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We report long-term outcomes from our phase 1 dose-escalation study to determine the maximum tolerated dose of single-fraction liver SABR pooled with our subsequent single institutional experience with patients treated postprotocol at the highest dose level (40 Gy) established from the phase 1 study.Patients with liver metastases from solid tumors located outside of the central liver zone were treated with single-fraction SABR on a phase 1 dose escalation trial. At least 700 cc of normal liver had to receive9.1 Gy. Seven patients with 10 liver metastases received the initial prescription dose of 35 Gy, and dose was then escalated to 40 Gy for 7 more patients with 7 liver metastases. An additional 19 postprotocol patients with 22 liver metastases were treated to 40 Gy in a single fraction. Patients were followed for toxicity and underwent serial imaging to assess local control.Median imaging follow-up for the combined cohort (n = 33, 39 lesions) was 25.9 months; 38.9 months for protocol patients and 20.2 months for postprotocol patients. Median lesion size was 2.0 cm (range, 0.5-5.0 cm). There were no dose-limiting toxicities observed for protocol patients, and only 3 grade 2 toxicities were observed in the entire cohort, with no grade ≥3 toxicities attributable to treatment. Four-year actuarial local control of irradiated lesions in the entire cohort was 96.6%, 100% in the protocol group and 92.9% in the subsequent patients. Two-year overall survival for all treated patients was 82.0%.For selected patients with liver metastases, single-fraction SABR at doses of 35 and 40 Gy was safe and well-tolerated, and shows excellent local control with long-term follow-up; results in subsequent patients treated with single-fraction SABR doses of 40 Gy confirmed our earlier results.

Purpose Despite the proliferation of radiation oncology fellowship training programs over the last decade, limited data exist on their actual details. We present findings from a focused survey aiming to evaluate the experiences of fellowship-trained physicians. Methods and Materials A customized 23-item questionnaire was systematically distributed to 127 board-certified or eligible physicians who had completed a radiation oncology fellowship in the United States between 2005 and 2017 and whose contact information was available. The survey queried motivations for pursuing fellowship and aspects of training pertaining to expertise, mentorship, salary, employment outcome, satisfaction, and regret. Results A total of 92 subjects responded. Five were still in fellowship and 3 failed to complete the survey in its entirety, leaving 84 (56 male; 28 female) eligible for analysis. Graduates of US residencies comprised 62% of respondents. The desire to build a career in a particular treatment modality was most commonly cited as the primary motivation for pursuing fellowship (58%), followed by the desire to secure an academic faculty position (16%) and the desire to secure a job in a specific geographic location (14%). Subspecialty fellowships were most often done in proton therapy (27%) and brachytherapy (24%). Among the 26 people who completed proton fellowships, only 10 were currently practicing using protons (38%). The majority of fellows (52%) were compensated between $50,000 and $75,000 annually. Seventy-eight (93%) and 72 (86%) physicians were satisfied with fellowship training and their job after fellowship, respectively. Six of the 52 US graduates (12%) and 0 of the 32 international graduates (0%) reported that they would not recommend fellowship to others. Conclusions The motivations for pursuing radiation oncology fellowships appear to be complex, and variability exists with respect to multiple aspects of training, including those related to satisfaction and employment outcomes.

Purpose/objective(s) Multi-agent chemotherapy and radiation therapy (RT) has increased the proportion of locally advanced pancreatic cancer (LAPC) patients (pts) able to undergo resection and improve overall survival compared to those who are not resected. However, prior data from our institution (2016-2019) indicate that despite an R0 rate of 88%, LF developed in > 30% of LAPC pts resected after neoadjuvant therapy (NAT). This high LF rate is a rationale to explore dose escalation (DE) in the NAT setting, as data highlighting the value of DE have been limited to unresectable disease. Importantly, the optimal method for DE remains unclear. While conformal external beam RT can ablate part of the target, under-coverage in close proximity to the stomach and bowel remains problematic. For pancreatic head tumors, Whipple resection presents an opportunity for subsequent DE with IORT, as the duodenum is resected and direct access to microscopic peri-vascular residual disease is allowed. It also allows for precise DE based on the surgeons' recommendations. Herein, we model DE approaches, comparing pre-operative DE-IMRT with an approach in which a high-dose rate (HDR)-IORT boost is given after SBRT, with a goal biological effective dose (BED10) of 100 Gy. Materials/methods Ten consecutive LAPC pts were modeled with both DE-IMRT to 75 Gy in 25 fractions and SBRT to 40 Gy in 5 fractions followed by HDR-IORT to 15 Gy, using an 192Ir source. Notably, to minimize LF after surgery, our clinical tumor volume (CTV) has been the "Heidelberg Triangle" of tissue between the celiac, superior mesenteric, and common hepatic arteries and portal vein, which contains perineural and lymphatic tissue at risk of harboring subclinical disease. A 5mm planning tumor volume (PTV) expansion was used. A 3mm expansion on stomach and bowel was constrained to 60 Gy and 40 Gy for DE-IMRT and SBRT, respectively. For IORT modeling, the Freiburg Flap was superimposed on the planning CT, and dose was prescribed to the target volume surface. Given rapid dose fall-off with HDR-IORT, SBRT was optimized to compensate for IORT under-coverage, with higher dose allowed posteriorly but with an overall hotspot less than 50 Gy. Descriptive statistics were generated for coverage to target structures. Results With DE-IMRT, mean V75Gy for the CTV and PTV was only 79% +/- 14.4% and 52% +/- 13%, respectively. In comparison, posteriorly optimizing the SBRT plan in anticipation of anterior IORT supplementation improved coverage with ablative BED. For the anterior half of the target volume, HDR-IORT created a dose gradient of 10-15 Gy, whereas for the posterior half of the target volume, HDR-IORT created a dose gradient of 5-10 Gy. Optimizing the SBRT plan to complement this with 40 Gy to the anterior half of the volume and 45 Gy to the posterior half of the volume was feasible with > 90% coverage with BED10 of 100Gy in composite. Conclusion Dose escalation with SBRT/IORT may allow for better target coverage with ablative RT dose as compared to DE-IMRT and should be explored clinically.

PURPOSE/OBJECTIVE(S) To evaluate a novel technique for spatially fractionated (GRID) therapy of bulky tumors using proton pencil beam scanning (PBS) and to compare dosimetry to a photon arc (VMAT) technique. MATERIALS/METHODS PBS and VMAT GRID plans were generated for five patients with bulky tumors. GRID targets were arranged along the long axis of gross tumor, spaced at 2 cm and 3 cm apart, and treated with a prescription of 15 Gy in a single fraction. PBS plans utilized two-beam multiple-field optimization with robustness evaluation. Dosimetric parameters including peak-to-edge ratio (PEDR), ratio of dose to 90% of the valley to dose to 10% of the peak (VPDR (D90/D10)), and volume of normal tissue receiving at least 5 Gy (V5) and 10 Gy (V10) were calculated. RESULTS Gross tumor volume values ranged from 826-1468 cc. PEDR for PBS was higher than for VMAT at 7.2 ± 2.51 versus 2.4 ± 0.61 (2-cm spacing, P = 0.02), and 8.4 ± 2.00 versus 2.8 ± 0.37 (3-cm spacing, P = 0.01), respectively. VPDR (D90/D10) for PBS was lower than for VMAT at 0.034 ± 0.031 versus 0.41 ± 0.12 (2-cm spacing, P = 0.004), and 0.008 ± 0.007 versus 0.33 ± 0.08 (3-cm spacing, P = 0.002), respectively. Normal tissue V5 was lower for PBS than for VMAT at 343.2 cc ± 176.4 cc versus 917.6 cc ± 459.0 cc (2-cm spacing, P = 0.03), and 250.3 cc ± 114.7 cc versus 520.7 cc ± 181.1 cc (3-cm spacing, P = 0.02), respectively. Normal tissue mean dose was lower with PBS than with VMAT at 0.20 Gy ± 0.15 Gy versus 0.92 Gy ± 0.41 Gy (2-cm spacing, P = 0.03), and 0.17 Gy ± 0.11 Gy versus 0.82 Gy ± 0.33 Gy (3-cm spacing, P = 0.02), respectively. CONCLUSION PBS GRID for bulky tumors may result in improved dosimetry when compared to a VMAT approach. This PBS technique may be useful in bulky tumors that have a deep-seated location, complex shape, or adjacent critical organs.

Purpose/Objective(s) The role of radiation for pancreatic cancer remains controversial with heterogeneous clinical response. Characterization of molecular biomarkers that predict radiosensitivity may help select patients for radiation therapy. The purpose of this study was to determine if somatic mutations and mutational frequency are associated with pathologic and survival outcomes in a cohort of patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) who were treated with neoadjuvant chemotherapy and stereotactic body radiotherapy (SBRT) followed by surgical exploration. Materials/Methods Patients treated with neoadjuvant chemotherapy and SBRT followed by surgical exploration from 2017-2019 and who consented to next generation sequencing (NGS) of their primary tumor were included in the study. Tissue samples were obtained with FNA at initial biopsy (n = 5) or from surgical specimen (n = 38). Univariate (UVA) and multivariable analyses (MVA) were performed to determine associations between somatic mutations and variant allele frequency (VAF) with pathologic and survival outcomes. Local response was defined as achieving complete response, marked response, or moderate response on pathology. Results A total of 43 patients underwent NGS of their primary tumor with either solid tumor panel (n = 35) or Foundation One (n = 8). Neoadjuvant therapy consisted of FOLFIRNOX (n = 36) and/or gemcitabine/abraxane (n = 11) followed by SBRT in 33 Gy in 5 fractions (range, 30-36 Gy/5 fractions). Surgical resection was performed in 35/43 patients and aborted in 8/43. Median follow-up time was 20.4 months. Median OS, PFS, DMFS, and LPFS after SBRT were 21.3 months, 9.7 months, 10.0 months, and 22.0 months, respectively. KRAS mutations were observed in 96% (43/45) of patients. On UVA and MVA, tumors with KRAS G12V mutation demonstrated a higher local response rate to neoadjuvant therapy when compared to tumors with other KRAS mutations (100% vs 68.4%, P = 0.003). On UVA and MVA, alterations in NOTCH1/2 and KRAS VAF > 4.3 were associated with worse OS. The median OS for NOTCH1/2 mutated patients was 14.4 months vs 27.5 months in NOTCH1/2 wild type patients (P = 0.045). The median OS for patients with KRAS VAF > 4.3 was 13.8 months vs 31.3 months for patients with KRAS VAF ≤ 4.3 (P = 0.025). KRAS VAF > 4.3 was also associated with worse DMFS (median, not met vs 8.1 months; P = 0.043) and a trend towards significance with worse PFS (median, 8.1 months vs 13.9 months; P = 0.058). Conclusion Tumors with KRAS G12V mutation demonstrated a greater local response in BRPC and LAPC patients treated with neoadjuvant chemotherapy, SBRT, and surgery. Alterations in NOTCH1/2 and KRAS VAF > 4.3 were associated with worse OS. KRAS VAF > 4.3 was also associated with worse DMFS and PFS. As genetic characterization of pancreatic tumors becomes more universal, further investigation into the association between these mutations and radiation-specific response endpoints should be pursued.

PURPOSE/OBJECTIVE(S) Although overshadowed by metastatic failure, patients (pts) with locally advanced pancreatic adenocarcinoma (LAPC) who undergo resection after neoadjuvant therapy (NAT) also experience high rates of locoregional failure (LF). Prior data from our institution indicate LF developed in > 30% of LAPC pts resected after NAT with multi-agent chemotherapy (MA-CT) and RT from 2016-2019 despite an R0 rate of 88%. In this cohort, gross disease and involved vessels were the target, raising the question whether field design modification could reduce LF. Indeed, elective treatment of tissue at risk of harboring microscopic residual disease after resection may be critical, but consensus regarding what constitutes the CTV for NAT does not exist. In the surgical literature, support is growing for extended dissection of the "Heidelberg Triangle" (HT), tissue between the celiac artery (CA), superior mesenteric artery (SMA), common hepatic artery (CHA), and portal vein (PV) that contains key perineural and lymphatic tracts at risk of harboring subclinical disease. Whether this concept can be applied to CTV field design is unclear. In investigation, we mapped LF locations in LAPC pts to assess if the LF distribution matches the anatomy of the Triangle volume (TV). MATERIALS/METHODS A total of 21 consecutive LAPC pts with involvement of the head or neck at diagnosis treated at our institution with MA-CT and stereotactic body radiation who developed LF after resection were reviewed. The TV starts superiorly at the CA take-off point, extends along the CA to the trifurcation, then extends laterally along the CHA and stops at the proximal proper HA. At this lateral boundary, the PV is also included and the TV extends posteriorly to the aorta along the inferior vena cava, including the SMA take-off until the crossing of the left renal vein. From the lateral boundary of the PV, the volume descends to the superior mesenteric vein (SMV) and covers the groove between the SMA-SMV. The inferior boundary is the branching of the first jejunal artery (JA) from the SMA. Descriptive statistics were generated to report the frequency of LF in relation to the TV and the frequency of critical vasculature involvement. RESULTS In 21 consecutive pts, the median TV was 80.2 ± 30.1 cubic centimeters (cc) (27.7-110.3 cc). The LF centroid was located within the TV in 20 pts (95.2%). The SMA from take-off to the JA branch-point was the most common vessel involved at diagnosis (85.7%) and at failure (80.1%) with the next four being the CA (66.7%, 57.1%), SMV (61.9%, 66.7%), CHA (61.9%, 38.1%), and PV (38.1%, 47.6%). CONCLUSION The TV nearly universally encapsulates LF location and could serve as the basis for CTV design in the neoadjuvant setting. Future studies should investigate the feasibility of therapeutic dosimetry to this volume and ultimately whether treatment of the TV reduces LF.

Purpose Renal cell carcinoma is refractory to conventional radiation therapy but responds to higher doses per fraction. However, the dosimetric data and clinical factors affecting local control (LC) are largely unknown. We aimed to evaluate the safety and efficacy of stereotactic ablative radiation therapy (SAbR) for extracranial renal cell carcinoma metastases. Methods and Materials We reviewed 175 metastatic lesions from 84 patients treated with SAbR between 2005 and 2015. LC and toxicity after SAbR were assessed with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Predictors of local failure were analyzed with χ 2 , Kaplan-Meier, and log-rank tests. Results In most cases (74%), SAbR was delivered with total doses of 40 to 60 Gy, 30 to 54 Gy, and 20 to 40 Gy in 5 fractions, 3 fractions, and a single fraction, respectively. The median biologically effective dose (BED) using the universal survival model was 134.5 Gy. The 1-year LC rate after SAbR was 91.2% (95% confidence interval, 84.9%-95.0%; median follow-up, 16.7 months). Local failures were associated with prior radiation therapy (hazard ratio [HR], 10.49; P P =.0189), spinal location (HR, 5.36; P =.0041), previous systemic therapy status (0-1 vs >1; HR, 3.52; P =.0217), and BED P =.0254). Dose received by 99% of the target volume was the strongest dosimetric predictor for LC. Upon multivariate analysis, dose received by 99% of the target volume greater than BED of 98.7 Gy and systemic therapy status remained significant (HR, 0.12 and 3.64, with P =.0014 and P =.0472, respectively). Acute and late grade 3 toxicities attributed to SAbR were observed in 3 patients (1.7%) and 5 patients (2.9%), respectively. Conclusions SAbR demonstrated excellent LC of metastatic renal cell carcinoma with a favorable safety profile when an adequate dose and coverage were applied. Multimodality treatment with surgery should be considered for reirradiation or vertebral metastasis. A higher radiation dose may be required in patients who received previous systemic therapies.

In this edition of the Gastrointestinal Oncology Scan, our group has selected several interesting updates of large wellknown randomized trials, and a recent phase 2 trial, that shed further light on earlier results and highlight ongoing areas of debate. These offer a nice complement to some of our earlier Oncology Scans, bringing you the best literature around the journal landscape in gastrointestinal cancers (1-4). The first is the CROSS trial, a landmark study from the Netherlands, which established preoperative radiation given concurrently with carboplatin and paclitaxel, as opposed to surgery alone, as the standard of care for esophageal cancer (5). The follow-up publication provides patterns of failure data, which confirms the expected local control benefit of radiation therapy (6). The second trial is an update on the well-known German Rectal Trial, which cemented preoperative chemoradiation as standard therapy for locally advanced rectal cancer (7). The updated analysis provides important data on the correlation of pathologic response and disease outcome(8).Thequestionofadjuvantchemotherapy for patients with rectal cancer is highlighted in the third update of the EORTC 22921 trial (9). Many clinicians extrapolate from colon cancer data to support the use of adjuvant chemotherapy for high-risk patients. The long-term results of this trial question the soundness of that approach. Finally, the last report we discuss is a phase 2 trial from investigators at Memorial-Sloan Kettering using preoperative chemotherapy alone for locally advanced rectal cancer (10). The results suggest that for carefully selected patients, radiation may be omitted without a compromise in outcome. This approachisnowbeingtestedinarandomizedprospectivetrial.

The purpose of this study was to analyze the pretreatment setup errors and intrafraction motion using cone beam computed tomography (CBCT) for stereotactic body radiation therapy patients immobilized and localized with a stereotactic body frame for a variety of treatment sites.Localization errors were recorded for patients receiving SBRT for 141 lung, 29 liver, 48 prostate, and 45 spine tumors representing 1005 total localization sessions. All patients were treated in a stereotactic body frame with a large custom-molded vacuum pillow. Patients were first localized to the frame using tattoos placed during simulation. Subsequently, the frame was aligned to the room lasers according to the stereotactic coordinates determined from the treatment plan. Every patient received a pretreatment and an intrafraction CBCT. Abdominal compression was used for all liver patients and for approximately 40% of the lung patients to reduce tumor motion due to respiration.The mean ± standard deviation pretreatment setup errors from all localizations were -2.44 ± 3.85, 1.31 ± 5.84, and 0.11 ± 3.76 mm in the anteroposterior, superoinferior, and lateral directions, respectively. The mean pretreatment localization results among all treatment sites were not significantly different (F test, P.05). For all treatment sites, the mean ± standard deviation intrafraction shifts were 0.33 ± 1.34, 0.15 ± 1.45, and -0.02 ± 1.17 mm in the anteroposterior, superoinferior, and lateral directions, respectively. The mean unidimensional intrafraction shifts were statistically different for several of the comparisons (P.05) as assessed by the Tukey-Kramer test.Despite the varied tumor locations, the pretreatment mean localization errors for all sites were found to be consistent among the treatment sites and not significantly different, indicating that the body frame is a suitable immobilization and localization device for a variety of tumor sites. Our pretreatment localization errors and intrafraction shifts compare favorably with those reported in other studies using different types of immobilization devices.

Historically, both local as well as distant failure rates were unsatisfactory for locally advanced rectal tumors after surgery alone (1). Significant progress has been made on the local front with the introduction of mesorectal excision as well as neoadjuvant short-course radiation therapy or long-course chemoradiotherapy. In the German CAO/ARO/ AIO-94 trial, patients with clinical stage II or III rectal carcinoma treated with neoadjuvant radiation therapy and infusional 5-fluorouracil (5-FU), surgery, and 4 cycles of adjuvant bolus 5-FU had a 7.1% rate of localeregional failure at 10 years (2). The long-term control result from this trial provides an important benchmark for patients with clinical stage II and III rectal cancer going forward. The CAO/ARO/AIO-94 study also provides another important and concerning benchmark statistic: nearly 30% of the patients treated with neoadjuvant therapy developed distant metastatic disease by 10 years (2). Thus, locally advanced rectal adenocarcinoma would seem to be a prime candidate for true multimodality therapy, with a calling for effective systemic therapy above and beyond what is delivered as a radiosensitizer concurrently with radiation therapy during neoadjuvant therapy. The integration of localeradiation and surgeryetherapies and systemic therapy is founded on the principle of spatial cooperation and is the basis for many common cancer treatment algorithms (3). Adjuvant chemotherapy for resected rectal cancer would seem all the more natural given the data from

Purpose Cranial irradiation in pediatric patients is associated with serious long-term adverse effects. We sought to determine whether both three-dimensional conformal proton radiotherapy (3D-PRT) and intensity-modulated proton therapy (IMPT) compared with intensity-modulated radiotherapy (IMRT) decrease integral dose to brain areas known to harbor neuronal stem cells, major blood vessels, and other normal brain structures for pediatric patients with craniopharyngiomas. Methods and Materials IMRT, forward planned, passive scattering proton, and IMPT plans were generated and optimized for 10 pediatric patients. The dose was 50.4 Gy (or cobalt Gy equivalent) delivered in 28 fractions with the requirement for planning target volume (PTV) coverage of 95% or better. Integral dose data were calculated from differential dose–volume histograms. Results The PTV target coverage was adequate for all modalities. IMRT and IMPT yielded the most conformal plans in comparison to 3D-PRT. Compared with IMRT, 3D-PRT and IMPT plans had a relative reduction of integral dose to the hippocampus (3D-PRT, 20.4; IMPT, 51.3% ∗ ), dentate gyrus (27.3, 75.0% ∗ ), and subventricular zone (4.5, 57.8% ∗ ). Vascular organs at risk also had reduced integral dose with the use of proton therapy (anterior cerebral arteries, 33.3 ∗ , 100.0% ∗ ; middle cerebral arteries, 25.9% ∗ , 100% ∗ ; anterior communicating arteries, 30.8 ∗ , 41.7% ∗ ; and carotid arteries, 51.5 ∗ , 77.6 ∗ ). Relative reduction of integral dose to the infratentorial brain (190.7 ∗ , 109.7% ∗ ), supratentorial brain without PTV (9.6, 26.8% ∗ ), brainstem (45.6, 22.4% ∗ ), and whole brain without PTV (19.4 ∗ , 34.4% ∗ ) were recorded with the use of proton therapy. ( ∗ Differences were significant based on Friedman's test with Bonferroni-Dunn correction, α = 0.05) Conclusions The current study found that proton therapy was able to avoid excess integral radiation dose to a variety of normal structures at all dose levels while maintaining equal target coverage. Future studies will examine the clinical benefits of these dosimetric advantages.

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.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.Image data sets were collected from thirty-eight treatment fractions (14 patients). Mean differences between the two DTS methods and the CBCT method were1 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).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.

Purpose Conventional proton therapy with passively scattered beams is used to treat a number of tumor sites, including prostate cancer. Spot scanning proton therapy is a treatment delivery means that improves conformal coverage of the clinical target volume (CTV). Placement of individual spots within a target is dependent on traversed tissue density. Errors in patient alignment perturb dose distributions. Moreover, there is a need for a rational planning approach that can mitigate the dosimetric effect of random alignment errors. We propose a treatment planning approach and then analyze the consequences of various simulated alignment errors on prostate treatments. Methods and Materials Ten control patients with localized prostate cancer underwent treatment planning for spot scanning proton therapy. After delineation of the clinical target volume, a scanning target volume (STV) was created to guide dose coverage. Errors in patient alignment in two axes (rotational and yaw) as well as translational errors in the anteroposterior direction were then simulated, and dose to the CTV and normal tissues were reanalyzed. Results Coverage of the CTV remained high even in the setting of extreme rotational and yaw misalignments. Changes in the rectum and bladder V45 and V70 were similarly minimal, except in the case of translational errors, where, as a result of opposed lateral beam arrangements, much larger dosimetric perturbations were observed. Conclusions The concept of the STV as applied to spot scanning radiation therapy and as presented in this report leads to robust coverage of the CTV even in the setting of extreme patient misalignments.

This edition of the Oncology Scan is the first with a new could have received only radiosensitizing 5-fluorouracil or Gastrointestinal (GI) Editorial Team in place. We would first like to acknowledge Dr Brian Czito, who, after 2 years of fantastic service as one of the original associate editors, rotates out of the group. We also acknowledge the other outstanding members of our original group, Drs Jeffrey Meyer and Jennifer Wo, who are continuing on as associate editors. We welcome to our group Drs Stanley Liauw, Thomas Brunner, and Jason Chia-Hsien Cheng as new associate editors. For several years, they have been outstanding reviewers for this journal, and we are excited to have them join the editorial board. They each bring their own set of clinical and academic expertise in the field of GI cancers, and we look forward to working with them. Finally, we acknowledge Dr Christopher Willett, who was the first senior editor of the GI section. For 2 years, Dr Willett has provided invaluable leadership, mentorship, and support to the associate editors as he led our group in defining a vision and standard for the types of papers we sought to publish and organizing our selection process to ensure timely and constructive reviews. As a result, these past 2 years have seen a noticeable rise in the caliber of manuscripts received and ultimately selected for publication, and we hope to continue this success.

Purpose To compare the cost-effectiveness of intensity modulated radiation therapy (IMRT) and 3-dimensional conformal radiation therapy (3D-CRT) for anal cancer and determine disease, patient, and treatment parameters that influence the result. Methods and Materials A Markov decision model was designed with the various disease states for the base case of a 65-year-old patient with anal cancer treated with either IMRT or 3D-CRT and concurrent chemotherapy. Health states accounting for rates of local failure, colostomy failure, treatment breaks, patient prognosis, acute and late toxicities, and the utility of toxicities were informed by existing literature and analyzed with deterministic and probabilistic sensitivity analysis. Results In the base case, mean costs and quality-adjusted life expectancy in years (QALY) for IMRT and 3D-CRT were $32,291 (4.81) and $28,444 (4.78), respectively, resulting in an incremental cost-effectiveness ratio of $128,233/QALY for IMRT compared with 3D-CRT. Probabilistic sensitivity analysis found that IMRT was cost-effective in 22%, 47%, and 65% of iterations at willingness-to-pay thresholds of $50,000, $100,000, and $150,000 per QALY, respectively. Conclusions In our base model, IMRT was a cost-ineffective strategy despite the reduced acute treatment toxicities and their associated costs of management. The model outcome was sensitive to variations in local and colostomy failure rates, as well as patient-reported utilities relating to acute toxicities.

to normal tissues near the RT site but were reduced by 46 Gy until normal tissue constraints were allowed. The primary endpoint of this study was the tumor response according to the modified Response Evaluation Criteria in Solid Tumors criteria after RT following incomplete TACE in unresectable HCC. Secondary endpoints were patterns of failure, progression-free survival (PFS), time to tumor progression (TTP), overall survival (OS) rates at 2 years, and treatment-associated toxicity. Survival was calculated from the start of RT using the Kaplan-Meier method. Any factor that influenced prognosis in univariate analyses were subjected to multivariate analyses using the Cox proportional hazards regression model. Results: Between August 2008 and December 2010, 31 patients were enrolled. RTwas delivered with a median total dose 54 Gy (range, 46-59.4 Gy) in 1.8 to 2 Gy per fraction. Most patients (29 patients, 93.5%) received RT with a total dose 54 Gy. A best objective in-field response rate was achieved in 83.9% of patients with complete response (CR) in 22.6% of patients and partial response (PR) in 61.3% of patients within 12 weeks post-RT. A best overall response rate was achieved in 64.5% of patients with CR in 19.4% of patients and PR in 45.1% of patients. The 2-year IFPFS, PFS, TTP, and OS rates were 45.2%, 29.0%, 36.6%, and 61.3%, respectively. The Barcelona-Clinic Liver Cancer stage was identified as significant independent prognostic factor for PFS (P Z 0.023). Overall, 22 patients (59.1%) had treatment failures. Hepatic in-field failure occurred in 10 patients (32.3%), hepatic out-of-field failure occurred in 11 patients (35.5%), and extrahepatic failure (distant metastasis) occurred in 13 patients (41.9%). The lung was the most common site for distant metastases. Classic radiation-induced liver disease was not observed. There was no treatment-related death or hepatic failure. Conclusions: Three-dimensional-CRT following incomplete TACE achieves a promising objective response rate and is a safe and practical treatment option for patients with unresectable HCC. Acknowledgment: This work was supported by a grant (0620390) from the National RandD Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea. Author Disclosure: C. Choi: E. Research Grant; W. Koom: E. Research Grant; T. Kim: None. S. Yoon: None. J. Kim: None. H. Lee: None. T. Nam: None. J. Seong: E. Research Grant

(RT/CT) underwent serial MRI before (1st MRI) and during RT at 2–2.5 weeks (2nd MRI, at 20–25 Gy), at 4–5 weeks of RT (3rd MRI, at 45–50 Gy), and 1–2 months post-RT. Mean follow up was 6.2 (0.2–9.4) years. Tumor volume was measured by MRI 3D volumetry, and plotted as time/tumor volume regression curves. The volume regression parameters were correlated with local tumor control and disease-free survival.