Samuel J Wang

Publications of Samuel J Wang

• Nomogram for predicting the benefit of adjuvant chemoradiotherapy for resected gallbladder cancer.

  Authors: Samuel J Wang, Andrew Lemieux, Jayashree Kalpathy-Cramer, Celine B Ord, Gary V Walker, C David Fuller, Jong-Sung Kim, Charles R Thomas

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 11/2011; 29(35):4627-32.

  Although adjuvant chemoradiotherapy for resected gallbladder cancer may improve survival for some patients, identifying which patients will benefit remains challenging because of the rarity of thisAlthough adjuvant chemoradiotherapy for resected gallbladder cancer may improve survival for some patients, identifying which patients will benefit remains challenging because of the rarity of this disease. The specific aim of this study was to create a decision aid to help make individualized estimates of the potential survival benefit of adjuvant chemoradiotherapy for patients with resected gallbladder cancer. Patients with resected gallbladder cancer were selected from the Surveillance, Epidemiology, and End Results (SEER) -Medicare database who were diagnosed between 1995 and 2005. Covariates included age, race, sex, stage, and receipt of adjuvant chemotherapy or chemoradiotherapy (CRT). Propensity score weighting was used to balance covariates between treated and untreated groups. Several types of multivariate survival regression models were constructed and compared, including Cox proportional hazards, Weibull, exponential, log-logistic, and lognormal models. Model performance was compared using the Akaike information criterion. The primary end point was overall survival with or without adjuvant chemotherapy or CRT. A total of 1,137 patients met the inclusion criteria for the study. The lognormal survival model showed the best performance. A Web browser-based nomogram was built from this model to make individualized estimates of survival. The model predicts that certain subsets of patients with at least T2 or N1 disease will gain a survival benefit from adjuvant CRT, and the magnitude of benefit for an individual patient can vary. A nomogram built from a parametric survival model from the SEER-Medicare database can be used as a decision aid to predict which gallbladder patients may benefit from adjuvant CRT.

• Individualized estimation of conditional survival for patients with head and neck cancer.

  Authors: Samuel J Wang, Amanda R Wissel, Celine B Ord, Jayashree Kalpathy-Cramer, C David Fuller, John M Holland, Neil D Gross

  Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 03/2011; 145(1):71-3.

  Survival for cancer patients is usually only reported as survival from time of diagnosis. For patients who survive 1 or more years after diagnosis, however, survival probability changes over time andSurvival for cancer patients is usually only reported as survival from time of diagnosis. For patients who survive 1 or more years after diagnosis, however, survival probability changes over time and is more accurately depicted by conditional survival. The specific aim of this project was to build a survival regression model and Web-based tool to make individualized estimates of conditional survival for patients with head and neck cancer based on tumor and patient characteristics. Using data from the Surveillance, Epidemiology, and End Results (SEER) database, a prediction modeling tool was built that can estimate prognosis for patients with head and neck cancer who have already survived a period of time after diagnosis. Having more accurate prognostic information may empower both patients and clinicians to make more appropriate decisions regarding follow-up, surveillance testing, and future treatment.

• Prospective randomized double-blind pilot study of site-specific consensus atlas implementation for rectal cancer target volume delineation in the cooperative group setting.

  Authors: Clifton D Fuller, Jasper Nijkamp, Joop C Duppen, Coen R N Rasch, Charles R Thomas, Samuel J Wang, Paul Okunieff, William E Jones, Daniel Baseman, Shilpen Patel [......] Benjamin D Smith, Alan W Katz, Camille McGann, Jennifer L Harper, Daniel T Chang, Stephen Smalley, David T Marshall, Karyn A Goodman, Niko Papanikolaou, Lisa A Kachnic

  International journal of radiation oncology, biology, physics. 02/2011; 79(2):481-9.

  Variations in target volume delineation represent a significant hurdle in clinical trials involving conformal radiotherapy. We sought to determine the effect of a consensus guideline-based visualVariations in target volume delineation represent a significant hurdle in clinical trials involving conformal radiotherapy. We sought to determine the effect of a consensus guideline-based visual atlas on contouring the target volumes. A representative case was contoured (Scan 1) by 14 physician observers and a reference expert with and without target volume delineation instructions derived from a proposed rectal cancer clinical trial involving conformal radiotherapy. The gross tumor volume (GTV), and two clinical target volumes (CTVA, including the internal iliac, presacral, and perirectal nodes, and CTVB, which included the external iliac nodes) were contoured. The observers were randomly assigned to receipt (Group A) or nonreceipt (Group B) of a consensus guideline and atlas for anorectal cancers and then instructed to recontour the same case/images (Scan 2). Observer variation was analyzed volumetrically using the conformation number (CN, where CN = 1 equals total agreement). Of 14 evaluable contour sets (1 expert and 7 Group A and 6 Group B observers), greater agreement was found for the GTV (mean CN, 0.75) than for the CTVs (mean CN, 0.46-0.65). Atlas exposure for Group A led to significantly increased interobserver agreement for CTVA (mean initial CN, 0.68, after atlas use, 0.76; p = .03) and increased agreement with the expert reference (initial mean CN, 0.58; after atlas use, 0.69; p = .02). For the GTV and CTVB, neither the interobserver nor the expert agreement was altered after atlas exposure. Consensus guideline atlas implementation resulted in a detectable difference in interobserver agreement and a greater approximation of expert volumes for the CTVA but not for the GTV or CTVB in the specified case. Visual atlas inclusion should be considered as a feature in future clinical trials incorporating conformal RT.

• An interactive tool for individualized estimation of conditional survival in rectal cancer.

  Authors: Samuel J Wang, Amanda R Wissel, Join Y Luh, C David Fuller, Jayashree Kalpathy-Cramer, Charles R Thomas

  Annals of surgical oncology. 01/2011; 18(6):1547-52.

  For rectal cancer patients who have already survived a period of time after diagnosis, survival probability changes and is more accurately depicted by conditional survival. The specific aim of thisFor rectal cancer patients who have already survived a period of time after diagnosis, survival probability changes and is more accurately depicted by conditional survival. The specific aim of this study was to develop an interactive tool for individualized estimation of changing prognosis for rectal cancer patients. A multivariate Cox proportional hazards (CPH) survival model was constructed using data from rectal cancer patients diagnosed from 1994 to 2003 from the Surveillance, Epidemiology, and End Results (SEER) database. Age, race, sex, and stage were used as covariates in the survival prediction model. The primary outcome variable was overall survival conditional on having survived up to 5 years from diagnosis. Data from 42,830 rectal cancer patients met the inclusion criteria. The multivariate CPH model showed age, race, sex, and stage as significant independent predictors of survival. The survival prediction model demonstrated good calibration and discrimination, with a bootstrap-corrected concordance index of 0.75. A web-based prediction tool was built from this regression model that can compute individualized estimates of changing prognosis over time. An interactive prediction modeling tool can estimate prognosis for rectal cancer patients who have already survived a period of time after diagnosis and treatment. Having more accurate prognostic information can empower both patients and clinicians to be able to make more appropriate decisions regarding follow-up, surveillance testing, and future treatment.

• Conditional survival and the choice of conditioning set for patients with colon cancer: an analysis of NSABP trials C-03 through C-07.

  Authors: Beth A Zamboni, Greg Yothers, Mehee Choi, Clifton D Fuller, James J Dignam, Peter C Raich, Charles R Thomas, Michael J O'Connell, Norman Wolmark, Samuel J Wang

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 05/2010; 28(15):2544-8.

  Colon cancer overall survival (OS) is usually computed from the time of diagnosis. Survival gives the initial prognosis but does not reflect how prognosis changes with changing hazard rates overColon cancer overall survival (OS) is usually computed from the time of diagnosis. Survival gives the initial prognosis but does not reflect how prognosis changes with changing hazard rates over time. Conditional survival (probability of surviving y additional years given they have survived x years [CS or OS|OS]) is an alternative measure that accounts for elapsed time since diagnosis, providing more relevant prognostic information. We extend the concept of CS to condition on the set of patients alive, recurrence-free, and second primary cancer-free (disease-free survival [OS|DFS]). Using data from National Surgical Adjuvant Breast and Bowel Project trials C-03 through C-07, 5-year OS|DFS was calculated on patients who were disease free up to 5 years after diagnosis, stratified by age, stage, nodal status, and performance status (PS). For stage II, OS|DFS improved from 87% to 92% at 5 years. For stage III, OS|DFS improved from 69% to 88%. Patients younger than 50 years showed OS|DFS improvement from 79% to 95%; those older than 70 years showed no sustained increase in OS|DFS. Node-negative patients with > or = 12 nodes resected showed little change (89% to 94%); those with more than four positive nodes showed an improvement (57% to 86%). Patients with a PS of 0 or 1 demonstrated a small improvement; those with a PS of 2 did not (64% to 58%). Prognosis improves over time for almost all groups of patients with colon cancer, especially those with positive nodes. OS|DFS is a more relevant measure of prognosis for those who have already survived disease free a period of time after diagnosis.

• Parametric survival models for predicting the benefit of adjuvant chemoradiotherapy in gallbladder cancer.

  Authors: Samuel J Wang, Jayashree Kalpathy-Cramer, Jong Sung Kim, C David Fuller, Charles R Thomas

  AMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium. 01/2010; 2010:847-51.

  The Cox proportional hazards model is the most commonly used survival model in oncology; however, this semi-parametric model may not be the most appropriate survival model when the proportionalityThe Cox proportional hazards model is the most commonly used survival model in oncology; however, this semi-parametric model may not be the most appropriate survival model when the proportionality assumption does not hold. In this study, we consider the use of several types of accelerated failure time parametric survival techniques for modeling the benefit of adjuvant chemoradiotherapy for gallbladder cancer. In comparing the Weibull, exponential, log-logistic, and log-normal models, we found that the log-normal had the most favorable Akaike Information Criterion, and additional analyses of this model indicated that our gallbladder cancer dataset exhibited a good fit with the log-normal cumulative hazard function. This log-normal survival model can be used to help predict which patients will benefit from adjuvant chemoradiotherapy.

• Method comparison of automated matching software-assisted cone-beam CT and stereoscopic kilovoltage x-ray positional verification image-guided radiation therapy for head and neck cancer: a prospective analysis.

  Authors: Clifton D Fuller, Todd J Scarbrough, Jan-Jakob Sonke, Coen R N Rasch, Mehee Choi, Joe Y Ting, Samuel J Wang, Niko Papanikolaou, David I Rosenthal

  Physics in medicine and biology. 12/2009; 54(24):7401-15.

  We sought to characterize interchangeability and agreement between cone-beam computed tomography (CBCT) and digital stereoscopic kV x-ray (KVX) acquisition, two methods of isocenter positionalWe sought to characterize interchangeability and agreement between cone-beam computed tomography (CBCT) and digital stereoscopic kV x-ray (KVX) acquisition, two methods of isocenter positional verification currently used for IGRT of head and neck cancers (HNC). A cohort of 33 patients were near-simultaneously imaged by in-room KVX and CBCT. KVX and CBCT shifts were suggested using manufacturer software for the lateral (X), vertical (Y) and longitudinal (Z) dimensions. Intra-method repeatability, systematic and random error components were calculated for each imaging modality, as were recipe-based PTV expansion margins. Inter-method agreement in each axis was compared using limits of agreement (LOA) methodology, concordance analysis and orthogonal regression. 100 daily positional assessments were performed before daily therapy in 33 patients with head and neck cancer. Systematic error was greater for CBCT in all axes, with larger random error components in the Y- and Z-axis. Repeatability ranged from 9 to 14 mm for all axes, with CBCT showing greater repeatability in 2/3 axes. LOA showed paired shifts to agree 95% of the time within +/-11.3 mm in the X-axis, +/-9.4 mm in the Y-axis and +/-5.5 mm in the Z-axis. Concordance ranged from 'mediocre' to 'satisfactory'. Proportional bias was noted between paired X- and Z-axis measures, with a constant bias component in the Z-axis. Our data suggest non-negligible differences in software-derived CBCT and KVX image-guided directional shifts using formal method comparison statistics.A correction was made to the first line of page 7404 of this article on 26 November 2009. The corrected electronic version is identical to the print version.

• Relative lack of conditional survival improvement in young adults with cancer.

  Authors: Archie Bleyer, Mehee Choi, C David Fuller, Charles R Thomas, Samuel J Wang

  Seminars in oncology. 10/2009; 36(5):460-7.

  Cancer prognosis is usually reported in terms of survival from time of diagnosis. For patients surviving a period of time after diagnosis, conditional survival (CS) accounts for changing risk overCancer prognosis is usually reported in terms of survival from time of diagnosis. For patients surviving a period of time after diagnosis, conditional survival (CS) accounts for changing risk over time. This report provides information on how CS in cancer patients changes as a function of age at diagnosis. Using data from the US Surveillance, Epidemiology and End Results database, we examined survival for patients diagnosed between 1973 and 2002. The average annual percent change (AAPC) in CS during the first 5 years after diagnosis was evaluated for the 14 most common cancers occurring in young adults, defined as 15- to 39-year-olds, and how they compared with cancers that are more common in older and younger patients. For all cancers, young adult patients had less CS improvement over time than younger or older patients, and this difference was most pronounced in those aged 20 to 29 years (45% below the mean). Eleven of the 14 most common cancers in 15- to 39-year-olds either had a lower CS improvement after diagnosis than either younger or older patients, or than just the older patients. Young adults with leukemia had the greatest improvement in CS over time. In conclusion, young adults with cancer have not enjoyed the same improvement in CS over time compared with other age groups. Explanations for this deficit include the biologic nature of the type of cancers in young adults and less effective therapies for patients in the age group. Regardless of the reasons, the deficit is yet another challenge faced by young adult patients that merits further study.

• Multimodality therapy for locoregional extrahepatic cholangiocarcinoma : a population-based analysis.

  Authors: Clifton D Fuller, Samuel J Wang, Mehee Choi, Brian G Czito, John Cornell, Tania M Welzel, Katherine A McGlynn, Join Y Luh, Charles R Thomas

  Cancer. 08/2009;

  BACKGROUND:: Although surgical resection is the mainstay of treatment for extrahepatic cholangiocarcinoma, the majority of patients present with advanced disease. Due in part to numeric rarity, theBACKGROUND:: Although surgical resection is the mainstay of treatment for extrahepatic cholangiocarcinoma, the majority of patients present with advanced disease. Due in part to numeric rarity, the optimum role of radiotherapy (RT) for extrahepatic cholangiocarcinoma, as well as its relative benefit, is an area of debate. The specific aim of this series was to estimate survival for extrahepatic cholangiocarcinoma patients receiving surgery and adjuvant RT using a robust population-based data set. METHODS:: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) limited-use data set for selected extrahepatic cholangiocarcinoma cases. Lognormal multivariate survival analysis was implemented to estimate survival for patients for treatment cohorts based on extent of surgical intervention and RT. RESULTS:: Parametric estimated median survival for patients receiving total/radical resection + RT was 26 months; it was 25 months for total/radical resection alone, 25 months for subtotal/debulking resection + RT, 21 months for subtotal/debulking resection, 12 months for RT alone, and 9 months for those not receiving surgery or RT. Parametric multivariate analysis revealed age, American Joint Committee on Cancer Stage, grade, and surgical/radiation regimen as statistically significant covariates with survival. Surgery alone and adjuvant RT cohorts demonstrated evidence of improved survival compared with no treatment; comparatively, RT alone was associated with survival decrement. Early improvement in survival in adjuvant cohorts was not observed at later time points. CONCLUSIONS:: Survival estimates using SEER data suggest an early survival advantage for adjuvant RT for patients with locoregional extrahepatic cholangiocarcinoma. Although future prospective series are needed to confirm these observations, SEER data represent the largest domestic population-based extrahepatic cholangiocarcinoma cohort, and may provide useful baseline survival estimates for future studies. Cancer 2009. Published 2009 by the American Cancer Society.

• Increased vulnerability of the spinal cord to radiation or intrathecal chemotherapy during adolescence: A report from the Children's Oncology Group.

  Authors: Archie Bleyer, Mehee Choi, Samuel J Wang, Clifton D Fuller, R Beverly Raney

  Pediatric blood & cancer. 07/2009; 53(7):1205-1210.

  PURPOSE: To assess the rate of spinal cord toxicity in adolescents resulting from chemoradiotherapy of parameningeal sarcoma. METHODS AND MATERIALS: Of 152 patients with parameningeal sarcoma treatedPURPOSE: To assess the rate of spinal cord toxicity in adolescents resulting from chemoradiotherapy of parameningeal sarcoma. METHODS AND MATERIALS: Of 152 patients with parameningeal sarcoma treated per the Intergroup Rhabdomyosarcoma Study Group protocol from 1977 through 1989, eight developed paralyzing ascending myelitis after intrathecal chemotherapy with cytosine arabinoside, methotrexate, and hydrocortisone administered during and after radiation therapy to volumes that included part of the spinal cord. The eight cases include three not previously published. RESULTS: Of eight patients who developed CNS toxicity after intrathecal chemotherapy and radiotherapy for parameningeal rhabdomyosarcoma, all but one were between 13 and 18 years of age when treated. This severe toxicity occurred in one quarter of 28 adolescents treated with the regimen in comparison with one of 123 children 12 years of age or less (P < 0.0001), a rate that was as much as 30 times higher in the adolescents. Lengthening of the spinal cord during the pubertal growth spurt may account for the apparent increased vulnerability. CONCLUSIONS: Chemoradiotoxicity-associated spinal cord injury appears to be more likely to occur in adolescents than in younger or older ages. This observation appears to reverse a conventional wisdom in which the central nervous system is thought to become more resistant to the neurotoxic effects of chemoradiotherapy as it matures. Pediatr Blood Cancer 2009; 53:1205-1210. (c) 2009 Wiley-Liss, Inc.

• Image-guided intensity-modulated radiotherapy (IG-IMRT) for biliary adenocarcinomas: Initial clinical results.

  Authors: Clifton David Fuller, Nguyen Dinh Dang, Samuel J Wang, Prashant Desai, Mehee Choi, Charles R Thomas, Martin Fuss

  Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 04/2009;

  PURPOSE: Biliary tract lesions are comparatively rare neoplasms, with ambiguous indications for radiotherapy. The specific aim of this study was to report the clinical results of a single-institutionPURPOSE: Biliary tract lesions are comparatively rare neoplasms, with ambiguous indications for radiotherapy. The specific aim of this study was to report the clinical results of a single-institution biliary tract series treated with modern radiotherapeutic techniques, and detail results using both conventional and image-guided intensity-modulated radiation therapy (IG-IMRT). METHODS AND MATERIALS: From 2001 to 2005, 24 patients with primary adenocarcinoma of the biliary tract (gallbladder and extrahepatic bile ducts) were treated by IG-IMRT. To compare outcomes, data from a sequential series of 24 patients treated between 1995 and 2005 with conventional radiotherapy (CRT) techniques were collected as a comparator set. Demographic and treatment parameters were collected. Endpoints analyzed included treatment-related acute toxicity and survival. RESULTS: Median estimated survival for all patients completing treatment was 13.9 months. A statistically significant higher mean dose was given to patients receiving IG-IMRT compared to CRT, 59 vs. 48Gy. IG-IMRT and CRT cohorts had a median survival of 17.6 and 9.0 months, respectively. Surgical resection was associated with improved survival. Two patients (4%) experienced an RTOG acute toxicity score>2. The most commonly reported GI toxicities (RTOG Grade 2) were nausea or diarrhea requiring oral medication, experienced by 46% of patients. CONCLUSION: This series presents the first clinical outcomes of biliary tract cancers treated with IG-IMRT. In comparison to a cohort of patients treated by conventional radiation techniques, IG-IMRT was feasible for biliary tract tumors, warranting further investigation in prospective clinical trials.

• Effect of body mass index on shifts in ultrasound-based image-guided intensity-modulated radiation therapy for abdominal malignancies.

  Authors: Mehee Choi, Clifton D Fuller, Samuel J Wang, Ather Siddiqi, Adrian Wong, Charles R Thomas, Martin Fuss

  Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 10/2008;

  BACKGROUND AND PURPOSE: We investigated whether corrective shifts determined by daily ultrasound-based image-guidance correlate with body mass index (BMI) of patients treated with image-guidedBACKGROUND AND PURPOSE: We investigated whether corrective shifts determined by daily ultrasound-based image-guidance correlate with body mass index (BMI) of patients treated with image-guided intensity-modulated radiation therapy (IG-IMRT) for abdominal malignancies. The utility of daily image-guidance, particularly for patients with BMI>25.0, is examined. MATERIALS AND METHODS: Total 3162 ultrasound-directed shifts were performed in 86 patients. Direction and magnitude of shifts were correlated with pretreatment BMI. Bivariate statistical analysis and analysis of set-up correction data were performed using systematic and random error calculations. RESULTS: Total 2040 daily alignments were performed. Average 3D vector of set-up correction for all patients was 12.1mm/fraction. Directional and absolute shifts and 3D vector length were significantly different between BMI cohorts. 3D displacement averaged 4.9mm/fraction and 6.8mm/fraction for BMI25.0 and BMI>25.0, respectively. Systematic error in all axes and 3D vector was significantly greater for BMI>25.0. Differences in random error were not statistically significant. CONCLUSIONS: Set-up corrections derived from daily ultrasound-based IG-IMRT of abdominal tumors correlated with BMI. Daily image-guidance may improve precision of IMRT delivery with benefits assessed for the entire population, particularly patients with increased habitus. Requisite PTV margins suggested in the absence of daily image-guidance are significantly greater in patients with BMI>25.0.

• Prediction model for estimating the survival benefit of adjuvant radiotherapy for gallbladder cancer.

  Authors: Samuel J Wang, C David Fuller, Jong Sung Kim, Dean F Sittig, Charles R Thomas, Peter M Ravdin

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 06/2008; 26(13):2112-7.

  PURPOSE: The benefit of adjuvant radiotherapy (RT) for gallbladder cancer remains controversial because most published data are from small, single-institution studies. The purpose of this study wasPURPOSE: The benefit of adjuvant radiotherapy (RT) for gallbladder cancer remains controversial because most published data are from small, single-institution studies. The purpose of this study was to construct a survival prediction model to enable individualized predictions of the net survival benefit of adjuvant RT for gallbladder cancer patients based on specific tumor and patient characteristics. METHODS: A multivariate Cox proportional hazards model was constructed using data from 4,180 patients with resected gallbladder cancer diagnosed from 1988 to 2003 from the Surveillance, Epidemiology, and End Results database. Patient and tumor characteristics were included as covariates and assessed for association with overall survival (OS) with and without adjuvant RT. The model was internally validated for discrimination and calibration using bootstrap resampling. RESULTS: On multivariate regression analysis, the model showed that age, sex, papillary histology, stage, and adjuvant RT were significant predictors of OS. The survival prediction model demonstrated good calibration and discrimination, with a bootstrap-corrected concordance index of 0.71. The model predicts that adjuvant RT provides a survival benefit in node-positive or >or= T2 disease. A nomogram and a browser-based software tool were built from the model that can calculate individualized estimates of predicted net survival gain attributable to adjuvant RT, given specific input parameters. CONCLUSION: In the absence of large, prospective, randomized, clinical trial data, a regression model can be used to make individualized predictions of the expected survival improvement from the addition of adjuvant RT after gallbladder cancer resection.

• Conditional survival in ovarian cancer: results from the SEER dataset 1988-2001.

  Authors: Mehee Choi, Clifton D Fuller, Charles R Thomas, Samuel J Wang

  Gynecologic oncology. 06/2008; 109(2):203-9.

  OBJECTIVES: Survival statistics for patients with ovarian cancer are typically reported in terms of survival from time of diagnosis. For patients who have survived a period of time since diagnosis,OBJECTIVES: Survival statistics for patients with ovarian cancer are typically reported in terms of survival from time of diagnosis. For patients who have survived a period of time since diagnosis, however, conditional survival (CS) is a more clinically relevant measure, as it accounts for the changes in risk over time. The purpose of this study was to estimate CS for ovarian cancer patients through analysis of large-scale cancer registry data. METHODS: Ovarian cancer cases were extracted from the Surveillance, Epidemiology, and End Results (SEER 17) database from the National Cancer Institute (NCI) for patients diagnosed between 1988-2001. Five-year relative CS calculations were performed with stratification by age, race, stage, histology, and grade for patients who had already survived up to 5 years from diagnosis. RESULTS: The 5-year overall relative CS improved over time for up to 5 years after diagnosis for ovarian cancer patients. The largest gains in CS over time were seen for patients with advanced stage disease, poor grade, and serous and undifferentiated epithelioid histologies. For patients with stage IV disease, 5-year CS more than tripled over the first 5 years of surveillance (17%-56%). Among histological types, patients with undifferentiated epithelioid histology saw 5-year CS rise from 29% at diagnosis to 84% after 5 years. CONCLUSIONS: Prognosis improves over time for almost all groups of ovarian cancer patients. For ovarian cancer survivors, CS provides a more relevant measure of prognosis than conventional survival estimates that are made at the time of diagnosis.

• A cost-effectiveness analysis of adjuvant chemoradiotherapy for resected gastric cancer.

  Authors: Samuel J Wang, Clifton D Fuller, Mehee Choi, Charles R Thomas

  Gastrointestinal cancer research : GCR. 04/2008; 2(2):57-63.

  BACKGROUND: The Intergroup 0116 trial demonstrated that adding postoperative chemoradiotherapy for gastric cancer resulted in a significant overall survival improvement of 9 months. The purpose ofBACKGROUND: The Intergroup 0116 trial demonstrated that adding postoperative chemoradiotherapy for gastric cancer resulted in a significant overall survival improvement of 9 months. The purpose of this study was to perform a cost-effectiveness analysis of adjuvant chemoradiotherapy for resected gastric cancer. METHODS: An economic model was constructed to examine the costs and quality-adjusted survival benefit of adjuvant chemoradiotherapy for gastric cancer. Medicare reimbursement rates were used for chemotherapy and radiotherapy costs. Costs of managing toxicities were also included. Patient utilities were derived from published literature. The analysis was performed from the third-party payer perspective, with results reported in 2007 US dollars. A lifetime time horizon and 3% discount rate were used. One-way and Monte Carlo probabilistic sensitivity analyses were performed. RESULTS: For the base case, the incremental cost of adding adjuvant chemoradiotherapy was $20,100. The net gain in quality-adjusted life years (QALYs) was 0.53. The incremental cost-effectiveness ratio (ICER) was $38,400/QALY. The probabilistic sensitivity analysis predicted a 67% likelihood that the ICER would be less than $50,000/QALY. CONCLUSION: Our model suggests that the ICER of adjuvant chemoradiotherapy for resected gastric cancer compares favorably to other widely used cancer treatments.

• Survival prediction models for estimating the benefit of post-operative radiation therapy for gallbladder cancer and lung cancer.

  Authors: Jayashree Kalpathy-Cramer, William Hersh, Jong Sung Kim, Charles R Thomas, Samuel J Wang

  AMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium. 02/2008;

  The role of post-operative radiotherapy (PORT) is still controversial for some cancer sites. In the absence of large randomized controlled trials, survival prediction models can help estimate theThe role of post-operative radiotherapy (PORT) is still controversial for some cancer sites. In the absence of large randomized controlled trials, survival prediction models can help estimate the predicted benefit of PORT for specific settings. The purpose of this study was to compare the performance of two types of prediction models for estimating the benefit of PORT for 2 cancer sites. Using data from the Surveillance, Epidemiology, and End Results database, we constructed prediction models for gallbladder (GB) cancer and non-small cell lung cancer (NSMLC), using Cox proportional hazards and Random Survival Forests. We compared validation measures for discrimination and found that both the CPH and RSF models had comparable C-indices. For GB cancer, PORT was associated with improved survival for node positive patients, and for NSCLC, PORT was associated with a survival benefit for patients with N2 disease.

• Intensity-modulated Radiosurgery for patients with brain metastases: a mature outcomes analysis.

  Authors: Samuel J Wang, Mehee Choi, Clifton D Fuller, Bill J Salter, Martin Fuss

  Technology in cancer research & treatment. 07/2007; 6(3):161-8.

  The purpose of this study was to evaluate the outcomes of patients with brain metastases treated by tomotherapeutic Intensity-modulated Radiosurgery (IMRS). Using retrospective chart review, weThe purpose of this study was to evaluate the outcomes of patients with brain metastases treated by tomotherapeutic Intensity-modulated Radiosurgery (IMRS). Using retrospective chart review, we analyzed the outcomes of 78 patients (age 33-83 years, median 57 years) who underwent 111 sessions of IMRS (1 to 7 sessions per patient, median 1) for brain metastases (1 to 4 targets per IMRS session, median 1) treated between 2000 and 2005 using a serial tomotherapeutic intensity-modulated radiotherapy treatment (IMRT) planning and delivery system (Peacock, Nomos Corp., Cranberry Township, PA). Treatment planning was performed using an inverse treatment planning optimization algorithm that was optimized for IMRS. A median prescription dose of 15 Gy in combination with WBI, and median 20 Gy for IMRS alone was delivered using 2-4 couch angles over 4-24 rotational arcs. Overall survival was calculated using Kaplan-Meier analysis. To determine the effects of prognostic variables on survival, univariate and multivariate analyses using proportional hazards were performed to assess the effects of age, tumor size, the combination with whole brain irradiation, presence of multiple brain metastases, and presence of extracranial disease. The median overall survival was 6.5 months (95% CI, 5.5-7.9). One- and two-year survival rates were 24% and 10%. In multivariate analyses, age greater than 60 years was the only statistically significant variable that affected survival (hazard rate 1.29, p=0.049). We conclude that tomotherapeutic IMRS is safe and effective to treat patients with brain metastases.

• Conditional Survival in Rectal Cancer: A SEER Database Analysis.

  Authors: Samuel J Wang, Clifton D Fuller, Rachel Emery, Charles R Thomas

  Gastrointestinal cancer research : GCR. 06/2007; 1(3):84-9.

  PURPOSE: To provide an analysis of conditional survival (CS) in rectal cancer patients. Cancer survival is typically reported in terms of survival from time of diagnosis. CS can provide improvedPURPOSE: To provide an analysis of conditional survival (CS) in rectal cancer patients. Cancer survival is typically reported in terms of survival from time of diagnosis. CS can provide improved prognostic information for patients surviving a given period after diagnosis. METHODS: Data from 36,321 rectal cancer patients diagnosed between 1988 and 1998 were analyzed using the Surveillance, Epidemiology, and End Results (SEER 17) database. Observed 5-year CS rates according to disease stage, age, sex, and race were calculated using the life-table method. RESULTS: As survival from diagnosis increased from 0 to 5 years, the 5-year observed CS changed from 73% to 74% for stage I disease, 56% to 66% for stage II, 47% to 65% for stage III, and 6% to 48% for stage IV. Patients aged 65 years and over at diagnosis had lower CS than those under 65 years, both at diagnosis (45% vs. 61%) and at 5 years from diagnosis (59% vs. 81%). Men had slightly lower 5-year survival than women, both at diagnosis (50% vs. 53%) and after 5 years (68% vs. 71%). Black patients had slightly lower survival than white patients for nearly all time points and stages. CONCLUSION: For rectal cancer patients who survive a given period of time after diagnosis, the largest increases in CS are in patients with advanced stage disease and for those under 65 years of age. CS can provide more accurate prognostic information for rectal cancer patients who survive a given period after diagnosis.

• Ethnic disparities in conditional survival of patients with non-small cell lung cancer.

  Authors: Samuel J Wang, C David Fuller, Charles R Thomas

  Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 04/2007; 2(3):180-90.

  PURPOSE: Conditional survival (CS) is an accurate estimate of survival probability for patients who have already survived at least 1 year after diagnosis. The purpose of this study was to determinePURPOSE: Conditional survival (CS) is an accurate estimate of survival probability for patients who have already survived at least 1 year after diagnosis. The purpose of this study was to determine whether ethnicity plays a role in 5-year CS rates for patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results database, we analyzed 96,480 patients with NSCLC diagnosed between 1988 and 1995. Patients were divided into five ethnic groups: White (non-Hispanic), Hispanic, African American, Asian/Pacific Islander, and Native American/Alaskan. Using the life table method, we computed observed 5-year CS rates for patients who had already survived up to 5 years after diagnosis. Results were analyzed by stage, age, sex, and histology. RESULTS: In general, 5-year CS rates increase for all ethnicities as time from diagnosis increases, but African Americans continued to have lower CS rates compared with other ethnic groups, even up to 5 years from diagnosis. When analyzed by stage, Hispanics with stage IV disease showed the greatest improvement in CS rate, increasing to 73% at 5 years from diagnosis. Among patients older than 70 years, African Americans had the lowest CS at 5 years--only 28%, compared with 40% to 47% for other groups. When analyzed by histology, Hispanics with large cell carcinoma had the worst CS rate (35% at 5 years). CONCLUSION: For patients with NSCLC surviving a period of time after diagnosis, 5-year CS rates vary by ethnicity. CS can provide accurate prognostic information for patients with NSCLC who have already survived several years after diagnosis.

• Conditional survival in head and neck squamous cell carcinoma: results from the SEER dataset 1973-1998.

  Authors: Clifton D Fuller, Samuel J Wang, Charles R Thomas, Henry T Hoffman, Randal S Weber, David I Rosenthal

  Cancer. 04/2007; 109(7):1331-43.

  BACKGROUND: Survival statistics for patients with head and neck squamous cell carcinomas (HNSCC) are commonly calculated from the time of diagnosis. The less commonly employed conditional survivalBACKGROUND: Survival statistics for patients with head and neck squamous cell carcinomas (HNSCC) are commonly calculated from the time of diagnosis. The less commonly employed conditional survival (CS) analyzes survival for patients who have survived a period of time after diagnosis. Useful prognostic information for cancer survivors is provided by CS analysis. Estimated baseline CS parameters for HNSCC were sought using large-scale cancer registry data. METHODS: HNSCC cases identified from the Surveillance, Epidemiology, and End Results (SEER) Program were accessed to identify those diagnosed between 1973 and 1998. Five-year observed, relative, and cumulative CS calculations were performed, with secondary stratification by site, extent of disease, and age. RESULTS: The overall 5-year observed survival for all sites increased from 47.8% for 76,181 included patients from the time of diagnosis to 64.4% for those 43,985 patients alive at 3 years, and thereafter plateaus. The greatest increase in CS was for oropharyngeal cancers, which more than doubled over the first decade of surveillance (26.5%-60%). Distant disease showed a 10-year increase in CS (17.4%-60.4%), whereas localized disease CS was essentially static, ranging from 66.1% to 68.5%; for those over 65 at diagnosis it ranged from 39.9-52.9%, whereas patients <65 years at diagnosis ranged from 53.8-73.5%. CONCLUSIONS: Benchmark CS estimates for domestic HNSCC cohorts were developed from the SEER database. CS is a useful tool to assist clinicians in predicting the probability of demise from HNSCC for patients surviving 1 or more year after diagnosis.