Development of an Objective Scoring System for Endoscopic Assessment of Radiation-Induced Upper Gastrointestinal Toxicity.

We developed and implemented an objective toxicity scoring system to be used during endoscopic evaluation of the upper gastrointestinal (GI) tract in order to directly assess changes in toxicity during the radiation treatment of pancreatic cancer. We assessed and validated the upper GI toxicity of 19 locally advanced pancreatic cancer trial patients undergoing stereotactic body radiation therapy (SBRT). Wilcoxon-signed rank tests were used to compare pre- and post-SBRT scores. Comparison of the toxicity scores measured before and after SBRT revealed a mild increase in toxicity in the stomach and duodenum (p < 0.005), with no cases of severe toxicity observed. Kappa and AC1 statistics analysis were used to evaluate interobserver agreement. Our toxicity scoring system was reliable in determining GI toxicity with a good overall interobserver agreement for pre-treatment scores (stomach, κ = 0.71, p < 0.005; duodenum, κ = 0.88, p < 0.005) and post-treatment scores (stomach, κ = 0.71, p < 0.005; duodenum, κ = 0.76, p < 0.005). The AC1 statistics yielded similar results. With future usage, we hope this scoring system will be a useful tool for objectively and reliably assessing changes in GI toxicity during the treatment of pancreatic cancer and for GI toxicity assessments and comparisons during radiation therapy research trials.

Exploring the patient experience of locally advanced or metastatic pancreatic cancer to inform patient-reported outcomes assessment.

PURPOSE: Pancreatic cancer and its treatments impact patients' symptoms, functioning, and quality of life. Content-valid patient-reported outcome (PRO) instruments are required to assess outcomes in clinical trials. This study aimed to: (a) conceptualise the patient experience of pancreatic cancer; (b) identify relevant PRO instruments; (c) review the content validity of mapped instruments to guide PRO measurement in clinical trials. METHODS: Qualitative literature and interviews with clinicians and patients were analysed thematically to develop a conceptual model of patient experience. PRO instruments were reviewed against the conceptual model to identify gaps in measurement. Cognitive debriefing explored PRO conceptual relevance and patients' understanding. RESULTS: Patients in the USA (N = 24, aged 35-84) and six clinicians (from US and Europe) were interviewed. Pre-diagnosis, pain was the most frequently reported symptom (N = 21). Treatments included surgery, radiation, chemotherapy, and immunotherapy. Surgery was associated with acute pain and gastrointestinal symptoms. Chemotherapy/chemoradiation side effects were cyclical and included fatigue/tiredness (N = 21), appetite loss (N = 15), bowel problems (N = 15), and nausea/vomiting (N = 15). Patients' functioning and well-being were impaired. The literature review identified 49 PRO measures; the EORTC QLQ-C30/PAN26 were used most frequently and mapped with interview concepts. Patients found the EORTC QLQ-C30/PAN26 to be understandable and relevant; neuropathic side effects were suggested additions. CONCLUSIONS: This is the first study to develop a conceptual model of patients' experience of metastatic/recurrent pancreatic cancer and explore the content validity of the EORTC QLQ-C30/PAN26 following therapeutic advances. The EORTC QLQ-C30/PAN26 appears conceptually relevant; additional items to assess neuropathic side effects are recommended. A recall period should be stated throughout to standardise responses.

Assessing the Financial Burden Associated With Treatment Options for Resectable Pancreatic Cancer.

OBJECTIVE: The aim of this study is to assess the financial burden associated with treatment options for resectable pancreatic cancer. BACKGROUND: As the volume of cancer care increases in the United States, there is growing interest among both clinicians and policy-makers to reduce its financial impact on the healthcare system. However, costs relative to the survival benefit for differing treatment modalities used in practice have not been described. METHODS: Patients undergoing resection for pancreatic cancer were identified in the Truven Health MarketScan database. Associations between chemoradiation therapies and survival were performed using parameterized multivariable accelerated failure time models. Median payments over time were calculated for surgery, chemoradiation, and subsequent hospitalizations. RESULTS: A total of 2408 patients were included. Median survival among all patients was 21.1 months [95% confidence interval (CI): 19.8-22.5 months], whereas median follow-up time was 25.1 months (95% CI: 23.5-26.5 months). After controlling for comorbidity, receipt of neoadjuvant therapy, and nodal involvement, a longer survival was associated with undergoing combination gemcitabine and nab-paclitaxel [time ratio (TR) = 1.26, 95% CI: 1.02-1.57, P = 0.035) or capecitabine and radiation (TR = 1.25, 95% CI: 1.04-1.51, P = 0.018). However, median cumulative payments for gemcitabine with nab-paclitaxel were highest overall [median $74,051, interquartile range (IQR): $38,929-$133,603). CONCLUSIONS: Total payments for an episode of care relative to improvement in survival vary significantly by treatment modality. These data can be used to inform management decisions about pursuing further care for pancreatic cancer. Future investigations should seek to refine estimates of the cost-effectiveness of different treatments.

Computed tomography imaging assessment of postexternal beam radiation changes of the liver.

Radiation is being used for patients with primary and secondary liver cancers, as a rapidly evolving treatment. However, postradiation imaging changes of the liver are not well understood and therefore challenging to interpret. Distinguishing normal radiation changes from residual or recurrent disease is difficult. Size and contrast enhancement have been used to guide interpretation and clinical recommendations, but normal radiation changes can make interpretation difficult and are not accounted for in available guidelines. Knowledge of dose- and time-dependent changes in addition to imaging findings, such as morphological and enhancement patterns, provides useful differentiating parameters. This paper reviews recent studies using computed tomography that can guide interpretation and help differentiate tumor from benign changes after external beam radiation.

Race-based differences in length of stay among patients undergoing pancreatoduodenectomy.

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.

Influence of patient, physician, and hospital factors on 30-day readmission following pancreatoduodenectomy in the United States.

UNLABELLED: IMPORTANCE It is not known whether hospital and surgeon volumes have an association with readmission among patients undergoing pancreatoduodenectomy. OBJECTIVE: To evaluate patient-, surgeon-, and hospital-level factors associated with readmission. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare data with cases diagnosed from January 1, 1998, to December 31, 2005, and followed up until December 2007. Population-based cancer registry data were linked to Medicare data for the corresponding patients. A total of 1488 unique individuals who underwent a pancreatoduodenectomy were identified. INTERVENTIONS: Undergoing pancreatoduodenectomy at hospitals classified by volume of pancreatoduodenectomy procedures performed at the facility were either very-low, low, medium, or high volume. Undergoing pancreatoduodenectomy by surgeons classified by volume of pancreatoduodenectomy procedures performed by the surgeon were either very-low, low, medium, or high volume. MAIN OUTCOMES AND MEASURES: In-hospital morbidity, mortality, and 30-day readmission were examined. RESULTS: The median age was 74 years, and 1436 patients (96.5%) had a least 1 medical comorbidity. Patients were treated by 575 distinct surgeons at 298 distinct hospitals. Length of stay was longest (median, 17 days) and 90-day mortality highest (17.2%) at very-low-volume hospitals (P < .001). Among all pancreatoduodenectomy patients, 292 (21.3%) were readmitted within 30 days of discharge. There was no effect of surgeon volume and a modest effect of hospital volume (odds ratio for highest- vs lowest-volume quartiles, 1.85; 95% CI, 1.22-2.80; P = .02). The presence of significant preoperative medical comorbidities was associated with an increased risk for hospital readmission after pancreatoduodenectomy. A comorbidity score greater than 13 had a pronounced effect on the chance of readmission following pancreatoduodenectomy (odds ratio, 2.06; 95% CI, 1.56-2.71; P < .001). The source of variation in readmission was primarily attributable to patient-related factors (95.4%), while hospital factors accounted for 4.3% of the variability and physician factors for only 0.3%. CONCLUSIONS AND RELEVANCE: Nearly 1 in 5 patients are readmitted following pancreatoduodenectomy. While variation in readmission is, in part, attributable to differences among hospitals, the largest share of variation was found at the patient level.

Feasibility and value of PatientViewpoint: a web system for patient-reported outcomes assessment in clinical practice.

BACKGROUND: The PatientViewpoint website collects patient-reported outcomes and links them with the electronic health record to aid patient management. This pilot test evaluated PatientViewpoint's use, usefulness, and acceptability to patients and clinicians. METHODS: This was a single-arm prospective study that enrolled breast and prostate cancer patients undergoing treatment and the clinicians who managed them. Patients completed patient-reported outcomes every 2 weeks, and clinicians could access the results for patient visits. Scores that were poor relative to norms or substantially worse than the previous assessment were highlighted. After three on-study visits, we assessed patient and clinician perspectives on PatientViewpoint using close-ended and open-ended questions. RESULTS: Eleven out of 12 eligible clinicians (92%) and 52/76 eligible patients (68%) enrolled. Patients completed a median of 71% of assigned questionnaires; clinicians reported using the information for 79% of patients, most commonly as a source of additional information (51%). At the median, score reports identified three potential issues, of which 1 was discussed during the visit. Patients reported the system was easy to use (92%), useful (70%), aided recall of symptoms/side effects (72%), helped them feel more in control of their care (60%), improved discussions with their provider (49%), and improved care quality (39%). Patients and clinicians desired more information on score interpretation and minor adjustments to site navigation. CONCLUSIONS: These results support the feasibility and value of PatientViewpoint. An ongoing study is using a continuous quality improvement approach to further refine PatientViewpoint. Future studies will evaluate its impact on patient care and outcomes.

Patient readmission and mortality after surgery for hepato-pancreato-biliary malignancies.

BACKGROUND: The incidence and associated risk factors for readmission after hepato-pancreato-biliary surgery are poorly characterized. The objective of the current study was to compare readmission after pancreatic vs hepatobiliary surgical procedures, as well as to identify potential factors associated with higher readmission within 30 days of discharge. STUDY DESIGN: Using Surveillance, Epidemiology and End Results-Medicare linked data from 1986-2005, we identified 9,957 individuals aged 66 years and older who underwent complex hepatic, biliary, or pancreatic procedures for cancer treatment and were eligible for analysis. In-hospital morbidity, mortality, and 30-day readmission were examined. RESULTS: Primary surgical treatment consisted of a pancreatic (46.7%), hepatic (50.0%), or biliary (3.4%) procedure. Mean patient age was 72.6 years and most patients were male (53.2%). The number of patients with multiple preoperative comorbidities increased over time (patients with Elixhauser's comorbidity score >13: 1986-1990, 47.0% vs 2001-2005, 62.9%; p < 0.001). Pancreatic operations had higher inpatient mortality vs hepatobiliary procedures (9.2% vs 7.3%; p < 0.001). Mean length of stay after pancreatic procedures was longer compared with hepatobiliary procedures (19.7 vs 10.3 days; p < 0.001). The proportion of patients readmitted after a pancreatic (1986-1990, 17.7%; 1991-1995, 16.1%; 1996-2000, 18.6%; 2001-2005, 19.6%; p = 0.15) or hepatobiliary (1986-1990, 14.3%; 1991-1995, 14.1%; 1996-2000, 15.2%; 2001-2005, 15.5%; p = 0.69) procedure did not change over time. Factors associated with increased risk of readmission included preoperative Elixhauser comorbidities >13 (odds ratio = 1.90) and prolonged index hospital stay ≥10 days (odds ratio = 1.54; both p < 0.05). During the readmission, additional morbidity and mortality were 46.5% and 8.0%, respectively. CONCLUSIONS: Although the incidence of readmission did not change across the time periods examined, readmission was higher among patients undergoing a pancreatic procedure vs a hepatobiliary procedure. Other factors associated with risk of readmission included number of patient comorbidities and prolonged hospital stay. Readmission was associated with additional short-term morbidity and mortality.

Incidence and management of chyle leaks following pancreatic resection: a high volume single-center institutional experience.

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.

Prospective quality-of-life assessment in patients receiving concurrent gemcitabine and radiotherapy as a bladder preservation strategy.

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.

Repeat gamma knife radiosurgery for refractory or recurrent trigeminal neuralgia: treatment outcomes and quality-of-life assessment.

PURPOSE: Stereotactic 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 MATERIALS: Between 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. RESULTS: The 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. CONCLUSION: Despite 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.