared. The previously validated 20 question MD Anderson Dysphagia Inventory was used to collect patient reported QOL data. Wilcoxon rank sum test was used to test the significance between G1 and G3 regarding emotional, physical, functional and global QOL domains. These were scaled from 0 to 100 with 0 being the worst QOL and 100 the best QOL. Fisher exact test was used to test for association between clinical variables and generation. Long-term outcome data was analyzed for 44 patients from G1 and 51 patients from G3 with mean time from therapy to completion of questionnaire of 5 years for G1 and 3 years for G3. More patients in G3 received chemotherapy as compared to G1 (78% vs 39%), otherwise there were no significant differences between groups with regards to primary tumor site, primary vs postoperative therapy, T, N, and overall stage groupings. Mean Global QOL for G1 was 34.1 and for G3 was 66.7 (p < 0.001). QOL was significantly improved in the emotional, physical and functional domains for patients in G3 compared to G1 (p < 0.005). Patients treated with the most recent contouring guideline generation, which eliminates the cN0 contralateral level IIB and RPLNs, reported significantly improved QOL compared to patients treated with comprehensive elective nodal irradiation.

Proton therapy may allow for comprehensive elective nodal coverage for patients receiving neoadjuvant radiotherapy for localized pancreatic head cancers.

Neoadjuvant radiotherapy has the potential to improve local disease control for patients with localized pancreatic cancers. Concern about an increased risk of surgical complications due to small bowel and gastric exposure, however, has limited enthusiasm for this approach. Dosimetric studies have demonstrated the potential for proton therapy to reduce intestinal exposure compared with X-ray-based therapy. We sought to determine if neoadjuvant proton therapy allowed for field expansions to cover high-risk nodal stations in addition to the primary tumor. Twelve consecutive patients with nonmetastatic cancers of the pancreatic head underwent proton-based planning for neoadjuvant radiotherapy. Gross tumor volume was contoured using diagnostic computed tomography (CT) scans with oral and intravenous contrast. Four-dimensional planning scans were utilized to define an internal clinical target volume (ICTV). Five-mm planning target volume (PTV) expansions on the ICTV were generated to establish an initial PTV (PTV1). A second PTV was created using the initial PTV but was expanded to include the high-risk nodal targets as defined by the RTOG contouring atlas (PTV2). Optimized proton plans were generated for both PTVs for each patient. All PTVs received a dose of 50.4 cobalt gray equivalent (CGE). Normal-tissue exposures to the small bowel space, stomach, right kidney, left kidney and liver were recorded. Point spinal cord dose was limited to 45 CGE. Median PTV1 volume was 308.75 cm(3) (range, 133.33-495.61 cm(3)). Median PTV2 volume was 541.75 cm(3) (range, 399.44-691.14 cm(3)). In spite of the substantial enlargement of the PTV when high-risk lymph nodes were included in the treatment volume, normal-tissue exposures (stomach, bowel space, liver, and kidneys) were only minimally increased relative to the exposures seen when only the gross tumor target was treated. Proton therapy appears to allow for field expansions to cover high-risk lymph nodes without significantly increasing critical normal-tissue exposure in the neoadjuvant setting.

SU-E-P-09: Feasibility of Axillary Target Coverage Utilizing High Tangent Prone Breast Radiation

Purpose: To evaluate the ability to treat level I and level II axillary lymph nodes utilizing a high tangent prone breast radiotherapy technique. Methods: Twenty-one patients were treated with whole breast radiation utilizing a prone technique. Retrospectively, axillary nodes were contoured as levels I and low lying level II with the intent of elective nodal coverage. Treatment plans were designed as tangential fields with the superior border set to cover the contoured axillary volume (high tangents). Dose-volume histograms (DVH) were evaluated for axillary, breast, lung and heart (for left breast treatments) coverage. The percent volume receiving greater than or equal to 95% of the prescribed dose (V95) was obtained for the breast and axillary regions. Results: The 95% isodose line encompassed on average 98.0% of breast volumes (range, 93.2 to 100.0%). The mean V95 for the level I and level II axillary regions were 99.5% (range, 98.3 to 100.0%) and 97.4% (range, 92.5 to 100.0%), respectively. The mean percent volume of the ipsilateral lung receiving greater than 20 Gy was 7.7% (range, 4.0 to 13.4%), and the percent volume of the heart receiving greater than 40 Gy was 0.57% (range, 0 to 2.1%). Conclusion: These results imply that prone breast radiation with high tangents is an effective and safe technique for the treatment of level I and level II axilla in addition to breast volumes. With increasing trends to limit axillary dissections in sentinel node positive patients, radiotherapy techniques to adequately cover nodal volumes has become more important. With historic data that suggested lower coverage in a prone position, we present techniques to adequately cover elective nodal volumes with good success.

Proton Therapy May Allow Elective Nodal Coverage in the Setting of Neoadjuvant Radiation Therapy for Pancreatic Head Cancers Without Significantly Increasing Normal Tissue Exposure

Neoadjuvant radiation therapy has the potential to improve local disease control and cure rates for patients with localized pancreatic head cancers. Concern about an increased risk of surgical complications due to small bowel and gastric exposure however has limited the enthusiasm for this approach among many surgeons. Dosimetric studies have demonstrated the potential for proton therapy to reduce intestinal exposure compared with x-ray based therapy. The current study attempts to determine if proton therapy may further allow for field expansions to cover high-risk nodal stations in the setting of neoadjuvant radiation therapy.

Intensity Modulated Radiation Therapy and Level 1B Nodal Coverage for Oropharyngeal Carcinoma

The rate of pathologic level IB lymph node involvement in clinically node negative oropharyngeal cancer is very low, ranging from 0 to 3%. It is controversial whether or not this nodal level should be included in intensity modulated radiation therapy (IMRT) plans. Common practice is to irradiate at least the ipsilateral IB level. However, elective irradiation of level IB increases dose to the larynx, oral cavity, and mandible, potentially increasing acute and long-term toxicity. This study reports regional control rates and long-term toxicity for employing a policy of withholding radiation to the level IB lymph nodes unless clinically indicated.

Kinomic Profiling Identifies Pathways of HER2 Targeted Therapy Resistance in HER2 Positive Breast Cancer Cell Lines

Common practice is to irradiate at least the ipsilateral IB level. However, elective irradiation of level IB increases dose to the larynx, oral cavity, and mandible, potentially increasing acute and long-term toxicity. This study reports regional control rates and long-term toxicity for employing a policy of withholding radiation to the level IB lymph nodes unless clinically indicated. Materials/Methods: Between 2003 and 2010, 95 patients with stage I IVB oropharyngeal cancer were treated with definitive IMRT with simultaneous-integrated boost technique. The median age was 59. The T and N stage distributions were: 28% T1, 40% T2, 22% T3, 10% T4, 9% N0, 15% N1, 16% N2a, 35% N2b, 11% N2c, and 14% N3. The primary sites were tonsil (52%), base of tongue (45%), and others (3%). Of 55 patients with HPV data, 89% were positive. Median dose to the gross tumor volume was 70 Gy. Ninety-four percent of patients had concurrent chemotherapy, and 12% had pre-radiation (RT) neck dissection. Indications for ipsilateral IB nodal coverage were: (1) a grossly enlarged level IB node, (2) primary or nodal tumor invasion of the ipsilateral level IB or submandibular gland (SMG), and (3) tumor involvement of the oral cavity or other structures that drain primarily to the ipsilateral level IB. Contralateral IB level was not covered in the absence of the above clinical factors in the contralateral neck. Adverse late effects were determined using the Common Terminology Criteria Adverse Event (CTCAE) v4.03. Results: Of 82 patients that did not have a pre-RT neck dissection, 28% (23/82) had ipsilateral level IB coverage and 1 had bilateral IB coverage. Of 23 patients with ipsilateral IB coverage, 13 were for SMG involvement, 5 for IB node involvement, 2 for oral cavity involvement, 2 for oral cavity +/SMG +/IB node involvement, and 1 for unknown reasons due to incomplete data. Of 11 patients that had a pre-RT neck dissection, none had the contralateral IB level covered. With a median follow-up of 2.7 years, only one patient failed in the neck (in the tracheostomy stoma site) at 11.3 months. At 2 years, regional control, local control, disease-free survival and overall survival were 99%, 99%, 89%, and 94%, respectively. No patients developed grade 3 xerostomia or grade 4 osteonecrosis. At 2 years, rates of grade 1-2 xerostomia, gastrostomy tube dependency, and grade 3 osteoradionecrosis were 15%, 4%, and 1%, respectively. Conclusions: Our data supports that in the absence of level IB and oral cavity involvement, the ipsilateral and the contralateral level IB nodal levels do not need to be covered in IMRT plans for oropharyngeal carcinoma. Author Disclosure: J.W. Jang: None. R.J. Parambi: None. L.S. Liliana: None. N.J. Liebsch: None. A.W. Chan: None.

Axillary lymph node coverage of tangent radiotherapy: Comparison of supine versus prone positioning.

200 Background: Recent randomized evidence has demonstrated low rates of axillary nodal failure in patients with one to two positive lymph nodes who receive local therapy with sentinel lymph node biopsy and simple tangential radiotherapy alone. Decreasing utilization of complete axillary nodal dissections has potential implications for radiotherapy treatment delivery design. We sought to compare the inadvertent coverage of the axillary lymph nodal regions between supine versus prone position for whole breast radiotherapy using simple tangent fields. Methods: Twenty patients with breast cancer who had previously received whole breast radiotherapy with simple tangent fields were randomly selected. Patients were selected such that 10 patients had received treatment in the supine position and 10 patients in the prone position. Axillary lymph node levels I-III were contoured by a single physician according to the RTOG breast contouring atlas. The previously generated radiotherapy plans, each to deliver a prescribed dose between 42.56 and 50Gy, were dosimetrically compared to assess differences in coverage of the nodal volumes. Results: In both positions, dose to each of the axillary nodal regions was low. For level I, the volume receiving 95% of the prescribed dose (V95) was 34.7% for supine positioning and 1.6% for prone positioning. All other analyzed volumes, specifically V25 (71.5% vs 32.6%), V50 (63.3% vs 28.2%), and V75 (57.6% vs 24.1%), were 50% greater for supine compared to prone positioning. Level II coverage was less with V95 of 6% and 0.1% respectively. Similarly V25 (32.8% vs 5.7%), V50 (25.7% vs 3.8%), and V75 (20.3% vs 2.1%) were less compared to level one and greater in the supine position. Level III coverage was less than 10% for both positions at all measured volumes of V95, V75, V50, and V25. Conclusions: Delivery of radiotherapy using simple tangents inadequately covers all axillary nodal levels. Coverage is greater in the supine position with very little inadvertent coverage in the prone position. The risk of nodal recurrence should be carefully considered when deciding to use a simple tangential field design. Additional factors such as dose to the lung and heart should also be considered for positioning.

A protocol to extend the longitudinal coverage of on‐board cone‐beam CT

The longitudinal coverage of a LINAC‐mounted CBCT scan is limited to the corresponding dimensional limits of its flat panel detector, which is often shorter than the length of the treatment field. These limits become apparent when fields are designed to encompass wide regions, as when providing nodal coverage. Therefore, we developed a novel protocol to acquire double orbit CBCT images using a commercial system, and combine the images to extend the longitudinal coverage for image‐guided adaptive radiotherapy (IGART). The protocol acquires two CBCT scans with a couch shift similar to the “step‐and‐shoot” cine CT acquisition, allowing a small longitudinal overlap of the two reconstructed volumes. An in‐house DICOM reading/writing software was developed to combine the two image sets into one. Three different approaches were explored to handle the possible misalignment between the two image subsets: simple stacking, averaging the overlapped volumes, and a 3D‐3D image registration with the three translational degrees of freedom. Using thermoluminescent dosimeters and custom‐designed holders for a CTDI phantom set, dose measurements were carried out to assess the resultant imaging dose of the technique and its geometric distribution. Deformable registration was tested on patient images generated with the double‐orbit protocol, using both the planning FBCT and the artificially deformed CBCT as source images. The protocol was validated on phantoms and has been employed clinically for IRB‐approved IGART studies for head and neck and prostate cancer patients.PACS number: 87.57.nj

Phase I/II study of preoperative (pre-op) short course chemoradiation (CRT) with proton beam therapy (PBT) and capecitabine (cape) followed by early surgery for resectable pancreatic ductal adenocarcinoma (PDAC) of the head.

4021 Background: Standard adjuvant 6 week CRT may delay and reduce tolerability of adjuvant gemcitabine-based chemotherapy. We explore the safety and efficacy of a one-week course of pre-op CRT with PBT and cape followed by early pancreaticoduodenectomy (PD). Methods: Patients with radiographically resectable, biopsy-proven PDAC of the head were enrolled from May 2007-December 2010 on this prospective, NCI-sponsored clinical trial. Eligibility included no CT involvement of SMA or celiac artery; No metastatic disease. Dose level 1 consisted of PBT delivered 3 Gy x 10. Pts in subsequent dose levels received 5 Gy x 5 in progressively shortened schedules: level 2 (wk 1 M W F, wk 2 T Th), level 3 (wk 1 M T Th F, wk 2 M), level 4 (wk 1 M-F). PBT was targeted at pancreatic mass with elective nodal coverage. Pts received Cape 825 mg/m2 BID wk 1 and 2 M-F. Surgery was performed 1-6 wks after completion of cape. Patients were recommended to receive 6 mo of gemcitabine after surgery. Genotyping of 15 genes (including KRAS, PIK3CA, BRAF, NRAS, TP53, IDH1) was performed. Results: 50 pts were enrolled on study. 48 patients are eligible for this analysis. 3 pts were treated at each of dose levels 1-3. 6 pts were at dose level 4, which was selected as MTD. No DLTs were observed. 35 patients were treated in the phase II portion at the MTD. Gr 3 toxicity was noted in 2 pts (chest wall pain-1, colitis-1). 38 pts underwent PD. Reasons for no PD were: metastatic disease-9, unresectable tumor-1. Mean post-op length of stay was 7 days (range 5-47). 6/38 (16%) resected pts had positive margins. 28/38 (74%) had positive nodes. Median follow up is 21 months among the 19 patients still alive. 4/48 (8%) local failures in ALL patients. mOS and mPFS are 18 and 10 months respectively for ALL patients and 27 and 14 months for RESECTED patients. Of 28 patients with genotype data available, 22 (79%) had KRAS mutations. 10/22 KRAS mt and 4/6 KRAS wt pts are alive. Conclusions: Pre-op CRT with 1 wk of PBT and capecitabine followed by early surgery is well tolerated and associated with favorable local control. Complete genotype and DPC4 data will be presented at the meeting.

Celiac Node Failure Patterns After Definitive Chemoradiation for Esophageal Cancer in the Modern Era

The celiac lymph node axis acts as a gateway for metastatic systemic spread. The need for prophylactic celiac nodal coverage in chemoradiation therapy for esophageal cancer is controversial. Given the improved ability to evaluate lymph node status before treatment via positron emission tomography (PET) and endoscopic ultrasound, we hypothesized that prophylactic celiac node irradiation may not be needed for patients with localized esophageal carcinoma. We reviewed the radiation treatment volumes for 131 patients who underwent definitive chemoradiation for esophageal cancer. Patients with celiac lymph node involvement at baseline were excluded. Median radiation dose was 50.4 Gy. The location of all celiac node failures was compared with the radiation treatment plan to determine whether the failures occurred within or outside the radiation treatment field. At a median follow-up time of 52.6 months (95% CI 46.1-56.7 months), 6 of 60 patients (10%) without celiac node coverage had celiac nodal failure; in 5 of these patients, the failures represented the first site of recurrence. Of the 71 patients who had celiac coverage, only 5 patients (7%) had celiac region relapse. In multivariate analyses, having a pretreatment-to-post-treatment change in standardized uptake value on PET >52% (odds ratio [OR] 0.198, p = 0.0327) and having failure in the clinical target volume (OR 10.72, p = 0.001) were associated with risk of celiac region relapse. Of those without celiac coverage, the 6 patients that later developed celiac failure had a worse median overall survival time compared with the other 54 patients who did not fail (median overall survival time: 16.5 months vs. 31.5 months, p = 0.041). Acute and late toxicities were similar in both groups. Although celiac lymph node failures occur in approximately 1 of 10 patients, the lack of effective salvage treatments and subsequent low morbidity may justify prophylactic treatment in distal esophageal cancer patients.

Contouring inguinal and femoral nodes; how much margin is needed around the vessels?

PurposeTo determine the optimal margin needed around the femoral vessels for appropriate inguinofemoral lymph node coverage and to propose guidelines defined by anatomic boundaries for clinical target volume delineation. Methods and MaterialsTwenty-two patients with pelvic malignancies and involved inguinal lymph nodes treated with conformal radiation therapy were selected. Lymph nodes were considered positive if they were pathologically malignant by biopsy, had 18F-fluorodeoxyglucose avidity on positron emission tomography or measured ≥1.5 cm on computed tomographic scan. We measured distance from the center of node(s) to the edge of the nearest femoral vessel. ResultsThere were 52 total positive inguinal nodes among 22 patients. Relative to the femoral vessels, the location of the nodes were 51.9% anteromedial, 21.2% anterior, 11.5% anterolateral, 9.6% medial, 1.9% posterior, and 3.9% lateral. To cover ≥90% disease, the margins needed around the nearest femoral vessel were anteromedial ≥35 mm, anterior ≥23 mm, anterolateral ≥25 mm, medial ≥22 mm, posterior ≥9 mm, and ≥32 mm lateral. The corresponding anatomic boundaries were the following: laterally, medial border of the iliopsoas; medially, lateral border of adductor longus or medial end of pectineus; posteriorly, iliopsoas muscle laterally and anterior aspect of the pectineus muscle; medially and anteriorly, the anterior edge of the sartorius muscle. Most of the macroscopic nodes were medial or anteromedial to the femoral vessels. No patient had involved posterior or lateral nodes alone without positive nodes in the anterior or anteromedial positions. ConclusionsCircumferential margins around femoral vessels required to adequately cover this nodal region were >2 cm in most directions. Contouring the inguinal lymph nodes as a compartment defined by the anatomic landmarks suggested above may be more reproducible. Physicians should exercise caution in extrapolating pelvic nodal contouring guidelines to inguinal lymph nodal contouring.

Helical tomotherapy and concurrent gemcitabine-based chemotherapy for locally advanced pancreatic cancer.

318 Background: To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed. Methods: We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8-59.9 Gy) and concomitant chemotherapy between May 2006 and May 2009. Radiotherapy was directed to the primary tumor with a 0.5 cm margin without prophylactic nodal coverage. Twenty nine patients (79%) received full-dose (1000 mg/m2) gemcitabine based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%). Results: The median follow-up was 15.5 months (range 3.4-43.9) for the entire cohort, and 22.5 months (range 12.0-43.9) for surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (20%) were converted to resectable status, including one with a pathologic complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than grade 3. Severe late GI toxicity (≥ Grade 3) occurred in 10 patients (26%); one treatment related death due to GI bleeding was observed. Conclusions: High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity.

High-dose Helical Tomotherapy With Concurrent Full-dose Chemotherapy for Locally Advanced Pancreatic Cancer

To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high-dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed. We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8-59.9 Gy) and concomitant chemotherapy between 2006 and 2009. Radiotherapy was directed to the primary tumor with a 0.5-cm margin without prophylactic nodal coverage. Twenty-nine patients (79%) received full-dose (1000 mg/m(2)) gemcitabine-based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%). The median follow-up was 15.5 months (range, 3.4-43.9) for the entire cohort, and 22.5 months (range, 12.0-43.9) for the surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (21%) were converted to resectable status, including 1 with a pathological complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than Grade 3. Severe late GI toxicity (≥ Grade 3) occurred in 10 patients (26%); 1 treatment-related death from GI bleeding was observed. High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity.