Search

Patients undergoing radiation therapy may terminate treatment for any number of reasons. The incidence of treatment termination (TT) during radiation therapy has not been studied. Herein, we present a cohort of TT at a large multicenter radiation oncology department over 10 years. TTs between January 2013 and January 2023 were prospectively analyzed as part of an ongoing departmental quality and safety program. TT was defined as any premature discontinuation of therapy after initiating radiation planning. The rate of TT was calculated as a percentage of all patients starting radiation planning. All cases were presented at monthly morbidity and mortality conferences with a root cause reviewed. A total of 1448 TTs were identified out of 31,199 planned courses of care (4.6%). Six hundred eighty-six (47.4%) involved patients treated with curative intent, whereas 753 (52.0%) were treated with palliative intent, and 9 (0.6%) were treated for benign disease. The rate of TT decreased from 8.49% in 2013 to 3.02% in 2022, with rates decreasing yearly. The most common disease sites for TT were central nervous system (21.7%), head and neck (19.3%), thorax (17.5%), and bone (14.2%). The most common causes of TT were hospice and/or patient expiration (35.9%), patient choice unrelated to toxicity (35.2%), and clinician choice unrelated to toxicity (11.5%). This 10-year prospective review of TTs identified a year-over-year decrease in TTs as a percentage of planned patients. This decrease may be associated with the addition of root cause reviews for TTs and discussions monthly at morbidity and mortality rounds, coupled with departmental upstream quality initiatives implemented over time. Understanding the reasons behind TTs may help decrease preventable TTs. Although some TTs may be unavoidable, open discourse and quality improvement changes effectively reduce TT incidents over time. [ABSTRACT FROM AUTHOR]

In a prospective multicenter study, gemcitabine monotherapy followed by stereotactic body radiation therapy (SBRT) was well tolerated with outcomes comparable to chemoradiation for locally advanced pancreatic cancer (LAPC). Recent trials have reported improved survival with multiagent chemotherapy (MA-CTX) alone. This prospective trial explored whether SBRT could be safely delivered after MA-CTX. Herein, we report the long-term outcomes of adding SBRT after MA-CTX in LAPC patients and evaluate whether genetic profiles of specimens obtained before SBRT influence outcomes. This prospective nonrandomized controlled phase 2 trial enrolled 44 LAPC and 4 locally recurrent patients after multidisciplinary evaluation between 2012 and 2015 at a high-volume pancreatic cancer center. For induction CTX, most received modified FOLFIRINOX (mFFX), or gemcitabine and nab-paclitaxel (GnP) followed by 5-fraction SBRT for all. During fiducial placement, biopsies were obtained with DNA extracted for targeted sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets platform. Median induction CTX duration was ≥4 months, and 31 patients received mFFX (65%). Among 44 LAPC patients, 17 (39%) were surgically explored, and 12 of 16 (75%) achieved a R0 resection. Median overall survival (mOS) was 20.2 and 14.6 months from diagnosis and SBRT, respectively. One- and 2-year OS from SBRT was 58% and 28%. The mOS after resection was 28.6 and 22.4 months from diagnosis and SBRT, respectively. Median local progression-free survival was 23.9 and 15.8 months from diagnosis and SBRT, respectively. The mOS for pre-SBRT CA 19-9 ≤180 U/mL versus >180 was 23.1 and 11.3 months, respectively (hazard ratio, 0.53; P =.04). Only 1 patient (2.1%) had late grade ≥2 gastrointestinal toxic effects attributable to SBRT. Despite significant pretreatment with chemotherapy, 88% of tumor specimens were effectively sequenced; survival outcomes were not significantly associated with specific mutational patterns. Quality of life was prospectively collected pre- and post-SBRT with the EORTC QLQ-C30 and PAN26 questionnaires showing no significant change. SBRT was safely administered with MA-CTX with minimal toxicity. A high proportion of LAPC patients underwent R0 resection with favorable survival outcomes. [ABSTRACT FROM AUTHOR]

In patients with borderline resectable or locally advanced pancreatic adenocarcinoma (BRPC/LAPC), local failure rates after resection remain significant, even in the setting of neoadjuvant chemotherapy and radiation. Suboptimal local control may relate to variable radiation target delineation, as no consensus exists around clinical tumor volume (CTV) design in this context. In the surgical literature, recent attention has been given to the "triangle" volume (TV) as a source of subclinical, residual disease. To understand whether the TV can inform optimal CTV design, we mapped locoregional failures after resection in a large cohort of patients with BRPC/LAPC and compared locations of failure to the TV. Patients with BRPC/LAPC of the head or neck diagnosed between 2016 AND 2019 who developed locoregional failure after surgery, neoadjuvant chemotherapy, and radiation were identified. Descriptive statistics were generated to report the frequency of locoregional failures located within the TV and the frequency of new vascular involvement at time of failure, compared with vascular involvement at diagnosis. Additionally, dosimetric coverage of the TV with the preoperative radiation plan that had been used was assessed. In 31 patients who experienced locoregional failure, the centroid of failure was located within the TV in 28 cases (90%). Extent of vascular involvement at time of locoregional failure included vasculature that had not been involved at diagnosis in 13 cases (42%). The preoperative radiation plan that had been used provided a median V33 Gy and V25 Gy of the TV of only 53% (interquartile range, 34%-72%) and 70% (IQR, 48%-85%), respectively. The TV encompassed the vast majority of locoregional failures, but dosimetric coverage of the TV was poor when only targeting gross disease and the full circumference of involved vasculature. As such, the TV may better serve as a basis for CTV design in patients with BRPC/LAPC undergoing neoadjuvant radiation. [ABSTRACT FROM AUTHOR]

The timing and the dose of Advanced Care Planning in patients with pancreatic ductal adenocarcinoma undergoing curative-intent resection are generally dictated by the surgeon performing the operation. A qualitative investigation using 1:1 interviews with 40 open-ended questions was conducted with a convenience sample of 10 high-volume pancreatic surgeons from across the country. The grounded theory approach was used for data analysis. A total of 10 interviews were conducted with expert pancreatic surgeons—6 males and 4 females. During preoperative counseling, all surgeons attempt to motivate patients by emphasizing hope, optimism, and the fact that surgery offers the only opportunity for cure. All surgeons discuss the possibility of recurrence as well as postoperative complications; however, a majority perceived that patients do not fully appreciate the likelihood of recurrence or postoperative complications. All surgeons acknowledged the importance of end-of-life conversations when death is imminent. Seventy percent of surgeons had mixed opinions regarding benefits of preoperative Advanced Care Planning in the preoperative setting, while 20% felt it was definitely beneficial, particularly that delivery of care aligned with patient goals. All surgeons emphasized that Advanced Care Planning should be led by a physician who both knows the patient well and understands the nuances of pancreatic ductal adenocarcinoma management. Most common barriers to in-depth Advanced Care Planning discussion reported by surgeons include taking away hope, lack of time, and concern for sending "mixed messages." We identified that surgeons experience a fundamental tension between promoting realistic long-term goals and expectations versus focusing on hope and enabling an overly optimistic perception of prognosis. [ABSTRACT FROM AUTHOR]

We assessed the feasibility and safety of placing a radiopaque hydrogel in the pancreaticoduodenal groove via endoscopic ultrasound guidance in patients with borderline resectable/locally advanced pancreatic cancer (BR/LAPC). Hydrogel injections were done at time of fiducial placement to form blebs in the pancreaticoduodenal groove. Patients subsequently underwent simulation computed tomography (sim-CT) followed by hypofractionated stereotactic body radiotherapy (SBRT; 33 Gy in 5 fractions). Four to 8 weeks after SBRT, patients underwent CT re-evaluation for surgical candidacy and assessment of hydrogel location and size. Hydrogel placement was considered successful if identified in the pancreaticoduodenal groove on sim-CT scan. Stability was evaluated using equivalence testing analyses, with a null hypothesis of the presence of a ≥20% mean percentage change in volume and ≥2 mm change in the median and mean interbleb surface distance with a P value <.05 required to reject the null hypothesis and conclude equivalence. For patients undergoing pancreaticoduodenectomy, hydrogel sites were histologically examined for location and local inflammatory reactions. Hydrogel placement was successful in 6 of the 6 evaluable patients. The average changes in median and mean interbleb distances were −0.43 mm and −0.35 mm, respectively, with P <.05. The average change in volume from sim-CT to post-SBRT CT was −1.0%, with P <.05. One patient experienced grade 3 nausea after fiducial/hydrogel placement, with no other adverse events to date. These data demonstrate feasibility and safety of injecting a hydrogel marker in the pancreaticoduodenal groove in patients with BR/LAPC and set the stage for a follow-up clinical trial to place hydrogel as a spacer between the pancreatic tumor and dose-limiting, radiosensitive duodenum. [ABSTRACT FROM AUTHOR]

To provide a detailed description of practical approaches to dose escalation in pancreatic cancer. The current paper represents an international collaborative effort of radiation oncologists from the MR-linac consortium with expertise in pancreatic dose escalation. A 15-fraction hypofractionated intensity modulated radiation therapy (67.5 Gy in 15 fractions) and 5-fraction stereotactic body radiation therapy case (50 Gy in 5 fractions) are presented with information regarding patient selection, target volumes, organs at risk, dose constraints, and specific considerations regarding quality assurance. Additionally, we address barriers to dose escalation and briefly discuss future directions in dose escalation for pancreatic cancer, including particle therapy and magnetic resonance guided radiation therapy. This article on dose escalation for pancreatic cancer may help to guide academic and community based physicians and to serve as a reference for future therapeutic trials. [ABSTRACT FROM AUTHOR]

The purpose of this study was to quantitatively evaluate the visibility and artifacts of commercially available fiducial markers to optimize their selection for image guided stereotactic body radiation therapy. From 6 different vendors, we selected 11 fiducials commonly used in image guided radiation therapy. The fiducials varied in material composition (e.g., gold, platinum, carbon), shape (e.g., cylindrical, notched/linear, coiled, ball-like, step), and size measured in terms of diameter (0.28-1.0 mm) and length (3.0-20.0 mm). Each fiducial was centered in 4-mm bolus within a 13-cm-thick water-equivalent phantom. Fiducials were imaged with the use of a simulation computed tomography (CT) scanner, a CT-on-rails system, and an onboard cone beam CT system. Acquisition parameters were set according to clinical protocols. Visibility was assessed in terms of contrast (Δ Hounsfield unit [HU]) and the Michelson visibility metric. Artifacts were quantified in terms of relative standard deviation and relative streak artifacts level (rSAL). Twelve radiation oncologists ranked each fiducial in terms of clinical usefulness. Contrast and artifacts increased with fiducial size. For CT imaging, maximum contrast (2722 HU) and artifacts (rSAL = 2.69) occurred for the largest-diameter (0.75 mm) platinum fiducial. Minimum contrast (551 HU) and reduced artifacts (rSAL = 0.65) were observed for the smallest-diameter (0.28 mm) gold fiducial. Carbon produced the least severe artifacts (rSAL = 0.29). The survey indicated that physicians preferred gold fiducials with a 0.35- to 0.43-mm diameter, 5- to 10-mm length, and coiled or cylindrical shape that balanced contrast and artifacts. We evaluated 11 different fiducials in terms of visibility and artifacts. The results of this study may assist radiation oncologists who seek to maximize contrast, minimize artifacts, or balance contrast versus artifacts by fiducial selection. [ABSTRACT FROM AUTHOR]

Local recurrences can sometimes occur after prior radiotherapy for abdominal and pelvic cancers. The management of these patients can be quite complex. We present a case of recurrent pancreatic cancer after prior chemoradiation and discuss various management options, with a focus on different approaches to reirradiation. [ABSTRACT FROM AUTHOR]

Active Breathing Coordinator (Elekta AB, Crawley, UK) is a motion management strategy for radiation treatment. During setup, aligning the patient to the bony spine alone does not necessarily lead to an accurate alignment to soft tissue targets, and further adjustment is necessary. Determining a safe range of values for such adjustments is an important quality assurance measure and was the purpose of this study, with focus on stereotactic body radiation therapy in patients with pancreatic cancer. The retrospective study included 19 previously treated patients. For each fraction, a free-breathing cone beam computed tomography scan was registered to a reference breath-hold computed tomography for alignment to the spine. Two perpendicular breath-hold kV projection images were then acquired and compared with corresponding reference digitally reconstructed radiographs for additional alignment with a surrogate fiducial marker. By comparing the breath-hold kV projection images from subsequent treatment fractions with those from the first fraction, we derived the 3-dimensional variability of the fiducial position with respect to the reference image. We observed intrafraction setup error to be within 2.0 mm. For interfraction, we observed average reproducibility of 1.7 ± 0.8 mm, 2.0 ± 1.4 mm, and 3.2 ± 2.5 mm in the left–right (LR), anterior–posterior (AP), and superior–inferior (SI) directions, respectively. The average excursion values from free breathing spine to breath-hold fiducial alignment were 1.5 ± 1.4 mm, 2.0 ± 1.9 mm, and 3.0 ± 2.0 mm in the LR, AP and SI directions, respectively. The observed ranges of average excursions among all patients were 0.2 to 5.1 mm, 0.1 to 5. 9 mm, and 0.6 to 7.8 mm in the LR, AP, and SI directions, respectively. This study demonstrates that intrafraction targeting errors can be within 2 mm, and interfraction shifts from free-breathing spine to Active Breathing Coordinator breath-hold target can be as high as 8 mm. Values that deviate significantly would need further investigation to rule out factors such as local progression, bowel gas, or fiducial shift before treatment. [ABSTRACT FROM AUTHOR]

Background The impact of neoadjuvant stereotactic body radiation therapy on postoperative complications for patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma remains unclear. Limited studies have compared neoadjuvant stereotactic body radiation therapy versus conventional chemoradiation therapy. A retrospective study was performed to determine if perioperative complications were different among patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma receiving neoadjuvant stereotactic body radiation therapy or chemoradiation therapy. Methods Patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma who underwent neoadjuvant chemotherapy with stereotactic body radiation therapy or chemoradiation therapy followed by pancreatectomy at the Johns Hopkins Hospital between 2008 and 2015 were included. Predictive factors for severe complications (Clavien grade ≥ III) were assessed by univariate and multivariate analyses. Results A total of 168 patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma underwent neoadjuvant chemotherapy and RT followed by pancreatectomy. Sixty-one (36%) patients underwent stereotactic body radiation therapy and 107 (64%) patients received chemoradiation therapy. Compared with the chemoradiation therapy cohort, the neoadjuvant stereotactic body radiation therapy cohort was more likely to have locally advanced pancreatic ductal adenocarcinoma (62% vs 43% P  = .017) and a require vascular resection (54% vs 37%, P  = .027). Multiagent chemotherapy was used more commonly in the stereotactic body radiation therapy cohort (97% vs 75%, P  < .001). Postoperative complications (Clavien grade ≥ III 23% vs 28%, P  = .471) were similar between stereotactic body radiation therapy and chemoradiation therapy cohort. No significant difference in postoperative bleeding or infection was noted in either group. Conclusion Compared with chemoradiation therapy, neoadjuvant stereotactic body radiation therapy appears to offer equivalent rates of perioperative complications in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma despite a greater percentage of locally advanced disease and more complex operative treatment. [ABSTRACT FROM AUTHOR]

Although most patients with pancreatic cancer die of metastatic disease, an autopsy study showed that up to one-third of patients die of predominantly local disease. This patient population stands to benefit the most from radiation, surgery, or both. Unfortunately, however, single-agent chemotherapy has had minimal benefit in pancreatic cancer, and most patients progress distantly before receiving radiation therapy (RT). With the addition of multiagent chemotherapy, patients are living longer, and RT has emerged as an important modality in preventing local progression. Standard chemoradiation delivered over 5-6 weeks has been shown to improve local control, but this approach delays full-dose systemic therapy and increases toxicity when compared to chemotherapy alone. Stereotactic body RT (SBRT) delivered in 3-5 fractions can be used to accurately target the pancreatic tumor with small margins and limited acute treatment-related toxicity. Given the favorable toxicity profile, SBRT can easily be integrated with other therapies in all stages of pancreatic cancer. However, future studies are necessary to determine optimal dose or fractionation regimens and sequencing with targeted therapies and immunotherapy. The purpose of this review is to discuss our current understanding of SBRT in the multidisciplinary management of patients with pancreatic cancer and future implications. [ABSTRACT FROM AUTHOR]

Purpose We previously reported clinical outcomes and physician-reported toxicity of gemcitabine and hypofractionated stereotactic body radiation therapy (SBRT) in locally advanced pancreatic cancer (LAPC). Here we prospectively investigate the impact of gemcitabine and SBRT on patient-reported quality of life (QoL). Methods and materials Forty-nine LAPC patients received 33 Gy SBRT (6.6 Gy daily fractions) upfront or after ≤ 3 doses of gemcitabine (1000 mg/m 2 ) followed by gemcitabine until progression. European Organization for Research and Treatment of Cancer QoL core cancer (QLQ-C30) and pancreatic cancer-specific (European Organization for Research and Treatment of Cancer QLQ-PAN26) questionnaires were administered to patients pre-SBRT and at 4 to 6 weeks (first follow-up [1FUP]) and 4 months (2FUP) post-SBRT. Changes in QoL scores were deemed clinically relevant if median changes were at least 5 points in magnitude. Results Forty-three (88%) patients completed pre-SBRT questionnaires. Of these, 88% and 51% completed questionnaires at 1FUP and 2FUP, respectively. There was no change in global QoL from pre-SBRT to 1FUP ( P = .17) or 2FUP ( P > .99). Statistical and clinical improvements in pancreatic pain ( P = .001) and body image ( P = .007) were observed from pre-SBRT to 1FUP. Patients with 1FUP and 2FUP questionnaires reported statistically and clinically improved body image ( P = .016) by 4 months. Although pancreatic pain initially demonstrated statistical and clinical improvement ( P = .020), scores returned to enrollment levels by 2FUP ( P = .486). A statistical and clinical decline in role functioning ( P = .002) was observed in patients at 2FUP. Conclusions Global QoL scores are not reduced with gemcitabine and SBRT. In this exploratory analysis, patients experience clinically relevant short-term improvements in pancreatic cancer-specific symptoms. Previously demonstrated acceptable clinical outcomes combined with these favorable QoL data indicate that SBRT can be easily integrated with other systemic therapies and may be a potential standard of care option in patients with LAPC. [ABSTRACT FROM AUTHOR]

Purpose To summarize results of a Clinical Practice Statement on radiation therapy for stage II-III rectal cancer, which addressed appropriate customization of (neo)adjuvant radiation therapy and use of non-surgical therapy for patients who are inoperable or refuse abdominoperineal resection. Methods and materials The RAND/University of California, Los Angeles, Appropriateness Method was applied to combine current evidence with multidisciplinary expert opinion. A systematic literature review was conducted and used by the expert panel to rate appropriateness of radiation therapy options for different clinical scenarios. Treatments were categorized by median rating as Appropriate, May Be Appropriate, or Rarely Appropriate. Results In the neoadjuvant setting, chemoradiation was rated Appropriate and the ratings indicated short-course radiation therapy, chemotherapy alone, and no neoadjuvant therapy are potential options in selected patients. However, neoadjuvant endorectal brachytherapy was rated Rarely Appropriate. For adjuvant therapy, chemoradiation (plus ≥ 4 months of chemotherapy) was rated Appropriate and chemotherapy alone May Be Appropriate for most scenarios. For medically inoperable patients, definitive external beam radiation therapy and chemotherapy alone were rated May Be Appropriate, whereas endorectal brachytherapy and chemoradiation plus endorectal brachytherapy were possible approaches for some scenarios. The last option, definitive chemoradiation, was rated Appropriate to May Be Appropriate based on performance status. Finally, for patients with low-lying tumors refusing abdominoperineal resection, definitive chemoradiation alone, chemoradiation plus endorectal brachytherapy, and chemoradiation plus external beam radiation therapy were all rated Appropriate. Conclusions This Clinical Practice Statement demonstrated the central role of radiation therapy in stage II-III rectal cancer management and evaluated ways to better individualize its use in the neoadjuvant, adjuvant, and definitive settings. Ongoing trials may clarify areas of continuing uncertainty and allow further customization. [ABSTRACT FROM AUTHOR]

Purpose: Radiation-induced lymphopenia (RIL) is associated with inferior survival in patients with glioblastoma, lung cancer, and pancreatic cancer. We asked whether stereotactic body radiation therapy (SBRT) decreases severity of RIL compared to conventional chemoradiation therapy (CRT) in locally advanced pancreatic cancer (LAPC).Methods and Materials: Serial total lymphocyte counts (TLCs) from patients enrolled in a prospective trial of SBRT for LAPC were compared to TLCs from an existing database of LAPC patients undergoing definitive CRT. SBRT patients received 33 Gy (6.6 Gy × 5 fractions). CRT patients received a median dose of 50.4 Gy (1.8 Gy × 28 fractions) with concurrent 5-fluorouracil (77%) or gemcitabine (23%) therapy. Univariate and multivariate analyses (MVA) were used to identify associations between clinical factors and post-treatment TLC and between TLC and survival.Results: Thirty-two patients received SBRT and 101 received CRT. Median planning target volume (PTV) was smaller in SBRT (88.7 cm(3)) than in CRT (344.6 cm(3); P<.001); median tumor diameter was larger for SBRT (4.6 cm) than for CRT (3.6 cm; P=.01). SBRT and CRT groups had similar median baseline TLCs. One month after starting radiation, 71.7% of CRT patients had severe lymphopenia (ie, TLC <500 cells/mm(3) vs 13.8% of SBRT patients; P<.001). At 2 months, 46.0% of CRT patients remained severely lymphopenic compared with 13.6% of SBRT patients (P=.007). MVA demonstrated that treatment technique and baseline TLCs were significantly associated with post-treatment TLC at 1 but not 2 months after treatment. Higher post-treatment TLC was associated with improved survival regardless of treatment technique (hazard ratio [HR] for death: 2.059; 95% confidence interval: 1.310-3.237; P=.002).Conclusions: SBRT is associated with significantly less severe RIL than CRT at 1 month in LAPC, suggesting that radiation technique affects RIL and supporting previous modeling studies. Given the association of severe RIL with survival in LAPC, further study of the effect of radiation technique on immune status is warranted. [ABSTRACT FROM AUTHOR]

Purpose To determine the health-related quality of life (QOL) during and after neoadjuvant chemoradiation therapy and surgery for patients with pancreatic adenocarcinoma. Methods and Materials Participants of a prospective, phase 2 multi-institutional trial treated with neoadjuvant chemoradiation followed by surgery completed QOL questionnaires (European Organization for Research and Treatment in Cancer Quality of Life Questionnaire version 3.0 [EORTC-QLQ C30], EORTC-Pancreatic Cancer module [EORTC-PAN 26], and Functional Assessment of Cancer Therapy Hepatobiliary and Pancreatic subscale [FACT-Hep]) at baseline, after 2 cycles of neoadjuvant therapy, after surgery, at 6 months from initiation of therapy, and at 6-month intervals for 2 years. Mean scores were compared with baseline. A change >10% was considered a minimal clinically important difference. Results Of 71 participants in the trial, 55 were eligible for QOL analysis. Compliance ranged from 32% to 74%. The EORTC-QLQ C30 global QOL did not significantly decline after neoadjuvant therapy, whereas the Functional Assessment of Cancer Therapy global health measure showed a statistically, but not clinically significant decline (−8, P =.02). This was in parallel with deterioration in physical functioning (−14.1, P =.001), increase in diarrhea (+16.7, P =.044), and an improvement in pancreatic pain (−13, P =.01) as per EORTC-PAN 26. Because of poor patient compliance in the nonsurgical group, long-term analysis was performed only from surgically resected participants (n=36). Among those, global QOL returned to baseline levels after 6 months, remaining near baseline through the 24-month visit. Conclusions The study regimen consisting of 2 cycles of neoadjuvant therapy was completed without a clinically significant QOL deterioration. A transient increase in gastrointestinal symptoms and a decrease in physical functioning were seen after neoadjuvant chemoradiation. In those patients who underwent surgical resection, most domains returned back to baseline levels by 6 months. [ABSTRACT FROM AUTHOR]

Background Race-based disparities in operative morbidity and mortality have been demonstrated for various procedures, including pancreatoduodenectomy (PD). Race-based differences in hospital length-of-stay (LOS), especially related to provider volume at the surgeon and hospital level, remain poorly defined. Methods Using the 2003-2009 Nationwide Inpatient Sample, we determined year-specific PD volumes for surgeons and hospitals and grouped them into terciles. Patient race (white, black, or Hispanic), age, sex, and comorbidities were examined. Median length of stay was calculated, and multivariable logistic regression was used to examine factors associated with increased LOS. Results Among 4,319 eligible individuals, 3,502 (81.1%) were white, 423 (9.8%) were black, and 394 (9.1%) were Hispanic. Overall median LOS was 12 days (range, 0-234). Median annual surgeon volume was 8 (interquartile range [IQR], 2-19; range, 1-54). Annual hospital volume ranged from 1 to 129 (median, 19; IQR, 7-55). White patients were more likely to have been treated at medium- to high-volume hospitals (odds ratio [OR] 1.53, P < .001) and by medium- to high-volume surgeons (OR 1.62, P < .001) than black or Hispanic patients. After PD, white, black, and Hispanic patients demonstrated similar in-hospital mortality (5.1%, 5.7% and 7.2% respectively P = .250). After adjustment, black (OR 1.36, P = .010) and Hispanic (OR 1.68, P < .001) patients were more likely to have a greater LOS after PD. Conclusion Black and Hispanic PD patients were less likely than white patients to be treated at higher-volume hospitals and by higher-volume surgeons. Proportional mortality and LOS after PD were greater among black and Hispanic patients. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To standardize upper abdominal normal organ contouring guidelines for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials: Twelve expert radiation oncologists contoured the liver, esophagus, gastroesophageal junction (GEJ), stomach, duodenum, and common bile duct (CBD), and reviewed and edited 33 additional normal organ and blood vessel contours on an anonymized patient computed tomography (CT) dataset. Contours were overlaid and compared for agreement using MATLAB (MathWorks, Natick, MA). S95 contours, defined as the binomial distribution to generate 95% group consensus contours, and normal organ contouring definitions were generated and reviewed by the panel. Results: There was excellent consistency and agreement of the liver, duodenal, and stomach contours, with substantial consistency for the esophagus contour, and moderate consistency for the GEJ and CBD contours using a Kappa statistic. Consensus definitions, detailed normal organ contouring recommendations and high-resolution images were developed. Conclusions: Consensus contouring guidelines and a CT image atlas should improve contouring uniformity in radiation oncology clinical planning and RTOG trials. [Copyright &y& Elsevier]

Background: We sought to define the utilization and effect of adjuvant external-beam radiotherapy (XRT) on patients having undergone curative-intent resection for gallbladder cancer (GBC). Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 5,011 patients with GBC who underwent resection between 1988 and 2009. The impact of XRT on survival was analyzed by the use of propensity-score matching by comparing clinicopathologic factors between patients who received resection only versus resection plus XRT. Results: Median age was 72 years, and most patients were female (73.4%); 66.2% patients had intermediate to poorly differentiated tumors, and 19.1% had lymph node metastasis. The majority (75.0%) had “localized” disease by Surveillance, Epidemiology, and End Results classification. A total of 899 patients (17.9%) received XRT whereas 4,112 patients did not. Factors associated with receipt of XRT were younger age (odds ratio [OR] 5.33), tumor extension beyond the serosa (OR 1.55), intermediate- to poorly differentiated tumors (OR 1.56), and lymph node metastasis (OR 2.59) (all P < .05). Median and 1-year survival were 15 months and 59.0%, respectively. On propensity-matched multivariate model, despite having more advanced tumors, XRT was independently associated with better long-term survival at 1 year (hazard ratio 0.45; P < .001), but not 5 years (hazard ratio 1.06; P = .50). Conclusion: A total of 18% of patients with GBC received XRT after curative intent surgery. The use of adjuvant XRT was associated with a short-term survival benefit, but the benefit dissipated over time. [Copyright &y& Elsevier]

Background: Assessment of patient performance status is often subjective. Sarcopenia—measurement of muscle wasting—may be a more objective means to assess performance status and therefore mortality risk following intra-arterial therapy (IAT). Methods: Total psoas area (TPA) was measured on cross-sectional imaging in 216 patients undergoing IAT of hepatic malignancies between 2002 and 2012. Sarcopenia was defined as TPA in the lowest sex-specific quartile. Impact of sarcopenia was assessed relative to other clinicopathological factors. Results: Indications for IAT included hepatocellular carcinoma (51 %), intrahepatic cholangiocarcinoma (13 %), colorectal liver metastasis (7 %), or other metastatic disease (30 %). Median TPA among men (568 mm 2/m 2) was greater than women (413 mm 2/m 2). IAT involved conventional chemoembolization (54 %), drug-eluting beads (40 %), or yttrium-90 (6 %). Median tumor size was 5.8 cm; most patients had multiple lesions (74 %). Ninety-day mortality was 9.3 %; 3-year survival was 39 %. Factors associated with risk of death were tumor size (HR = 1.84) and Child's score (HR = 2.15) (all P < 0.05). On multivariate analysis, sarcopenia remained independently associated with increased risk of death (lowest vs. highest TPA quartile, HR = 1.84; P = 0.04). Sarcopenic patients had a 3-year survival of 28 vs. 44 % for non-sarcopenic patients. Conclusions: Sarcopenia was an independent predictor of mortality following IAT with sarcopenic patients having a twofold increased risk of death. Sarcopenia is an objective measure of frailty that can help clinical decision-making regarding IAT for hepatic malignancies. [ABSTRACT FROM AUTHOR]

Introduction: Pancreatoblastoma is an extremely rare pancreatic neoplasm in adults. The aim of this study is to report our experience with adult pancreatoblastoma as well as review the cases reported in the literature in order to provide guidelines for the management of patients with this rare neoplasm. Methods: We have encountered three cases of pancreatoblastoma in adults at our institution in addition to the 30 cases reported to date in literature. Results: The median age of pancreatoblastoma in adults is 37 years (range, 18–78 years); men and women are similarly affected (male/female = 16/17). The behavior of pancreatoblastoma is clearly that of a malignant neoplasm, with local invasion, recurrence, and metastasis. Among the adult reported cases, at diagnosis or operation, metastasis and/or local invasion was found in 14 of 31 adult patients (46 %) (2 patients had no data) The survival was significantly higher in patients with resected tumor (resection only and resection + adjuvant chemo/radiotherapy) when compared to unresected patients (palliative chemo/radiotherapy and no treatment), ( p = 0.008, HR = 0.20). Conclusion: When disease is localized, the treatment of choice is a complete surgical resection. The role of adjuvant chemotherapy or radiotherapy is still unclear based on the very small number of patients treated. [ABSTRACT FROM AUTHOR]

Background: Little is known about current surveillance patterns after treatment of colorectal liver metastasis (CRLM) or whether the intensity of surveillance correlates with outcome. We sought to define current population-based patterns of surveillance and investigate whether intensity of surveillance impacted outcome. Methods: We queried the Surveillance, Epidemiology, and End Results–linked Medicare database for patients with CRLM diagnosed between 1991 and 2005 who underwent liver resection and/or tumor ablation. Frequency of post-treatment abdominal computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) was recorded for ≤5 years after treatment. The association between frequency of imaging with secondary interventions and long-term survival were analyzed. Results: We identified 1,739 patients with CRLM treated with surgery; median age was 73 years, and the majority were male (52.6%). CRLM treatment consisted of liver resection (61%), ablation (32%), or both simultaneously (6%). CT (97%) was utilized more often for post-treatment surveillance compared with MRI (7%) and PET (18%). A temporal trend was noted with more frequent surveillance imaging obtained in post-treatment year 1 (2.4 scans/year) versus year 5 (0.6 scans/year; P = .01); 66% of living patients had no imaging after 2 years. Frequency of surveillance imaging correlated with procedure type (total number of scans/5 years: resection, 5.0; ablation, 4.6; resection and ablation, 6.2; P = .01). Other factors associated with a greater frequency of surveillance included younger age at diagnosis, geographic location in the South, and CRLM directed surgery in 2000 through 2005 (all P < .05). Overall survival did not differ by intensity of surveillance imaging (3–4 scans/yr, 43 months vs 2 scans/yr, 57 months vs 1 scan/yr, 54 months; P = .08). Conclusion: Marked heterogeneity exists in how often surveillance imaging is obtained after treatment of CRLM. Intensity of imaging does not affect time to second procedure or median survival duration. Surveillance guidelines for CRLM need to be refocused to provide the best value for healthcare resources. [Copyright &y& Elsevier]

Background: Studies reporting perioperative outcomes after pancreaticoduodenectomy (PD) have focused on morbidity and mortality. Understanding factors that impact hospital duration of stay may have cost-saving implications. We sought to examine variation in duration of stay after PD occurring at the patient, surgeon, and hospital levels. Methods: Year-specific PD volumes for both surgeons and hospitals were determined from the 2003–2009 Nationwide Inpatient Sample and grouped into terciles. Patient age, gender, and comorbidities were examined. Median duration of stay was calculated and modified Poisson regression examined factors associated with duration of stay. Results: Among 5,190 individuals undergoing PD, median age was 65 years and 49.3% were female. Median duration of stay was 13 days (range, 0–234). Older patients and those with comorbid illness were more likely to have duration of stay of ≥14 days (P < .001). Median annual surgeon volume was 8 (interquartile range [IQR], 2–19; range, 1–54). Annual hospital volume ranged from 1 to 129 (median, 18; IQR, 6–52). Both low surgeon and hospital PD volume were associated with longer durations of stay (P < .001). In multivariable modeling, age remained associated with duration of stay (relative risk [RR], 1.007 per year; P < .001); however, comorbidity did not. Patients operated on by high-volume surgeons (RR, 0.67) or at high-volume hospitals (RR, 0.75) had a reduced risk of a prolonged duration of stay of ≥14 days (both P < .001). Conclusion: PD patients treated by higher volume surgeons and at higher volume hospitals had a shorter duration of stay. Although some patient-level factors impact duration of stay after PD, nonclinical factors such as surgeon and hospital volume were also important contributors to duration of stay. [Copyright &y& Elsevier]

Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m2 twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m2 on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer. [Copyright &y& Elsevier]

Background: EUS-guided fiducial placement facilitates image-guided radiation therapy (IGRT). Objective: To compare 2 types of commercially available fiducials for technical success, complications, visibility, and migration. Design: Retrospective, single-center, comparative study. Setting: Tertiary-care medical center. Interventions: Traditional fiducials (TFs) (5-mm length, 0.8-mm diameter) and Visicoil fiducials (VFs) (10-mm length, 0.35-mm diameter) were compared. Fiducials were placed using linear 19-gauge (for TFs) or 22-gauge (for VFs) needles. A subjective visualization scoring system (0-2; 0 = not visible, 1 = barely visible, 2 = clearly visible) was used to assess visibility on CT. Fiducial migration was calculated as a change in interfiducial distance. Main Outcome Measurements: Technical success, complications, visibility, and migration of 2 types of fiducials. Results: Thirty-nine patients with locally advanced pancreatic cancer underwent EUS-guided placement of 103 fiducials (77 TFs, 26 VFs). The mean number of fiducials placed per patient was 2.66 (standard deviation 0.67) for the 19-gauge needle and 2.60 (standard deviation 0.70) for the 22-gauge needle (P = .83). No intra- or postprocedural complications were encountered. The median visibility score for TFs was significantly better than that for VFs, both when scores of 0 were and were not included (2.00, interquartile range [IQR] 2.00-2.00 vs 1.75, IQR 1.50-2.00, P = .009 and 2.00, IQR 2.00-2.00 vs 2.00, IQR 1.50-2.00, P < .0001, respectively). The mean migration was not significantly different between the 2 types of fiducials (0.8 mm [IQR 0.4-1.6 mm] for TFs vs 1.3 mm [IQR 0.6-1.5 mm] for VFs; P = .72). Limitations: Retrospective, nonrandomized design. Conclusions: Visibility was significantly better for TFs compared with VFs. The degree of fiducial migration was not significantly different for TFs and VFs. There was no significant difference in the mean number of fiducials placed, indicating a similar degree of technical difficulty for TF and VF deployment. [Copyright &y& Elsevier]

Background: The problem of obesity has risen to epidemic levels in the United States. A subset of patients with obesity will have metabolic syndrome. We sought to examine the impact of metabolic syndrome on the risk of morbidity and mortality among a large cohort of patients who underwent hepatic resection. Methods: Patients included in the National Surgical Quality Improvement Program (NSQIP) dataset who underwent hepatic resection between January 2005 and December 2008 were identified. Data on clinical characteristics, comorbidities, operative details, as well as postoperative complications and mortality were collected and analyzed. Patients with BMI >30 kg/m2 who also had hypertension and diabetes were defined as having metabolic syndrome. Results: A total of 3,973 patients who underwent a liver resection were identified. Overall mean body mass index was 28 kg/m2; 31.7% patients were obese (>30 kg/m2). Of the patients who were obese, 256 (20%) had metabolic syndrome. Patients with metabolic syndrome were less likely to have had a major hepatectomy (≥hemi-hepatectomy, 36% vs 43%; P = .01) but had a greater mean number of red blood cell transfusions (1.6 vs 1; P = .02). The incidence of postoperative complications after hepatectomy was 23%. Patients with metabolic syndrome had a greater risk for reintubation (odds ratio [OR] 1.9; P = .02), >48 hours ventilator dependence (OR 2.0; P = .003), myocardial infarction (OR 5.5; P = .01) and superficial surgical-site infections (OR 1.7; P = .02) compared with nonmetabolic patients. Overall postoperative mortality was 3%. Metabolic syndrome was associated with an increased risk of postoperative death (OR 2.7; P = .001). Conclusion: The presence of metabolic syndrome was associated with a greater risk of perioperative complications. In addition, patients with metabolic syndrome had greater than a 2-fold increased risk of death after hepatic resection. [Copyright &y& Elsevier]

Abstract: Purpose: To analyze a single-center experience with locally advanced pancreatic cancer (LAPC) patients treated with chemoradiation (CRT) and to evaluate predictive variables of outcome. Methods and Materials: LAPC patients at our institution between 1997 and 2009 were identified (n = 109). Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier analysis. Cox proportional hazard models were used to evaluate predictive factors for survival. Patterns of failure were characterized, and associations between local progression and distant metastasis were explored. Results: Median OS was 12.1 months (2.5-34.7 months) and median PFS was 6.7 months (1.1-34.7 months). Poor prognostic factors for OS include Karnofsky performance status ≤80 (P = .0062), treatment interruption (P = .0474), and locally progressive disease at time of first post-therapy imaging (P = .0078). Karnofsky performance status ≤80 (P = .0128), pretreatment CA19-9 >1000 U/mL (P = .0224), and treatment interruption (P = .0009) were poor prognostic factors for PFS. Both local progression (36%) and distant failure (62%) were common. Local progression was associated with a higher incidence of metastasis (P < .0001) and decreased time to metastasis (P < .0001). Conclusions: LAPC patients who suffer local progression following definitive CRT may experience inferior OS and increased risk of metastasis, warranting efforts to improve control of local disease. However, patients with poor pretreatment performance status, elevated CA19-9 levels, and treatment interruptions may experience poor outcomes despite aggressive management with CRT, and may optimally be treated with induction chemotherapy or supportive care. Novel therapies aimed at controlling both local and systemic progression are needed for patients with LAPC. [Copyright &y& Elsevier]

Introduction: Routine palliative bypass has been advocated for palliation of patients with pancreatic adenocarcinoma who have inoperable disease discovered at the time of surgery. We examined trends in the relative use of palliative bypass over time with an emphasis on identifying changes in surgical indications, type of bypass performed, as well as perioperative outcomes associated with surgical palliation.Methods: Between 1996 and 2010, 1,913 patients with pancreatic adenocarcinoma in the head of the pancreas were surgically explored. Data regarding preoperative symptoms, intraoperative findings, type of surgical procedure performed, as well as perioperative and long-term outcomes were collected and analyzed.Results: Of the 1,913 patients, 583 (30.5%) underwent a palliative procedure. Most patients presented with jaundice (72.2%). The majority of patients were evaluated by CT scan (97.4%), which revealed a median tumor size of 3.2 cm. Most patients who underwent surgical palliation (64.5%) had a double bypass, while a minority had either gastrojejunostomy (28.2%) or hepaticojejunostomy (7.2%) alone. While the number of pancreaticoduodenectomies remained relatively stable over time, there was a temporal decrease in the utilization of palliative bypass (P < 0.001). Unanticipated locally advanced disease vs. liver/peritoneal metastasis as the indication for palliative surgery also changed over time (1996-2001: 47.8% vs. 52.2%; 2002-2007: 49.2% vs. 50.8%; 2008-2010: 17.2% vs. 82.7%) (P = 0.005). Palliative failure rates were 2.3% after hepaticojejunostomy and 3.1% after grastrojejunostomy. Patients with unsuspected metastatic disease had a worse survival compared with patients who had locally unresectable disease (median survival: 5 vs. 8 months, respectively; HR = 1.43, P = 0.001).Conclusion: Palliative bypass procedures were less frequently performed over time, probably due to a significant decrease in the rate of unanticipated advanced locoregional disease at the time of exploration. While palliative bypass was effective, survival in the setting of metastatic disease was extremely short. [ABSTRACT FROM AUTHOR]

Objectives: This study was conducted to determine if pulmonary metastasectomy (PM) for isolated pancreatic cancer metastases is safe and effective.Methods: This was a retrospective case-control study of patients undergoing PM at our institution from 2000 to 2009 for isolated lung metastasis after resection for pancreatic cancer. Clinical and pathologic data were compared with a matched reference group. Resected neoplasms were immunolabeled for the Dpc4 protein. Kaplan-Meier analysis compared overall survival and survival after relapse.Results: Of 31 patients with isolated lung metastasis, 9 underwent 10 pulmonary resections. At initial pancreas resection, all patients were stage I or II. Other baseline characteristics were similar between the two groups. Median time from pancreatectomy to PM was 34 months (interquartile range 21-49). During the study, 29/31(90.6%) patients died. There were no in-hospital mortalities or complications after PM. Median cumulative survival was significantly improved in the PM group (51 vs. 23 months, p = 0.04). There was a trend toward greater 2-year survival after relapse in the PM group (40% vs. 27%, p = 0.2).Conclusions: In patients with isolated lung metastasis from pancreatic adenocarcinoma, this is the first study to show that pulmonary resection can be performed safely with low morbidity and mortality. The improved survival in the PM group may result in part from selection bias but may also represent a benefit of the procedure. [ABSTRACT FROM AUTHOR]

External beam radiation therapy procedures have, until recently, been planned almost exclusively using anatomic imaging methods. Molecular imaging using hybrid positron emission tomography (PET)/computed tomography scanning or single-photon emission computed tomography (SPECT) imaging has provided new insights into the precise location of tumors (staging) and the extent and character of the biologically active tumor volume (BTV) and has provided differential response information during and after therapy. In addition to the commonly used radiotracer 18F-fluoro- 2-deoxyD-glucose (FDG), additional radiopharmaceuticals are being explored to image major physiological processes as well as tumor biological properties, such as hypoxia, proliferation, amino acid accumulation, apoptosis, and receptor expression, providing the potential to target or boost the radiation dose to a biologically relevant region within a tumor, such as the most hypoxic or most proliferative area. Imaging using SPECT agents has furthered the possibility of limiting dose to functional normal tissues. PET can also portray the distribution of particle therapy by displaying activated species in situ. With both PET and SPECT imaging, fundamental physical issues of limited spatial resolution relative to the biological process, partial volume effects for quantification of small volumes, image misregistration, motion, and edge delineation must be carefully considered and can differ by agent or the method applied. Molecular imaging–guided radiation therapy (MIGRT) is a rapidly evolving and promising area of investigation and clinical translation. As MIGRT evolves, evidence must continue to be gathered to support improved clinical outcomes using MIGRT versus purely anatomic approaches. [ABSTRACT FROM AUTHOR]

Background: To examine the effect of body mass index (BMI) on clinicopathologic factors and long-term survival in patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma.Methods: Data on BMI, weight loss, operative details, surgical pathology, and long-term survival were collected on 795 patients who underwent pancreaticoduodenectomy. Patients were categorized as obese (BMI > 30 kg/m(2)), overweight (BMI 25 to <30 kg/m(2)), or normal weight (BMI < 25 kg/m(2)) and compared using univariate and multivariate analyses.Results: At the time of surgery, 14% of patients were obese, 33% overweight, and 53% normal weight. Overall, 32% of patients had preoperative weight loss of >10%. There were no differences in operative times among the groups; however, higher BMI was associated with increased risk of blood loss (P < 0.001) and pancreatic fistula (P = 0.01). On pathologic analysis, BMI was not associated with tumor stage or number of lymph nodes harvested (both P > 0.05). Higher BMI patients had a lower incidence of a positive retroperitoneal/uncinate margin versus normal weight patients (P = 0.03). Perioperative morbidity and mortality were similar among the groups. Obese and overweight patients had better 5-year survival (22% and 22%, respectively) versus normal weight patients (15%; P = 0.02). After adjusting for other prognostic factors, as well as preoperative weight loss, higher BMI remained independently associated with improved cancer-specific survival (overweight: hazard ratio, 0.68; obese: hazard ratio, 0.72; both P < 0.05).Conclusion: Obese patients had similar tumor-specific characteristics, as well as perioperative outcomes, compared with normal weight patients. However, obese patients undergoing pancreaticoduodenectomy for pancreatic cancer had an improved long-term survival independent of known clinicopathologic factors. [ABSTRACT FROM AUTHOR]

The article discusses reports on the development and review of the American College of Radiology (ACR) Appropriateness Criteria (AC) published within the issue.

Background: Whether ampullary neoplasms are best surgically managed by pancreaticoduodenectomy versus local ampullectomy is controversial. We sought to examine the outcome of patients undergoing pancreaticoduodenectomy versus ampullectomy, as well as to identify factors predictive of lymph node metastasis in patients with ampullary neoplasms.Methods: Between 1970 and 2007, 450 patients who underwent surgical resection of ampullary adenoma or adenocarcinoma were identified from a prospective, single-institution database. Data on clinicopathologic factors, morbidity, mortality, and survival were analyzed.Results: The initial surgical procedure was pancreaticoduodenectomy in 96.7% patients and ampullectomy in 3.3%. Final diagnosis was invasive adenocarcinoma (77.1%) or adenoma (22.9%). Median tumor size was similar for adenomas associated with an adenocarcinoma (2.5 cm) versus adenomas without invasive cancer (2.9 cm; P=0.71). Morbidity was comparable with pancreaticoduodenectomy (52.2%) versus ampullectomy (33.3%; P=0.15), as was 30-day mortality (pancreaticoduodenectomy, 2.1% versus ampullectomy, 0%; P=0.6). Metastatic disease to regional lymph nodes was present in 54.5% patients with adenocarcinoma. Factors associated with presence of lymph node metastasis included tumor size > or = 1 cm (OR 2.1), poor histologicgrade (OR 4.8), perineural invasion (OR 3.0), microscopic vessel invasion (OR 6.6), and depth of invasion > pT1 (OR 4.3; all P<0.05). Specifically, risk of lymph node metastasis increased with T stage (T1, 28.0%; T2, 50.9%; T3, 71.7%; T4, 77.3%; P<0.001).Conclusion: When surgery is indicated, radical resection is required for early invasive adenocarcinoma of the ampulla of Vater, as lymph node metastases are present in nearly 30% of patients with T1 disease. Pancreaticoduodenectomy should be the preferred approach for most ampullary neoplasms that require surgical resection. [ABSTRACT FROM AUTHOR]

Summary: Pancreatic adenosquamous carcinoma is a rare morphological variant of pancreatic adenocarcinoma with an especially poor prognosis. The purpose of this study is to identify clinicopathologic features associated with prognosis, assess whether the percentage of squamous differentiation in pancreatic adenosquamous carcinoma is associated with an inferior prognosis, and examine the impact of adjuvant chemoradiation therapy on overall survival. Forty-five (1.2%) of 3651 patients who underwent pancreatic resection at the Johns Hopkins Hospital, Baltimore, MD, between 1986 and 2007 were identified with adenocarcinoma of the pancreas with any squamous differentiation. All pathologic specimens were re-reviewed. Statistical analyses were performed on the 38 patients amenable to adjuvant chemoradiation therapy for whom clinical outcome data could be obtained. Median age was 68 years (61% male). Sixty-one percent underwent pancreaticoduodenectomy. Median tumor size was 5.0 cm. Seventy-six percent of carcinomas were node positive, 37% were margin-positive resections, and 68% had 30% or more squamous differentiation. Median overall survival of the pancreatic adenosquamous carcinoma cohort was 10.9 months (range, 2.1-140.6 months; 95% confidence interval, 8.2-12.5 months). Adjuvant chemoradiation therapy was associated with superior overall survival in patients with pancreatic adenosquamous carcinoma (P = .005). Adjuvant chemoradiation therapy was associated with improved survival in patients with tumors 3 cm or larger and vascular or perineural invasion (P = .02, .03, .02, respectively). The proportion of squamous differentiation was not associated with median overall survival (<30% versus ≥30%, P = .82). Survival after pancreatic resection of pancreatic adenosquamous carcinoma is poor. Treatment with adjuvant chemoradiation therapy is associated with improved survival. The proportion of squamous differentiation in resected pancreatic adenosquamous carcinoma specimens does not appear to impact overall survival. [Copyright &y& Elsevier]

Background: There are limited data on patterns of recurrence and factors associated with local recurrence following pancreaticoduodenectomy for pancreatic adenocarcinoma and adjuvant 5-flurouracil-based chemoradiation therapy.Methods and Materials: Between 1995 and 2005, 905 patients underwent pancreaticoduodenectomy for pancreatic adenocarcinoma; 154 patients had complete pattern of recurrence data available.Results: At median follow-up of 20.2 months, 103 (66.9%) patients recurred with median time to recurrence of 16.2 months. Most patients recurred with distant disease only (68.9%), while 21.4% patients recurred with local disease only; ten (9.7%) patients recurred with local and distant disease. Several factors were associated with local recurrence: poor tumor differentiation (hazards ration [HR] 2.39) and presence of metastatic lymph nodes (HR 1.89, both p < 0.05). Among N1 patients, poor tumor differentiation (HR 3.92), >5 metastatic LN (HR 3.75), and lymph node ratio (LNR) >0.4 (HR 2.96) had the highest risk of local recurrence (all p < 0.05). Increasing LNR was associated with an incremental increased risk of local recurrence (LNR <0.2, 21.3% versus LNR >or=0.2 to 0.4, 25.2% versus LNR >0.4, 40.4%; p < 0.05).Conclusions: Although most patients who receive standard 5-flurouracil-based chemoradiation therapy will ultimately succumb to distant disease, about 30% recur locally. Poor tumor differentiation, a high number of metastatic LN (>5), and LNR >0.4 are associated with the highest risk of local failure. In these patients, radiation dose escalation and/or a combination of radiation with novel chemotherapeutic agents may be necessary to improve outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To compare transarterial chemoembolization (CE) versus yttrium-90 (90Y) radioembolization (RE) for liver-dominant metastatic colorectal adenocarcinoma as salvage therapy. Materials and Methods: Of 36 patients, 21 underwent CE (37 procedures; 11 men; mean age, 67 years; 16 with Child-Pugh class A disease) and 15 underwent 90Y RE (19 procedures; 11 men; mean age, 64 years; 13 with Child-Pugh class A disease) for liver-dominant colorectal adenocarcinoma. Mean index dominant lesion sizes were 9.3 cm and 8.2 cm in the CE and RE groups, respectively. Multilobar disease was seen in 67% and 87% of the respective groups, and extrahepatic metastases were seen in 43% and 33%, respectively. Mean times from diagnosis of liver metastasis to CE or RE were 17.6 months and 22.6 months, respectively. Results: A total of 37 CE procedures with cisplatin, doxorubicin, and mitomycin were performed, and 19 RE procedures with 90Y were performed; 43% of patients in the CE group and 20% in the RE group received multiple treatment sessions, and 100% of procedures were technically successful. Median survival times were 7.7 months for the CE group and 6.9 months for the RE group (P = .27). The 1-, 2-, and 5-year survival rates were 43%, 10%, and 0%, respectively, in the CE group; and 34%, 18%, and 0%, respectively, in the RE group. There was one major complication (2.7%) in the CE group (pulmonary embolism), with a 30-day mortality rate of 5.4% (n = 2). There were no major complications in the RE group, with a 30-day mortality rate of 5.2% (n = 1). Conclusions: Patients with unresectable liver colorectal metastases that progress despite systemic chemotherapy can undergo palliative treatment with CE or RE with similar survival benefit. [Copyright &y& Elsevier]

Background: No data on incidence, management, or natural history of chyle leaks following pancreatic resection have been published. We sought to identify possible risk factors associated with chyle leaks following pancreatic resection, as well as determine the natural history of this rare complication.Methods: Between 1993 and 2008, 3,532 patients underwent pancreatic resection at a single institution. Data on demographics, operative details, primary tumor status, and chyle leak were collected. To identify risk factors associated with chyle leak, a matched 3:1 paired analysis was performed.Results: Of 3,532 patients undergoing pancreatic resection, 47 (1.3%) developed a chyle leak (n = 34, contained chyle leak versus n = 13, diffuse chylous ascites). Chyle leak was identified at median 5 days following surgery. Median drain triglyceride levels were 592 ng/dl. After matching on tumor size, disease etiology, and resection type, the number of lymph nodes harvested and history of concomitant vascular resection predicted higher risk of chyle leak (both P < 0.05). Total parenteral nutrition (TPN) was required in more patients with chylous ascites (92.3%) than those with chyle leaks (44.1%) (P = 0.003). The median time to resolution was shorter for contained chyle leaks (13 days) versus chylous ascites (36 days) (P < 0.001). Patients with chylous ascites tended to have shorter overall survival (3-year, 18.8%) versus patients with no chyle leak (3-year, 46.9%) (P = 0.12). In contrast, patients with a contained chyle leak had a similar survival as patients with no chyle leak (3-year, 53.4% versus 46.9%, respectively) (P = 0.32).Conclusion: Chyle leak was a rare (1.3%) complication following pancreatic resection that was associated with number of lymph nodes harvested and concomitant vascular resection. In general, chyle leaks were successfully managed with TPN with no adverse impact on outcome. Patients with chylous ascites, however, had a more protracted clinical course and tended to have a worse long-term survival. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Bowen’s disease (BD), a form of squamous cell carcinoma in situ, can transform into invasive squamous cell carcinoma and should be treated aggressively. Although standard treatment for BD is electrodessication and curettage, radiotherapy (RT) can be used for those patients who are poor surgical candidates or when surgery could result in a poor cosmetic and functional outcome. Surgical treatment of BD of the digit can result in poor function and sometimes amputation. Here, we report our experience using a unique water bath technique to treat BD of the digit. Materials and methods: This retrospective review evaluates the outcomes and toxicity of nine consecutive patients with BD of the digit treated with RT between 1999 and 2004. Fourteen digit lesions were immersed in a water bath and treated with photon irradiation. The median radiation dose delivered was 50Gy (range 25–66Gy) in 2.5Gy fractions (range 2–3Gy). Results: The median age of the patients treated was 77 years (range 29–87 years). Three patients (33%) had more than one digit treated. With a median follow-up of 25 months (range 0.4–52 months), all 14 digit lesions are locally controlled. The majority of lesions demonstrated mild to moderate erythema, desquamation, or edema (grade 1–2) acutely following RT which resolved within one month of treatment. Two digits (14%) developed ulcers (grade 4) which healed following RT. The only long-term toxicity was decreased sensation and strength in one patient who had three circumferential lesions. This toxicity was limited and did not appear to influence the patient’s daily activities (grade 2). Conclusions: These preliminary results demonstrate high rates of tumor control with minimal morbidity following definitive RT in the treatment of BD of the digit, and suggest that RT may be a viable treatment alternative to surgery for selected lesions. Through a multidisciplinary assessment, treatment of BD of the digit can be individualized to optimize patient care. [Copyright &y& Elsevier]

Objectives: To assess, in a Phase I study, whether bladder preservation with concurrent gemcitabine and radiotherapy (RT) influenced patient-reported quality of life (QOL) as determined by the Functional Assessment of Cancer Therapy-Bladder (FACT-BL).Methods: Between January 1998 and March 2002, 24 patients with urothelial carcinoma of the bladder were enrolled, and 23 patients underwent transuretheral resection of bladder tumor, followed by twice-weekly gemcitabine with concurrent RT. The initial dose was 10 mg/m2 given twice weekly and increased as tolerated. To assess treatment-related QOL, patients completed the FACT-BL questionnaire.Results: Of the 24 patients enrolled, 23 (96%) were assessed for toxicity and response. The FACT-generic (G) QOL assessment was obtained from 22 (92%) of 23 patients. No statistically significant difference was found in the FACT-G or FACT-BL or the combination before, during, or after treatment. The FACT-BL values were lower in patients who received higher doses of gemcitabine (greater than 20 mg/m2 versus 20 mg/m2 or less). At least one dose-limiting toxicity (DLT) was experienced by 5 (23%) of 22 patients. The FACT-G values were lower for those patients who experienced DLT (difference of -13.1, P = 0.07). The physical well-being scores for patients who experienced DLT were lower after treatment (difference of -5.2, P = 0.03) compared with those without DLT.Conclusions: Concurrent RT and gemcitabine failed to statistically influence patient-reported QOL, although patients who received higher doses reported lower FACT-BL scores. The results of this study suggest that concurrent gemcitabine with conformal RT is a tolerable treatment regimen for bladder preservation, as demonstrated by the excellent treatment compliance and similar FACT measurements. [Copyright &y& Elsevier]

: PurposeStereotactic radiosurgery (SRS) has become a minimally invasive treatment modality for patients with refractory trigeminal neuralgia. It is unclear, however, how best to treat patients with pain that is refractory or recurrent after initial SRS. We report on treatment outcomes and quality of life for patients treated with repeated SRS for refractory or recurrent trigeminal neuralgia.: Methods and materialsBetween June 1996 and June 2001, 112 patients with trigeminal neuralgia were treated with SRS at the University of Maryland Medical Center. Eighteen patients underwent repeat SRS 3–42 months (median, 8 months) after initial radiosurgery because of unsatisfactory or unsustained pain relief. Patients received a median prescription dose of 75 and 70 Gy, respectively, for the first and second treatments. Self-reports of pain control were assessed with a standard questionnaire containing the complete Barrow Neurologic Institute Pain Scale.: ResultsThe median follow-up was 37.5 months (range, 12–68 months) after initial SRS and 24.5 months (range, 6–65 months) after repeat SRS. For the 18 patients in this series, the percentage of patients reporting excellent, good, fair, and poor responses after the initial and repeat SRS was 50%, 28%, 6%, and 16% and 45%, 33%, 0%, and 22%, respectively. None of the 3 patients with pain refractory to initial SRS responded to repeat SRS. Among those with recurrent pain after initial SRS, 14 patients (93%) achieved excellent or good pain outcomes after repeat SRS. The actuarial analysis revealed a 1-year recurrence rate of 22%, with no patients reporting recurrent pain after 9 months of follow-up. Two patients (11%) reported new or increased facial numbness after retreatment, which was described as bothersome by one. Repeat SRS resulted in a median 60% improvement in quality of life, and 56% of patients believed that the procedure was successful.: ConclusionDespite a modest dose reduction, repeat SRS provided similar rates of complete pain control as the initial procedure, but was not effective for patients with no response to initial treatment. Repeat SRS was more efficacious for those patients who experienced longer periods of pain relief after the initial SRS. The incidence of complications was not significantly different from that observed for initial SRS. In this series, most patients had significant improvements in quality of life. [Copyright &y& Elsevier]