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IMPORTANCE: In cancer clinical trials, symptomatic adverse events (AEs), such as nausea, are reported by investigators rather than by patients. There is increasing interest to collect symptomatic AE data via patient-reported outcome (PRO) questionnaires, but it is unclear whether it is feasible to implement this approach in multicenter trials. OBJECTIVE: To examine whether patients are willing and able to report their symptomatic AEs in multicenter trials. DESIGN, SETTING, AND PARTICIPANTS: A total of 361 consecutive patients enrolled in any 1 of 9 US multicenter cancer treatment trials were invited to self-report 13 common symptomatic AEs using a PRO adaptation of the National Cancer Institute���s Common Terminology Criteria for Adverse Events (CTCAE) via tablet computers at 5 successive clinic visits. Patient adherence was tracked with reasons for missed self-reports. Agreement with clinician AE reports was analyzed with weighted �� statistics. Patient and investigator perspectives were elicited by survey. The study was conducted from March 15, 2007, to August 11, 2011. Data analysis was performed from August 9, 2013, to March 21, 2014. RESULTS: Of the 361 patients invited to participate, 285 individuals enrolled, with a median age of 57 years (range, 24-88), 202 (74.3%) female, 241 (85.5%) white, 73 (26.8%) with a high school education or less, and 176 (64.7%) who reported regular internet use (denominators varied owing to missing data). Across all patients and trials, there were 1280 visits during which patients had an opportunity to self-report (ie, patients were alive and enrolled in a treatment trial at the time of the visit). Self-reports were completed at 1202 visits (93.9% overall adherence). Adherence was highest at baseline and declined over time (visit 1, 100%; visit 2, 96%; visit 3, 95%; visit 4, 91%; and visit 5, 85%). Reasons for missing PROs included institutional errors in 27 of 48 (56.3%) of the cases (eg, staff forgetting to bring computers to patients at visits), patients feeling ���too ill��� in 8 (16.7%), patient refusal in 8 (16.7%), and internet connectivity problems in 5 (10.4%). Patient-investigator CTCAE agreement was moderate or worse for most symptoms (most �� < 0.05), with investigators reporting fewer AEs than patients across symptoms. Most patients believed that the system was easy to use (234 [93.2%]) and useful (230 [93.1%]), and investigators thought that the patient-reported AEs were useful (133 [94.3%]) and accurate (119 [83.2%]). CONCLUSIONS AND RELEVANCE: Participants in multicenter cancer trials are willing and able to report their own symptomatic AEs at most clinic visits and report more AEs than investigators. This approach may improve the precision of AE reporting in cancer trials.

BACKGROUND To quantify and characterize duplicated tests performed during the staging of localized colon cancer in the Medicare population. METHODS We used the SEER-Medicare linked database to select patients diagnosed with localized colon cancer between the years 1996 and 2009. We considered a patient as adequately staged after having received a colonoscopy, an abdominal computed tomography (CT) scan, and a pelvic CT scan. Abdominal and pelvic CT scans performed between complete staging and first cancer-directed treatment, if not ordered due to an acute condition, were considered duplicates. We characterized the institutions providing the tests and evaluated the association with survival using a weighted pooled logistic regression adjusted by baseline and time-varying confounders. RESULTS Of 36,291 patients with a complete staging, 2680 (7.4%) had at least 1 duplicated test. Patients receiving a duplicate had a higher comorbidity score, were more symptomatic, and had more visits to the emergency department and clinical evaluations. They also were treated with surgery less frequently and had worse survival (hazard ratio 1.22, 95% confidence interval, 1.16-1.28). The type of institution involved in the staging (nonprofit/government centers, proprietary centers, free-standing facilities) was not associated with receiving duplicated tests. CONCLUSIONS We found a low frequency of duplicated abdominal or pelvic CT scans in the staging of colon cancer in the Medicare population.

Background:A substantial proportion of cancer-related mortality is attributable to recurrent, not de novo metastatic disease, yet we know relatively little about these patients. To fill this gap, investigators often use administrative codes for secondary malignant neoplasm or chemotherapy to identif

Appendiceal malignancies are rare and represent 1% of intestinal tumors in the United States. The role and efficacy of modern systemic therapy in advanced appendiceal adenocarcinoma has not been established. This study analyzed patients with recurrent or metastatic appendiceal adenocarcinoma in the database for Colorectal Cancer (CRC; 2005-2012). This database tracks longitudinal care for patients treated at 8 specialty centers across the Unites States. Study objectives were to describe and evaluate the efficacy of systemic therapy and investigate relationships with clinicopathologic features. Cox regression analysis was performed to identify predictors of progression-free survival (PFS) and overall survival (OS). Of 248 patients with advanced appendiceal carcinoma, 112 (45%) received systemic therapy for measurable disease and are the focus of this report. The most common chemotherapy regimens included FOLFOX with or without bevacizumab (n=39 and n=37, respectively), FOLFIRI (n=15), and single-agent fluoro-pyrimidine (n=10). Among 99 patients evaluable for best response, 39 experienced a response (response rate [RR], 39%) and 36 (36%) had stable disease. The median PFS was 1.2 years (95% CI, 1.0-1.8) and median OS was 2.1 years (95% CI, 1.6-2.3). Patients with non-mucinous histology or high-grade tumors and those who underwent nondebulking surgery had worse PFS and OS. Treatment of advanced appendiceal adenocarcinoma at NCCN Member Institutions commonly incorporates agents used for CRC. RR, PFS, and OS are comparable to those achieved in the treatment of metastatic CRC. Poor prognostic factors include nonmucinous histology or high-grade tumors and history of nondebulking surgery.

In a longitudinal clinical study to compare two groups, the primary end point is often the time to a specific event (eg, disease progression, death). The hazard ratio estimate is routinely used to empirically quantify the between-group difference under the assumption that the ratio of the two hazard functions is approximately constant over time. When this assumption is plausible, such a ratio estimate may capture the relative difference between two survival curves. However, the clinical meaning of such a ratio estimate is difficult, if not impossible, to interpret when the underlying proportional hazards assumption is violated (ie, the hazard ratio is not constant over time). Although this issue has been studied extensively and various alternatives to the hazard ratio estimator have been discussed in the statistical literature, such crucial information does not seem to have reached the broader community of health science researchers. In this article, we summarize several critical concerns regarding this conventional practice and discuss various well-known alternatives for quantifying the underlying differences between groups with respect to a time-to-event end point. The data from three recent cancer clinical trials, which reflect a variety of scenarios, are used throughout to illustrate our discussions. When there is not sufficient information about the profile of the between-group difference at the design stage of the study, we encourage practitioners to consider a prespecified, clinically meaningful, model-free measure for quantifying the difference and to use robust estimation procedures to draw primary inferences.

Purpose To identify and characterize potentially avoidable hospitalizations in patients with GI malignancies. Patients and Methods We compiled a retrospective series of sequential hospital admissions in patients with GI cancer. Patients were admitted to an inpatient medical oncology or palliative care service between December 2011 and July 2012. Practicing oncology clinicians used a consensus-driven medical record review process to categorize each hospitalization as “potentially avoidable” or “not avoidable.” Patient demographic and clinical data were abstracted, and quantitative and qualitative analyses were performed to identify patient characteristics and outcomes associated with potentially avoidable hospitalizations. Results We evaluated 201 hospitalizations in 154 unique patients. The median age was 62 years, and colorectal cancer was the most common diagnosis (32%). The majority of hospitalized patients had metastatic cancer (81%). In all, 53% of hospitalizations were attributable to cancer symptoms, and 28% were attributable to complications of cancer treatment. Medical oncologists identified 39 hospitalizations (19%) as potentially avoidable. Hospitalizations were more likely to be categorized as potentially avoidable for patients with the following characteristics: age ≥ 70 years (odds ratio [OR], 2.63; 95% CI, 1.15 to 6.02), receipt of an oncologist's advice to consider hospice (OR, 6.09; 95% CI, 2.54 to 14.58), or receipt of three or more lines of chemotherapy (OR, 2.68; 95% CI, 1.01 to 7.08). Ninety-day mortality was higher after avoidable hospitalizations compared with hospitalizations that were not avoidable (OR, 6.4; 95% CI, 1.8 to 22.3). Conclusion Potentially avoidable hospitalizations are common in patients with advanced GI cancer. The majority of potentially avoidable hospitalizations occurred in patients with advanced treatment-refractory cancers near the end of life.

Based on randomized data, neoadjuvant chemoradiotherapy has been incorporated into the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for stage II-III rectal cancer. Factors associated with nonadherence to evidence-based guidelines for neoadjuvant radiotherapy (RT) were examined at dedicated cancer centers. The prospective NCCN Oncology Outcomes Database for Colorectal Cancers was queried for patients with stage II-III rectal cancer who underwent a transabdominal surgical resection between September 2005 and June 2012. Multivariable logistic regression was used to identify factors associated with omission of RT. Among 1199 identified patients, 1119 (93%) received neoadjuvant RT, 51 (4%) did not receive RT, and 29 (2%) received adjuvant RT. Among 51 patients not receiving RT, only 19 (37%) were referred and evaluated by a radiation oncologist. On multivariable analysis, clinical factors associated with not receiving RT included a history of prior pelvic RT (adjusted odds ratio [aOR], 23.9; P=.0003), ECOG performance status of 2 or greater (aOR, 11.1; P=.01), tumor distance from the anal verge greater than 10 cm (aOR, 5.4; P=.009), age at diagnosis of 75 years or older (aOR, 4.43; P=.002), body mass index of 25 to 30 kg/m(2) and less than 25 kg/m(2) (aOR, 5.22 and 4.23, respectively; P=.03), and clinical stage II (aOR, 2.27; P=.02). No significant change was seen in RT use according to diagnosis year, nor was any correlation seen with distance to the nearest RT facility. Concordance with NCCN Guidelines for neoadjuvant RT is high among NCCN Member Institutions. After adjusting for clinical characteristics that increase the risk for RT toxicity, including history of pelvic RT and high comorbidity burden/low functional status, the authors found that non-obese patients of advanced age or those with more favorable clinical features were more likely to not receive RT.

Importance A rapid learning health care system for oncology will require scalable methods for extracting clinical end points from electronic health records (EHRs). Outside of clinical trials, end points such as cancer progression and response are not routinely encoded into structured data. Objective To determine whether deep natural language processing can extract relevant cancer outcomes from radiologic reports, a ubiquitous but unstructured EHR data source. Design, Setting, and Participants A retrospective cohort study evaluated 1112 patients who underwent tumor genotyping for a diagnosis of lung cancer and participated in the Dana-Farber Cancer Institute PROFILE study from June 26, 2013, to July 2, 2018. Exposures Patients were divided into curation and reserve sets. Human abstractors applied a structured framework to radiologic reports for the curation set to ascertain the presence of cancer and changes in cancer status over time (ie, worsening/progressing vs improving/responding). Deep learning models were then trained to capture these outcomes from report text and subsequently evaluated in a 10% held-out test subset of curation patients. Cox proportional hazards regression models compared human and machine curations of disease-free survival, progression-free survival, and time to improvement/response in the curation set, and measured associations between report classification and overall survival in the curation and reserve sets. Main Outcomes and Measures The primary outcome was area under the receiver operating characteristic curve (AUC) for deep learning models; secondary outcomes were time to improvement/response, disease-free survival, progression-free survival, and overall survival. Results A total of 2406 patients were included (mean [SD] age, 66.5 [10.8] years; 1428 female [59.7%]; 2170 [90.2%] white). Radiologic reports (n = 14 230) were manually reviewed for 1112 patients in the curation set. In the test subset (n = 109), deep learning models identified the presence of cancer, improvement/response, and worsening/progression with accurate discrimination (AUC >0.90). Machine and human curation yielded similar measurements of disease-free survival (hazard ratio [HR] for machine vs human curation, 1.18; 95% CI, 0.71-1.95); progression-free survival (HR, 1.11; 95% CI, 0.71-1.71); and time to improvement/response (HR, 1.03; 95% CI, 0.65-1.64). Among 15 000 additional reports for 1294 reserve set patients, algorithm-detected cancer worsening/progression was associated with decreased overall survival (HR for mortality, 4.04; 95% CI, 2.78-5.85), and improvement/response was associated with increased overall survival (HR, 0.41; 95% CI, 0.22-0.77). Conclusions and Relevance Deep natural language processing appears to speed curation of relevant cancer outcomes and facilitate rapid learning from EHR data.

The terms real-world data (RWD) and real-world evidence (RWE) have entered the medical lexicon to refer to data sources and analyses characterizing routine health care delivery. RWD and RWE are most often defined by what they are not: information from experiments such as randomized clinical trials.

BACKGROUND Pancreatic cancer is a major cause of morbidity and mortality in the Medicare population. Whether the health care burden of pancreatic cancer has changed over the last decade is unknown. METHODS The authors used Medicare data from 2000 to 2010 to identify beneficiaries aged ≥ 65 years who were hospitalized for the management of pancreatic cancer. Annual trends were estimated for the age-sex-race–adjusted initial hospitalization rate, the age-sex-race-comorbidity–adjusted 1-year mortality rate after initial hospitalization, age-sex-race-comorbidity–adjusted procedure rates, 1-year all-cause rehospitalizations after initial pancreatic cancer hospitalization, and mean inflation-adjusted Medicare payment for initial hospitalization. RESULTS A total of 130,728 patients had ≥ 1 hospitalizations for pancreatic cancer and were identified from 56,642,071 beneficiaries during the study period. The age-sex-race–adjusted rate of initial hospitalization for pancreatic cancer was 50 per 100,000 person-years in 2010, representing a 0.5% annual increase since 2000 (95% confidence interval [95% CI], 0.3%-0.7%). In the same period, the age-sex-race-comorbidity–adjusted 1-year mortality rate decreased by 4.4% (95% CI, 3.9%-4.9%), and the age-sex-race-comorbidity–adjusted surgical resection rate increased by 6.9% (95% CI, 6.4%-7.5%). The mean inflation-adjusted Medicare payment for the initial hospitalization decreased, from $14,118 in 2000 to $13,318 in 2010, and the number of 1-year all-cause rehospitalizations after the initial hospitalization increased from 0.75 per patient in 2000 to 0.82 per patient in 2009 (all P

Purpose The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing recent clinical practice guidelines that have been developed by other professional organizations. Methods The Cancer Care Ontario (CCO) Guideline on Follow-up Care, Surveillance Protocol, and Secondary Prevention Measures for Survivors of Colorectal Cancer was reviewed by ASCO for methodologic rigor and considered for endorsement. Results The ASCO Panel concurred with the CCO recommendations and recommended endorsement, with the addition of several qualifying statements. Conclusion Surveillance should be guided by presumed risk of recurrence and functional status of the patient (important within the first 2 to 4 years). Medical history, physical examination, and carcinoembryonic antigen testing should be performed every 3 to 6 months for 5 years. Patients at higher risk of recurrence should be considered for testing in the more frequent end of the range. A computed tomography scan (abdominal and chest) is recommended annually for 3 years, in most cases. Positron emission tomography scans should not be used for surveillance outside of a clinical trial. A surveillance colonoscopy should be performed 1 year after the initial surgery and then every 5 years, dictated by the findings of the previous one. If a colonoscopy was not preformed before diagnosis, it should be done after completion of adjuvant therapy (before 1 year). Secondary prevention (maintaining a healthy body weight and active lifestyle) is recommended. If a patient is not a candidate for surgery or systemic therapy because of severe comorbid conditions, surveillance tests should not be performed. A treatment plan from the specialist should have clear directions on appropriate follow-up by a nonspecialist.

The authors found that cost-related medication nonadherence was prevalent among patients with cancer who sought financial assistance.

BACKGROUND Treatment options for colorectal cancer (CRC) have improved substantially over the past 25 years. Measuring the impact of these improvements on survival outcomes is challenging, however, against the background of overall survival gains from advancements in the prevention, screening, and treatment of other conditions. Relative survival is a metric that accounts for these concurrent changes, allowing assessment of changes in CRC survival. We describe stage- and location-specific trends in relative survival after CRC diagnosis. METHODS We analyzed survival outcomes for 233965 people in the Surveillance Epidemiology and End Results (SEER) program who were diagnosed with CRC between January 1, 1975, and December 31, 2003. All models were adjusted for sex, race (black vs white), age at diagnosis, time since diagnosis, and diagnosis year. We estimated the proportional difference in survival for CRC patients compared with overall survival for age-, sex-, race-, and period-matched controls to account for concurrent changes in overall survival using two-sided Wald tests. RESULTS We found statistically significant reductions in excess hazard of mortality from CRC in 2003 relative to 1975, with excess hazard ratios ranging from 0.75 (stage IV colon cancer; P < .001) to 0.32 (stage I rectal cancer; P < .001), indicating improvements in relative survival for all stages and cancer locations. These improvements occurred in earlier years for patients diagnosed with stage I cancers, with smaller but continuing improvements for later-stage cancers. CONCLUSIONS Our results demonstrate a steady trend toward improved relative survival for CRC, indicating that treatment and surveillance improvements have had an impact at the population level.

The aim of this study was to determine the issues patients worry about when making decisions about cancer treatment. A total of 5,044 colorectal and lung cancer patients from the Cancer Care Outcomes Research and Surveillance Consortium reported their level of worry about (1) treatment side effects, (2) treatment costs, (3) time away from family, (4) time away from work, and (5) transportation to treatment sites. Using multivariable logistic regression, we evaluated the association of sociodemographic, clinical, and psychosocial variables with worry. Overall, 75 % of patients worried about side effects of treatments; 40 %, the cost of treatment; 50 %, time away from family; 52 %, time away from work; and 22 %, about transportation. In multivariable analyses, across all worry domains, older patients had lower odds of reporting worry (p values

BACKGROUND Rates of screening mammography have plateaued, and the number of mammography facilities has declined in the past decade. The objective of this study was to assess changes over time and geographic disparities in the availability of mammography services. METHODS Using information from the US Food and Drug Administration and the US Census, county-level mammography capacity was defined as the number of mammography machines per 10,000 women aged ≥ 40 years. Cross-sectional variation and longitudinal changes in capacity were examined in relation to county characteristics. RESULTS Between 2000 and 2010, the number of mammography facilities declined 10% from 9434 to 8469, the number of mammography machines declined 10% from 13,100 to 11,762, and the median county mammography capacity decreased nearly 20% from 1.77 to 1.42 machines per 10,000 women aged ≥ 40 years. In cross-sectional analysis, counties with greater percentages of uninsured residents, less educated residents, greater population density, and higher managed care penetration had lower mammography capacity. Conversely, counties with more hospital beds per 100,000 population had higher capacity. High initial mammography capacity, growth in both the percentage of the population aged ≥ 65 years and the percentage living in poverty, and increased managed care penetration were all associated with a decrease in mammography capacity between 2000 and 2010. Only the percentage of rural residents was associated with an increase in capacity. CONCLUSIONS Geographic variation in mammography capacity and declines in capacity over time are associated with demographic, socioeconomic, and health care market characteristics. Maldistribution of mammography resources may explain geographic disparities in breast cancer screening rates. Cancer 2013;119:3847–3853. © 2013 American Cancer Society.

Purpose Although radiation therapy (RT) can palliate symptoms and may prolong life, it is not curative for patients with metastatic lung cancer. We investigated patient expectations about the goals of RT for incurable lung cancers. Patients and Methods The Cancer Care Outcomes Research and Surveillance Consortium enrolled a population- and health system–based cohort of patients diagnosed with lung cancer from 2003 to 2005. We identified patients with stage wet IIIB or IV lung cancer who received RT and answered questions on their expectations about RT. We assessed patient expectations about the goals of RT and identified factors associated with inaccurate beliefs about cure. Results In all, 384 patients completed surveys on their expectations about RT. Seventy-eight percent of patients believed that RT was very or somewhat likely to help them live longer, and 67% believed that RT was very or somewhat likely to help them with problems related to their cancer. However, 64% did not understand that RT was not at all likely to cure them. Older patients and nonwhites were more likely to have inaccurate beliefs, and patients whose surveys were completed by surrogates were less likely to have inaccurate beliefs. Ninety-two percent of patients with inaccurate beliefs about cure from RT also had inaccurate beliefs about chemotherapy. Conclusion Although patients receiving RT for incurable lung cancer believe it will help them, most do not understand that it is not at all likely to cure their disease. This indicates a need to improve communication regarding the goals and limitations of palliative RT.

The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a library of question items that enables patient reporting of adverse events (AEs) in clinical trials. This study contributes content validity evidence of the PRO-CTCAE by incorporating cancer patient input of the relevance and comprehensiveness of the item library.Cognitive interviews were conducted among patients undergoing chemotherapy or radiation therapy at multiple sites to evaluate comprehension, memory retrieval, judgment, and response mapping related to AE terms (e.g., nausea), attribute terms (regarding frequency, severity, or interference), response options, and recall period. Three interview rounds were conducted with ≥20 patients completing each item per round. Items were modified and retested if ≥3 patients exhibited cognitive difficulties or if experienced by ≤25% patients.One hundred and twenty-seven patients participated (35% ≤high school, 28% non-white, and 59% female). Most AE terms (63/80) generated no cognitive difficulties. The remaining 17 were modified without further difficulties by Round 3. Terms were comprehended regardless of education level. Attribute terms and response options required no modifications. Patient adherence to recall period (7 days) was improved when the reference period was incorporated.This study provides evidence confirming comprehension of the US English language versions of items in the PRO-CTCAE library for measuring symptomatic AEs from the patient perspective within the context of cancer treatment. Several minor changes were made to the items to improve item clarity, comprehension, and ease of response judgment. This study helps to establish the content validity of PRO-CTCAE items for patient reporting of AEs during cancer treatment.

Purpose Medicare patients with advanced cancer have low rates of hospice use. We sought to evaluate hospice use among patients in Medicaid, which insures younger and indigent patients, relative to those in Medicare. Patients and Methods Using linked patient-level data from California (CA) and New York (NY) state cancer registries, state Medicaid programs, NY Medicare, and CA Surveillance, Epidemiology, and End Results–Medicare data, we identified 4,797 CA Medicaid patients and 4,001 NY Medicaid patients ages 21 to 64 years, as well as 27,416 CA Medicare patients and 16,496 NY Medicare patients ages ≥ 65 years who were diagnosed with stage IV lung cancer between 2002 and 2006. We evaluated hospice use, timing of enrollment, and location of death (inpatient hospice; long-term care facility or skilled nursing facility; acute care facility; home with hospice; or home without hospice). We used multiple logistic regressions to evaluate clinical and sociodemographic factors associated with hospice use. Results Although 53% (CA) and 44% (NY) of Medicare patients ages ≥ 65 years used hospice, fewer than one third of Medicaid-insured patients ages 21 to 64 years enrolled in hospice after a diagnosis of stage IV lung cancer (CA, 32%; NY, 24%). A minority of Medicaid patient deaths (CA, 19%; NY, 14%) occurred at home with hospice. Most Medicaid patient deaths were either in acute-care facilities (CA, 28%; NY, 36%) or at home without hospice (CA, 39%; NY, 41%). Patient race/ethnicity was not associated with hospice use among Medicaid patients. Conclusion Given low rates of hospice use among Medicaid enrollees and considerable evidence of suffering at the end of life, opportunities to improve palliative care delivery should be prioritized.

Purpose Patient-reported outcomes are increasingly used in routine outpatient cancer care to guide clinical decisions and enhance communication. Prior evidence suggests good patient compliance with reporting at scheduled clinic visits, but there is limited evidence about compliance with long-term longitudinal reporting between visits. Patients and Methods Patients receiving chemotherapy for lung, gynecologic, genitourinary, or breast cancer at a tertiary cancer center, with access to a home computer and prior e-mail experience, were asked to self-report seven symptomatic toxicities via the Web between visits. E-mail reminders were sent to participants weekly; patient-reported high-grade toxicities triggered e-mail alerts to nurses; printed reports were provided to oncologists at visits. A priori threshold criteria were set to determine if this data collection approach merited further development based on monthly (≥ 75% participants reporting at least once per month on average) and weekly compliance rates (60% at least once per week). Results Between September 2006 and November 2010, 286 patients were enrolled (64% were women; 88% were white; median age, 58 years). Mean follow-up was 34 weeks (range, 2 to 214). On average, monthly compliance was 83%, and weekly compliance was 62%, without attrition until the month before death. Greater compliance was associated with older age and higher education but not with performance status. Compliance was greatest during the initial 12 weeks. Symptomatic illness and technical problems were rarely barriers to compliance. Conclusion Monthly compliance with home Web reporting was high, but weekly compliance was lower, warranting strategies to enhance compliance in routine care settings.

Management of locally advanced rectal cancer is complex because curative treatment routinely involves administration of surgery, chemotherapy, and radiation. Optimal treatment delivery sequencing and timing are challenging, and moreover, there is considerable heterogeneity in risk based on rectal tumor location, extent, and nodal involvement. The goal in rectal cancer treatment is to optimize disease-free and overall survival while minimizing the risk of local recurrence and toxicity from both radiation and systemic therapy. Currently, the standard approach to management of locally advanced (T3 or T2) rectal cancer involves careful staging with a pelvic MRI and proctoscopic evaluation by a surgeon experienced in total mesorectal excision. MRI can help to distinguish between patients in low-, intermediate-, and high-risk categories. Low-risk tumors have no evidence of either extramural spread or nodal involvement and proximal location in the rectum. For such patients, R0 resection is almost always possible and immediate surgery often is reasonable. In the minority of cases where unanticipated lymph node involvement is detected at surgical pathology, postoperative radiation can be administered. Patients who opt for up-front rectal surgery need to understand that although there is a chance that radiation can be avoided, if it is necessary, it is less well tolerated when administered postoperatively. Initial surgical treatment should be reserved for low-risk patients for whom imaging indicates and multidisciplinary team members feel is able to undergo an R0 resection with low chance for regional spread of disease. For patients with high-risk disease based on distal tumor location requiring an APR, threatened radial margins, or T4 tumors, preoperative chemoradiation is essential. Indeed, this approach increases the likelihood of complete surgical resection with negative margins. For some high-risk patients, for example those with T4 or bulky nodal disease, preoperative systemic therapy followed by preoperative chemoradiation and then surgery may be optimal. The feasibility of this approach is well established based on nonrandomized trials, but it has not been evaluated in a randomized study. Preoperative administration of systemic therapy can achieve clinical downstaging, optimize rates of sphincter preservation, and establish tumor responsiveness, which may be valuable for incorporation into future treatment decisions. For patients with intermediate-risk T3 rectal cancers, for example, a cT3N1 tumor 7 cm from the anal verge with two to three regional lymph nodes in the 7-mm range, we encourage participation in the PROSPECT randomized trial, which is now open and accruing at numerous centers in North America, and shortly in Europe and South America as well. This study will determine in the era of optimal imaging, surgical technique, and better systemic chemotherapy, whether pelvic radiation remains an essential component of curative treatment. The PROSPECT study uses chemoradiation selectively rather than automatically and customizes subsequent treatment based on response to neoadjuvant FOLFOX. Clinical trials with interventions that tailor treatment to more precisely defined clinical subgroups based on both initial features and tumor responsiveness are expected to become the norm. Although this trend is likely to make clinical trial design more complex, customized treatment strategies are likely to achieve the optimal balance between under- and overtreatment and will address the heterogeneity of both tumor biology and disease presentation. For now, treatment for a patient with clinical T3N1 tumor in the mid rectum consists of the following components: ·Neoadjvuant chemoradiation with either 5-fluorouracil or capecitabine as sensitizing therapy. ·Low anterior resection with total mesorectal excision. Typically a temporary diverting ostomy is required. ·Postoperative administration of adjuvant systemic therapy, 8 cycles of FOLFOX is appropriate, although oxaliplatin should be omitted for early signs of peripheral neuropathy or on the basis of age/comorbidity. Although this is the current care standard, there is concern that such extensive treatment is not necessary for all patients to prevent local recurrence and to optimize cure. To determine if therapy can be streamlined, participation in PROSPECT or other clinical trials asking compelling clinical questions is a priority.

For low-lying rectal cancers, proximal diversion can reduce anastomotic leak after sphincter-preserving surgery; however, evidence suggests that such temporary diversions are often not reversed. We aimed to evaluate nonreversal and delayed stoma reversal in elderly patients undergoing low anterior resection (LAR).SEER-Medicare-linked analysis from 1991-2007.A total of 1179 primary stage I-III rectal cancer patients over age 66 who underwent LAR with synchronous diverting stoma.(1) Stoma creation and reversal rates; (2) time to reversal; (3) characteristics associated with reversal and shorter time to reversal.Within 18 mo of LAR, 51% of patients (603/1179) underwent stoma reversal. Stoma reversal was associated with age80 y (P0.0001), male sex (P = 0.018), fewer comorbidities (P = 0.017), higher income (quartile 4 versus 1; P = 0.002), early tumor stage (1 versus 3; P0.001), neoadjuvant radiation (P0.0001), rectal tumor location (versus rectosigmoid; P = 0.001), more recent diagnosis (P = 0.021), and shorter length of stay on LAR admission (P = 0.021). Median time to reversal was 126 d (interquartile range: 79-249). Longer time to reversal was associated with older age (P = 0.031), presence of comorbidities (P = 0.014), more advanced tumor stage (P = 0.007), positive lymph nodes (P = 0.009), receipt of adjuvant radiation therapy (P = 0.008), more recent diagnosis (P = 0.004), and longer length of stay on LAR admission (P0.0001).Half of elderly rectal cancer patients who undergo LAR with temporary stoma have not undergone stoma reversal by 18 mo. Identifiable risk factors predict both nonreversal and longer time to reversal. These results help inform preoperative discussions and promote realistic expectations for elderly rectal cancer patients.

BACKGROUND Randomized trials report equivalent efficacy among various combinations of platinum-based regimens in advanced non–small cell lung cancer (NSCLC). Their relative effectiveness and comparability based on squamous versus nonsquamous histology is uncertain. METHODS The authors used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data to identify first-line chemotherapy agents administered to Medicare beneficiaries with stage IIIB or IV NSCLC diagnosed from 2000 to 2007. Overall survival was compared between patients who received the 3 most common regimens: carboplatin-paclitaxel, carboplatin-gemcitabine, and carboplatin-docetaxel. Stratified analyses distinguished between the outcomes of patients with squamous versus nonsquamous cell histology. Multivariable Cox proportional hazards models and propensity score analyses facilitated adjustment for imbalance in measurable patient characteristics. RESULTS Of the 15,318 patients who received first-line chemotherapy, 43.1% received carboplatin-paclitaxel, 14.3% received carboplatin-gemcitabine, 8.5% received carboplatin-docetaxel, and 34.1% received other regimens. The median survival was 8.0 months (interquartile range [IQR], 3.5-17.4 months) for carboplatin-paclitaxel, 7.3 months (IQR, 3.4-15.2 months) for carboplatin-gemcitabine, and 7.5 months (IQR, 3.2-16.0 months) for carboplatin-docetaxel. Both multivariable and propensity score-adjusted Cox models demonstrated a slight inferiority associated with carboplatin-gemcitabine or carboplatin-docetaxel versus carboplatin-paclitaxel, with a hazard ratio of 1.10 (95% confidence interval, 1.04-1.15) and 1.09 (95% confidence interval, 1.02-1.16), respectively, in propensity score-stratified models. Among the subgroup of 2063 patients with squamous carcinoma, propensity score-stratified analyses had a higher risk of death (hazard ratio, 1.20; 95% confidence interval, 1.07-1.35) associated with carboplatin-gemcitabine versus carboplatin-paclitaxel. CONCLUSIONS Carboplatin-paclitaxel was associated with slightly better survival compared with carboplatin-gemcitabine or carboplatin-docetaxel within the Medicare population with advanced NSCLC, and this was most pronounced for patients who had squamous cell histology. Cancer 2013;119:2048–2060. © 2013 American Cancer Society.

Purpose Randomized data suggest that single-fraction or short-course palliative radiation therapy (RT) is sufficient in the majority of patients with metastatic cancer. We investigated population-based patterns in the use of palliative RT among patients with metastatic non–small-cell lung cancer (NSCLC). Patients and Methods From patients diagnosed with lung cancer from 2003 to 2005 at a participating geographic or organizational site and who consented to the Cancer Care Outcomes Research and Surveillance Consortium study, we identified patients with metastatic NSCLC who had complete medical records abstractions. Patient characteristics and clinical factors associated with receipt of palliative RT and RT intensity (total dose and number of treatments) were evaluated with multivariable regression. Results Of 1,574 patients with metastatic NSCLC, 780 (50%) received at least one course of RT, and 21% and 12% received RT to the chest and bone, respectively. Use of palliative RT was associated with younger age at diagnosis and receipt of chemotherapy and surgery to metastatic sites. Among patients receiving palliative bone RT, only 6% received single-fraction treatment. Among patients receiving palliative chest RT, 42% received more than 20 fractions. Patients treated in integrated networks were more likely to receive lower doses and fewer fractions to the bone and chest. Conclusion When palliative RT is used in patients with metastatic NSCLC, a substantial proportion of patients receive a greater number of treatments and higher doses than supported by current evidence, suggesting an opportunity to improve care delivery.

Purpose Practice guidelines recommend that patients who receive neoadjuvant chemotherapy and radiation for locally advanced rectal cancer complete postoperative adjuvant systemic chemotherapy, irrespective of tumor downstaging. Patients and Methods The National Comprehensive Cancer Network (NCCN) Colorectal Cancer Database tracks longitudinal care for patients treated at eight specialty cancer centers across the United States and was used to evaluate how frequently patients with rectal cancer who were treated with neoadjuvant chemotherapy also received postoperative systemic chemotherapy. Patient and tumor characteristics were examined in a multivariable logistic regression model. Results Between September 2005 and December 2010, 2,073 patients with stage II/III rectal cancer were enrolled in the database. Of these, 1,193 patients receiving neoadjuvant chemoradiotherapy were in the analysis, including 203 patients not receiving any adjuvant chemotherapy. For those seen by a medical oncologist, the most frequent reason chemotherapy was not recommended was comorbid illness (25 of 50, 50%); the most frequent reason chemotherapy was not received even though it was recommended or discussed was patient refusal (54 of 74, 73%). After controlling for NCCN Cancer Center and clinical TNM stage in a multivariable logistic model, factors significantly associated with not receiving adjuvant chemotherapy were age, Eastern Cooperative Oncology Group performance status ≥ 1, on Medicaid or indigent compared with private insurance, complete pathologic response, presence of re-operation/wound infection, and no closure of ileostomy/colostomy. Conclusion Even at specialty cancer centers, a sizeable minority of patients with rectal cancer treated with curative-intent neoadjuvant chemoradiotherapy do not complete postoperative chemotherapy. Strategies to facilitate the ability to complete this third and final component of curative intent treatment are necessary.

Background. The Cancer-Specific Geriatric Assessment (CSGA) is a primarily self-administered paper survey of validated measures. Methods. We developed and tested the feasibility of a computer-based CSGA in patients ≥70 years of age who were receiving treatment for gastrointestinal malignancies at the Dana-Farber Cancer Institute. From December 2009 to June 2011, patients were invited to complete the CSGA at baseline (start of new treatment) and follow-up (at the first of 4 months later or within 4 weeks of completing treatment). Feasibility endpoints were proportion of eligible patients consented, proportion completing CSGA at baseline and follow-up, time to complete CSGA, and proportion of physicians reporting CSGA results that led to a change in clinical decision-making. Results. Of the 49 eligible patients, 38 consented (76% were treatment naive). Median age was 77 years (range: 70–89 years), and 48% were diagnosed with colorectal cancer. Mean physician-rated Karnofsky Performance Status was 87.5 at baseline (SD 8.4) and 83.5 at follow-up (SD 8). At baseline, 92% used a touchscreen computer; 97% completed the CSGA (51% independently). At follow-up, all patients used a touchscreen computer; 71% completed the CSGA (41% independently). Mean time to completion was 23 minutes at baseline (SD 8.4) and 20 minutes at follow-up (SD 5.1). The CSGA added information to clinical assessment for 75% at baseline (n = 27) and 65% at follow-up (n = 17), but it did not alter immediate clinical decision-making. Conclusion. The computer-based CSGA feasibility endpoints were met, although approximately half of patients required assistance. The CSGA added information to clinical assessment but did not affect clinical decision-making, possibly due to limited alternate treatment options in this subset of patients.

Patients often anticipate cure from palliative chemotherapy. Better resources are needed to convey its risks and benefits. We describe the stakeholder-driven development and acceptability testing of a prototype video and companion booklet supporting informed consent (IC) for a common palliative chemotherapy regimen.Our multidisciplinary team (researchers, advocates, clinicians) employed a multistep process of content development, production, critical evaluation, and iterative revisions. Patient/clinician stakeholders were engaged throughout using stakeholder advisory panels, featuring their voices within the intervention, conducting surveys and qualitative interviews. A national panel of 57 patient advocates, and 25 oncologists from nine US practices critiqued the intervention and rated its clarity, accuracy, balance, tone, and utility. Participants also reported satisfaction with existing chemotherapy IC materials.Few oncologists (5/25, 20%) or advocates (10/22, 45%) were satisfied with existing IC materials. In contrast, most rated our intervention highly, with 89-96% agreeing it would be useful and promote informed decisions. Patient voices were considered a key strength. Every oncologist indicated they would use the intervention regularly.Our intervention was acceptable to advocates and oncologists. A randomized trial is evaluating its impact on the chemotherapy IC process.Stakeholder-driven methods can be valuable for developing patient educational interventions.

Importance Large regional variation exists in the use of radiotherapy after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). Although patients who do not receive initial radiotherapy for DCIS are candidates for subsequent BCS if they experience a second breast event, many undergo mastectomy instead. Objective To examine whether regional practice patterns of radiotherapy for DCIS affect the use of mastectomy in these patients. Design, Setting, and Participants A retrospective analysis of population-based databases (Surveillance, Epidemiology, and End Results [SEER] and SEER-Medicare). Data were obtained for 2679 women in SEER with a diagnosis of DCIS between 1990 and 2011 and for 757 women in SEER-Medicare with a DCIS diagnosis between 1991 and 2009 who had not undergone radiotherapy for DCIS and experienced a subsequent breast cancer or DCIS diagnosis. Exposures Treatment intensity for primary DCIS (high, medium, low), as defined by separating health service areas (HSAs) into 3 clusters based on radiotherapy use. Main Outcomes and Measures Mastectomy vs BCS at a second breast event defined as DCIS recurrence or new invasive cancer. Results The median (SD) ages of the participants was 64 (13) years for the 2679 SEER population and 79 (6) years for the SEER-Medicare cohort. Residence in an HSA characterized by greater radiotherapy use for DCIS increased the likelihood of receiving mastectomy vs BCS at a subsequent breast event, even among women who had not previously received radiotherapy for DCIS. Adjusted odds ratios for receiving mastectomy were 1.43 (95% CI, 1.10-1.85) and 1.90 (95% CI, 1.27-2.84) in SEER and SEER-Medicare databases, respectively, among women residing in an HSA with the greatest radiotherapy use vs the least, corresponding to an adjusted increase from 40.8% to 49.6%, and from 38.6% to 54.5%. Conclusions and Relevance Areas with more radiotherapy use for DCIS had increased use of mastectomy at the time of a second breast event even among patients eligible for breast conservation. This association suggests that physician-related factors are affecting the likelihood of breast preservation.

Background : Propensity score (PS) analysis is increasingly being used in observational studies, especially in some cancer studies where random assignment is not feasible. This systematic review evaluates the use and reporting quality of PS analysis in oncology studies. Methods : We searched PubMed to identify the use of PS methods in cancer studies (CS) and cancer surgical studies (CSS) in major medical, cancer, and surgical journals over time and critically evaluated 33 CS published in top medical and cancer journals in 2014 and 2015 and 306 CSS published up to November 26, 2015, without earlier date limits. The quality of reporting in PS analysis was evaluated. It was also compared over time and among journals with differing impact factors. All statistical tests were two-sided. Results More than 50% of the publications with PS analysis from the past decade occurred within the past two years. Of the studies critically evaluated, a considerable proportion did not clearly provide the variables used to estimate PS (CS 12.1%, CSS 8.8%), incorrectly included non baseline variables (CS 3.4%, CSS 9.3%), neglected the comparison of baseline characteristics (CS 21.9%, CSS 15.6%), or did not report the matching algorithm utilized (CS 19.0%, CSS 36.1%). In CSS, the reporting of the matching algorithm improved in 2014 and 2015 ( P = .04), and the reporting of variables used to estimate PS was better in top surgery journals ( P = .008). However, there were no statistically significant differences for the inclusion of non baseline variables and reporting of comparability of baseline characteristics. Conclusions The use of PS in cancer studies has dramatically increased recently, but there is substantial room for improvement in the quality of reporting even in top journals. Herein we have proposed reporting guidelines for PS analyses that are broadly applicable to different areas of medical research that will allow better evaluation and comparison across studies applying this approach.

There is strong concern about the costs associated with adding tumor-treating fields (TTF) therapy to standard first-line treatment for glioblastoma (GBM). Hence, we aimed to determine the cost-effectiveness of TTF therapy for the treatment of newly diagnosed patients with GBM.We developed a 3-health-state Markov model. The perspective was that of the French Health Insurance, and the horizon was lifetime. We calculated the transition probabilities from the survival parameters reported in the EF-14 trial. The main outcome measure was incremental effectiveness expressed as life-years gained (LYG). Input costs were derived from the literature. We calculated the incremental cost-effectiveness ratio (ICER) expressed as cost/LYG. We used 1-way deterministic and probabilistic sensitivity analysis to evaluate the model uncertainty.In the base-case analysis, adding TTF therapy to standard of care resulted in increases of life expectancy of 4.08 months (0.34 LYG) and €185 476 per patient. The ICER was €549 909/LYG. The discounted ICER was €596 411/LYG. Parameters with the most influence on ICER were the cost of TTF therapy, followed equally by overall survival and progression-free survival in both arms. The probabilistic sensitivity analysis showed a 95% confidence interval of the ICER of €447 017/LYG to €745 805/LYG with 0% chance to be cost-effective at a threshold of €100 000/LYG.The ICER of TTF therapy at first-line treatment is far beyond conventional thresholds due to the prohibitive announced cost of the device. Strong price regulation by health authorities could make this technology more affordable and consequently accessible to patients.

Medicaid beneficiaries with cancer are less likely to receive timely and high-quality care. This study examined whether differences in state-level Medicaid policies affect delays in time to surgery (TTS) among women diagnosed with breast cancer. Using 2006-2008 Medicaid data, we identified women aged 18-64 enrolled in Medicaid diagnosed with breast cancer. Analyses examined associations of state-specific Medicaid surgery reimbursements, Medicaid eligibility recertification period (annually vs. shorter) and required patient copayment on time from breast cancer diagnosis to receipt of breast surgery. Patients receiving neoadjuvant therapy were excluded. Separate multivariable regression analyses controlling for patient demographic characteristics and clustering by state were performed for breast conserving surgery (BCS), inpatient mastectomy, and outpatient mastectomy. The study included 7542 Medicaid beneficiaries with breast cancer: 3272 received BCS, 2156 outpatient mastectomy, and 2115 inpatient mastectomy. Higher Medicaid reimbursements for BCS were associated with decreased time from diagnosis to surgery. A 12-month (vs.

If cancer is the emperor of all maladies, then pancreatic adenocarcinoma is the ruthless dictator of all cancers. In 2016, there will be an estimated 53 070 new diagnoses and 41 780 deaths from pancreatic cancer in the United States.1 Pancreatic cancer has recently surpassed breast cancer (40 890 deaths) as a cause of death in the United States and ranks below only lung cancer and colorectal cancer in the number of cancer-related deaths annually.1 Globally, more than 340 000 cases are diagnosed each year and the incidence rates and mortality rates are nearly identical.2 Pancreas cancer mortality rates have not substantially declined over the past decade, and the incidence is increasing in low- and middle-resource countries.

It is unknown whether the addition of temozolomide (TMZ) to radiotherapy (RT) is associated with improved overall survival (OS) among older glioblastoma patients. We performed a retrospective cohort SEER-Medicare analysis of 1652 patients aged ≥65 years with glioblastoma who received ≥10 fractions of RT from 2005 to 2009, or from 1995 to 1999 before TMZ was available. Three cohorts were assembled based on diagnosis year and treatment initiated within 60 days of diagnosis: (1) 2005-2009 and TMZ/RT, (2) 2005-2009 and RT only, or (3) 1995-1999 and RT only. Associations with OS were estimated using Cox proportional hazards models and propensity score analyses; OS was calculated starting 60 days after diagnosis. Pre-specified sensitivity analyses were performed among patients who received long-course RT (≥27 fractions). Median survival estimates were 7.4 (IQR, 3.3-14.7) months for TMZ/RT, 5.9 (IQR, 2.6-12.1) months for RT alone in 2005-2009, and 5.6 (IQR, 2.7-9.6) months for RT alone in 1995-1999. OS at 2 years was 10.1 % for TMZ/RT, 7.1 % for RT in 2005-2009, and 4.7 % for RT in 1995-1999. Adjusted models suggested decreased mortality risk for TMZ/RT compared to RT in 2005-2009 (AHR, 0.86; 95 % CI, 0.76-0.98) and RT in 1995-1999 (AHR, 0.71; 95 % CI, 0.57-0.90). Among patients from 2005 to 2009 who received long-course RT, however, the addition of TMZ did not significantly improve survival (AHR, 0.91; 95 % CI, 0.80-1.04). In summary, among a large cohort of older glioblastoma patients treated in a real-world setting, the addition of TMZ to RT was associated with a small survival gain.

Background PRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. Methods Participants (n = 112; median age 56.5; 24 % high school or less) receiving treatment for cancer at seven US sites completed 28 PRO-CTCAE items (scoring range 0–4) by three modes (order randomized) at a single study visit. Subjects completed one page (approx. 15 items) of the EORTC QLQ-C30 between each mode as a distractor. Item scores by mode were compared using intraclass correlation coefficients (ICC); differences in scores within the 3-mode crossover design were evaluated with mixed-effects models. Difficulties with each mode experienced by participants were also assessed. Results 103 (92 %) completed questionnaires by all three modes. The median ICC comparing tablet vs IVRS was 0.78 (range 0.55–0.90); tablet vs paper: 0.81 (0.62–0.96); IVRS vs paper: 0.78 (0.60–0.91); 89 % of ICCs were ≥0.70. Item-level mean differences by mode were small (medians [ranges] for tablet vs. IVRS = −0.04 [−0.16–0.22]; tablet vs paper = −0.02 [−0.11–0.14]; IVRS vs paper = 0.02 [−0.07–0.19]), and 57/81 (70 %) items had bootstrapped 95 % CI around the effect sizes within +/−0.20. The median time to complete the questionnaire by tablet was 3.4 min; IVRS: 5.8; paper: 4.0. The proportion of participants by mode who reported “no problems” responding to the questionnaire was 86 % tablet, 72 % IVRS, and 98 % paper. Conclusions Mode equivalence of items was moderate to high, and comparable to test-retest reliability (median ICC = 0.80). Each mode was acceptable to a majority of respondents. Although the study was powered to detect moderate or larger discrepancies between modes, the observed ICCs and very small mean differences between modes provide evidence to support study designs that are responsive to patient or investigator preference for mode of administration, and justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration. Trial registration NCT Clinicaltrials.gov identifier: NCT02158637

Objective Assess validity of the retrospective Dartmouth hospital referral region (HRR) end-of-life spending measures by comparing with health care expenditures from diagnosis to death for prospectively identified advanced lung cancer patients. Data/Setting/Design We calculated health care spending from diagnosis (2003–2005) to death or through 2011 for 885 patients aged ≥65 years with advanced lung cancer using Medicare claims. We assessed the association between Dartmouth HRR-level spending in the last 2 years of life and patient-level spending using linear regression with random HRR effects, adjusting for patient characteristics. Findings For each $1 increase in the Dartmouth metric, spending for our cohort increased by $0.74 (p

Hormone therapy is the mainstay of adjuvant treatment for hormone receptor positive (HR-positive) nonmetastatic breast cancer. We evaluated adjuvant hormone therapy (AHT) initiation among Medicaid-insured women aged 21-64 years with stage I-III HR-positive breast cancer. We used multivariable logistic regression to identify independent predictors of AHT initiation. Within 1 year of diagnosis, 68% (1049/1538) initiated AHT; by 18 months, 80% (1168/1461) initiated AHT. In multivariable analysis, women less likely to initiate AHT had more comorbidity (≥ 2 vs none: adjusted odds ratio (AOR) = 0.55; 95% CI = 0.32 to 0.97), more advanced disease (stage III vs I: AOR = 0.27; 95% CI = 0.18 to 0.39), and no radiation after breast conserving surgery (AOR = 0.15; 95% CI = 0.10 to 0.22). Race, age, and history of mental health disorders were not independently associated with initiation of AHT. Among initiators of AHT, 58% (604/1049) were adherent to treatment for the year after initiation. Despite comprehensive prescription coverage, only 39% (604/1538) received optimal AHT including prompt initiation and adherence for the year after treatment. Partnerships between Medicaid programs and cancer registries may help identify at-risk women and facilitate the implementation of quality improvement strategies.

BACKGROUND: In clinical trials, combined 5-fluorouracil (5FU) plus oxaliplatin improves the survival of patients who have resected, stage III colon cancer with manageable toxicity. However, the tolerability of this in the general population of patients with colon cancer is uncertain. METHODS: Adverse outcomes were compared in patients with stage III colon cancer who received either 5FU or 5FU/oxaliplatin within 120 days of undergoing resection versus a control group of patients with stage II colon cancer who did not receive chemotherapy in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and in data from the New York State Cancer Registry linked to Medicare and Medicaid. Hospitalizations, emergency room (ER) visits, and outpatient adverse events (AEs) were measured in claims from 30 days to 9 months after patients underwent resection. Multiple logistic regression was used to calculate adjusted odds ratios of events by treatment. Propensity score matching was used to minimize selection bias. RESULTS: Adverse outcomes were more frequent for chemotherapy recipients. AE rates were higher in patients who received 5FU/oxaliplatin (81%) compared with patients who received 5FU alone (72%), in the SEER-Medicare data. The effect of oxaliplatin on AEs was greater in older patients: The odds ratio was 2.10 (95% confidence interval, 1.53-2.87) for patients aged ≥75 years versus 1.75 (95% confidence interval, 1.39-2.21) for patients aged

Purpose Cancer staging determines extent of disease, facilitating prognostication and treatment decision making. The American Joint Committee on Cancer (AJCC) TNM classification system is the most commonly used staging algorithm for colon cancer, categorizing patients on the basis of only these three variables (tumor, node, and metastasis). The purpose of this study was to extend the seventh edition of the AJCC staging system for colon cancer to incorporate additional information available from tumor registries, thereby improving prognostic accuracy. Methods Records from 128,853 patients with primary colon cancer reported to the Surveillance, Epidemiology and End Results Program from 1994 to 2005 were used to construct and validate three survival models for patients with primary curative-intent surgery. Independent training/test data sets were used to develop and test alternative models. The seventh edition TNM staging system was compared with models supplementing TNM staging with additional demographic and tumor variables available from the registry by calculating a concordance index, performing calibration, and identifying the area under receiver operating characteristic (ROC) curves. Results Inclusion of additional registry covariates improved prognostic estimates. The concordance index rose from 0.60 (95% CI, 0.59 to 0.61) for the AJCC model, with T- and N-stage variables, to 0.68 (95% CI, 0.67 to 0.68) for the model including tumor grade, number of collected metastatic lymph nodes, age, and sex. ROC curves for the extended model had higher sensitivity, at all values of specificity, than the TNM system; calibration curves indicated no deviation from the reference line. Conclusion Prognostic models incorporating readily available data elements outperform the current AJCC system. These models can assist in personalizing treatment and follow-up for patients with colon cancer.

To determine the ability of dynamic contrast enhanced (DCE-MRI) to predict pathological complete response (pCR) after preoperative chemotherapy for rectal cancer.In a prospective clinical trial, 23/34 enrolled patients underwent pre- and post-treatment DCE-MRI performed at 1.5T. Gadolinium 0.1 mmol/kg was injected at a rate of 2 mL/s. Using a two-compartmental model of vascular space and extravascular extracellular space, K(trans), k(ep), v(e), AUC90, and AUC180 were calculated. Surgical specimens were the gold standard. Baseline, post-treatment and changes in these quantities were compared with clinico-pathological outcomes. For quantitative variable comparison, Spearman's Rank correlation was used. For categorical variable comparison, the Kruskal-Wallis test was used. P ≤ 0.05 was considered significant.Percentage of histological tumour response ranged from 10 to 100%. Six patients showed pCR. Post chemotherapy K(trans) (mean 0.5 min(-1) vs. 0.2 min(-1), P = 0.04) differed significantly between non-pCR and pCR outcomes, respectively and also correlated with percent tumour response and pathological size. Post-treatment residual abnormal soft tissue noted in some cases of pCR prevented an MR impression of complete response based on morphology alone.After neoadjuvant chemotherapy in rectal cancer, MR perfusional characteristics have been identified that can aid in the distinction between incomplete response and pCR.Dynamic contrast enhanced (DCE) MRI provides perfusion characteristics of tumours. These objective quantitative measures may be more helpful than subjective imaging alone Some parameters differed markedly between completely responding and incompletely responding rectal cancers. Thus DCE-MRI can potentially offer treatment-altering imaging biomarkers.

Purpose The extent to which new techniques for the delivery of radiotherapy for head and neck squamous cell carcinoma (HNSCC) have diffused into clinical practice is unclear, including the use of 3-dimensional conformal RT (3D-RT) and intensity-modulated radiation therapy (IMRT). Methods and Materials Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we identified 2,495 Medicare patients with Stage I–IVB HNSCC diagnosed at age 65 years or older between 2000 and 2005 and treated with either definitive (80%) or adjuvant (20%) radiotherapy. Our primary aim was to analyze the trends and predictors of IMRT use over this time, and the secondary aim was a similar description of the trends and predictors of conformal radiotherapy (CRT) use, defined as treatment with either 3D-RT or IMRT. Results Three hundred sixty-four (15%) patients were treated with IMRT, and 1,190 patients (48%) were treated with 3D-RT. Claims for IMRT and CRT rose from 0% to 33% and 39% to 86%, respectively, between 2000 and 2005. On multivariable analysis, IMRT use was associated with SEER region (West 18%; Northeast 11%; South 12%; Midwest 13%), advanced stage (advanced, 21%; early, 9%), non-larynx site (non-larynx, 23%; larynx, 7%), higher median census tract income (highest vs. lowest quartile, 18% vs. 10%), treatment year (2003–2005, 31%; 2000–2002, 6%), use of chemotherapy (26% with; 9% without), and higher radiation oncologist treatment volume (highest vs. lowest tertile, 23% vs. 8%). With CRT as the outcome, only SEER region, treatment year, use of chemotherapy, and increasing radiation oncologist HNSCC volume were significant on multivariable analysis. Conclusions The use of IMRT and CRT by Medicare beneficiaries with HNSCC rose significantly between 2000 and 2005 and was associated with both clinical and non-clinical factors, with treatment era and radiation oncologist HNSCC treatment volume serving as the strongest predictors of IMRT use.

To assess the impact of mammography capacity on appointment wait times.We surveyed by telephone all mammography facilities federally certified in 2008 in California, Connecticut, Georgia, Iowa, New Mexico, and New York using a simulated patient format. County-level mammography capacity, defined as the number of mammography machines per 10,000 women aged 40 and older, was estimated from FDA facility certification records and US Census data.1,614 (86%) of 1,882 mammography facilities completed the survey. Time until next available screening mammogram appointment was1 week at 55% of facilities, 1-4 weeks at 34% of facilities, and1 month at 11% of facilities. Facilities in counties with lower capacity had longer wait times, and a one-unit increase in county capacity was associated with 21% lower odds of a facility reporting a wait time1 month (p0.01). There was no association between wait time and the availability of evening or weekend appointments or digital mammography.Lower mammography capacity is associated with longer wait times for screening mammograms.Enhancement of mammography resources in areas with limited capacity may reduce wait times for screening mammogram appointments, thereby increasing access to services and rates of breast cancer screening.

Purpose Adverse symptom event reporting is vital as part of clinical trials and drug labeling to ensure patient safety and inform risk-benefit decision making. The purpose of this study was to assess the reliability of adverse event reporting of different clinicians for the same patient for the same visit. Methods A retrospective reliability analysis was completed for a sample of 393 cancer patients (42.8% men; age 26-91, M = 62.39) from lung (n = 134), prostate (n = 113), and Ob/Gyn (n = 146) clinics. These patients were each seen by two clinicians who independently rated seven Common Terminology Criteria for Adverse Events (CTCAE) symptoms. Twenty-three percent of patients were enrolled in therapeutic clinical trials. Results The average time between rater evaluations was 68 min. Intraclass correlation coefficients were moderate for constipation (0.50), diarrhea (0.58), dyspnea (0.69), fatigue (0.50), nausea (0.52), neuropathy (0.71), and vomiting (0.46). These values demonstrated stability over follow-up visits. Two-point differences, which would likely affect treatment decisions, were most frequently seen among symptomatic patients for constipation (18%), vomiting (15%), and nausea (8%). Conclusion Agreement between different clinicians when reporting adverse symptom events is moderate at best. Modification of approaches to adverse symptom reporting, such as patient self-reporting, should be considered.

Purpose Previous studies have examined predictors for initiation of adjuvant chemotherapy in stages II and III colon cancer. However, little is known regarding the use of specific chemotherapy regimens or treatment duration. Patients and Methods We studied treatment records for 2,560 patients with stage II or III colon cancer who received adjuvant chemotherapy between January 2004 and April 2010 at US cancer care facilities participating in a nationwide, commercially available chemotherapy order entry system that captures patient demographics, stage, and details of chemotherapy treatment. Multivariate analyses of prospectively recorded patient and provider characteristics identified predictors of specific therapeutic approaches. Results The addition of oxaliplatin to fluoropyrimidine-based adjuvant therapy increased during the study period (P trend < .001), and this combination represented 78% and 90% of adjuvant chemotherapy in stage II or III disease, respectively, by 2007. Older patients, those with diminished performance status, and those treated in a private practice setting were significantly less likely to receive oxaliplatin. Thirty percent of patients discontinued adjuvant therapy after less than 3 months. Older age, oxaliplatin-containing therapy, and receipt of treatment from a physician with a low volume of patients were each independently associated with premature discontinuation. Six percent of patients received bevacizumab as part of their adjuvant regimen. Conclusion After 2004, oxaliplatin and fluoropyrimidine-based therapy rapidly became the predominant adjuvant treatment for both stage II and stage III colon cancer in this large US cohort. Both increasing patient age and lower volume of an oncologist's practice were associated with early termination of adjuvant therapy.

Background. Because poverty is difficult to measure, its association with outcomes for serious illnesses such as hematologic cancers remains largely uncharacterized. Using Medicaid enrollment as a proxy for poverty, we aimed to assess potential disparities in survival after a diagnosis of acute myeloid leukemia (AML) or Hodgkin's lymphoma (HL) in a nonelderly population. Methods. We used records from the New York (NY) and California (CA) state cancer registries linked to Medicaid enrollment records for these states to identify Medicaid enrolled and nonenrolled patients aged 21–64 years with incident diagnoses of AML or HL in 2002–2006. We compared overall survival for the two groups using Kaplan–Meier curves and Cox proportional hazards analyses adjusted for sociodemographic and clinical factors. Results. For HL, the adjusted risk for death for Medicaid enrolled compared with nonenrolled patients was 1.98 (95% confidence interval [CI], 1.47–2.68) in NY and 1.89 (95% CI, 1.43–2.49) in CA. In contrast, for AML, Medicaid enrollment had no effect on survival (adjusted hazard ratio, 1.00; 95% CI, 0.84–1.19 in NY and hazard ratio, 1.02; 95% CI, 0.89–1.16 in CA). These results persisted despite adjusting for race/ethnicity and other factors. Conclusions. Poverty does not affect survival for AML patients but does appear to be associated with survival for HL patients, who, in contrast to AML patients, require complex outpatient treatment. Challenges for the poor in adhering to treatment regimens for HL could explain this disparity and merit further study.

The National Cancer Institute (NCI) is developing a patient-reported version of its Common Terminology Criteria for Adverse Events, called the "PRO-CTCAE." The PRO-CTCAE consists of a library of patient-reported items which can be administered in clinical trials to directly capture the patient experience of adverse events during cancer treatment, as well as a software platform for administering these items via computer or telephone. In order to better understand the impressions of stakeholders involved in cancer clinical research about the potential value of the PRO-CTCAE approach to capturing adverse event information in clinical research, as well as their perspectives about barriers and strategies for implementing the PRO-CTCAE in NCI-sponsored cancer trials, a survey was conducted. A survey including structured and open-ended questions was developed to elicit perceptions about the use of patient-reported outcomes (PROs) for adverse event reporting, and to explore logistical considerations for implementing the PRO-CTCAE in cancer trials. The survey was distributed electronically and by paper to a convenience sample of leadership and committee members in the NCI's cooperative group network, including principal investigators, clinical investigators, research nurses, data managers, patient advocates, and representatives of the NCI and Food and Drug Administration. Between October, 2008 through February, 2009, 727 surveys were collected. Most respondents (93%) agreed that patient reporting of adverse symptoms would be useful for improving understanding of the patient experience with treatment in cancer trials, and 88%, 80%, and 76%, respectively, endorsed that administration of PRO-CTCAE items in clinical trials would improve the completeness, accuracy, and efficiency of symptom data collection. More than three fourths believed that patient reports would be useful for informing treatment dose modifications and towards FDA regulatory evaluation of drugs. Eighty-eight percent felt that patients in clinical trials would be willing to self-report adverse symptoms at clinic visits via computer, and 68% felt patients would self-report weekly from home via the internet or an automated telephone system. Lack of computers and limited space and personnel were seen as potential barriers to in-clinic self-reporting, but these were judged to be surmountable with adequate funding. The PRO-CTCAE items and software are viewed by a majority of survey respondents as a means to improve adverse event data quality and comprehensiveness, enhance clinical decision-making, and foster patient-clinician communication. Research is ongoing to assess the measurement properties and feasibility of implementing this measure in cancer clinical trials.

This paper describes a linkage between the New York State Cancer Registry (NYSCR) and the New York State (NYS) Medicaid program, both housed within the New York State Department of Health (NYSDOH). Medicaid, the state-based health program for individuals and families with low incomes and resources in the United States, insures approximately one-sixth of New York adults aged 18–64 and one-fifth of elderly over 65, most of whom are dually enrolled in Medicare and Medicaid. Deficiencies in cancer care are known to disproportionately affect the poor as well as racial and ethnic minorities who are overrepresented in Medicaid (Agency for Healthcare Research and Quality 2005; Institute of Medicine 2005; Landon et al. 2007;). The Surveillance, Epidemiology and End Results (SEER)–Medicare linkage is the prototype for our effort (Warren et al. 2002; National Cancer Institute, Division of Cancer Control and Population Sciences, Health Services and Economics Branch 2009;). This linkage has enabled the development of a resource containing information on over 3 million elderly persons with cancer, which has yielded a large number of influential publications describing the patterns and outcomes of cancer care in the United States (Warren et al. 2002; Hershman et al. 2007; Wong et al. 2007; Gooden et al. 2008; Morris et al. 2008; White et al. 2008;). The SEER program collects demographic and diagnostic information for persons diagnosed with cancer, historically representing about 14 percent of the U.S. population and more recently expanded to cover 26 percent. SEER data provide detailed characterizations of cancer diagnosis, tumor stage, and initial treatment but do not track care longitudinally other than vital status. Linkage with Medicare claims for enrollees in fee-for-service plans enables characterization of covered health services longitudinally. A comparable match to Medicaid records has seldom been attempted owing to technical and procedural obstacles (Bradley, Given, and Roberts 2001; Bradley et al. 2007;). These obstacles include the fact that each state's Medicaid program is distinct, that Medicaid enrollment can be discontinuous, and that managed care penetration might be high and thus limit the utility of the claims for ascertaining care. The few attempts to construct registry—Medicaid linkages at the state level include those in Michigan (Bradley, Given, and Roberts 2001, 2002, 2003), California (Perkins et al. 2001; Chan et al. 2006;), Ohio (Koroukian et al. 2006a, 2006b), Washington (Ramsey et al. 2008), and Louisiana (Whitaker et al. 2009). The NYSCR–Medicaid linkage has two primary objectives. The first, discussed in this paper, is to create a deidentified analytic dataset for use in ongoing research projects with extramural partners. We will be using this dataset, for example, to compare community-dwelling cancer patients by Medicaid status, stage distribution, and receipt of quality care to identify whether racial and ethnic disparities exist within the Medicaid program. Findings will be related to timing and duration of enrollment, as those who enrolled in Medicaid in response to a cancer diagnosis might have quite different diagnostic or demographic characteristics than long-term enrollees. The second objective is to assess the degree to which Medicaid claims data add value to the cancer treatment information already collected by the NYSCR, with an emphasis on the treatment of breast and colorectal cancer. The collection of detailed treatment information is a relatively new undertaking for most U.S. cancer registries that are not part of the SEER program; treatment data for New York are considered complete only for cases diagnosed beginning in 2003. Even for this “complete” data, the amount of missing information is typically more than double that seen in SEER. For example, 3.2 percent of colorectal cancer cases diagnosed in NYS between 2004 and 2006 have unknown surgery information, compared with 1.3 percent in SEER. In addition, there is potentially useful information in claims records that cancer registries do not collect at all, such as screening utilization, prescription medications, and nursing home services. Claims data also provide a means for independently verifying that information being collected by central registries is correct. In this paper, we detail the data linkage process and the resulting analytic dataset. We report the percentage of cancer cases matching to the Medicaid enrollment files by cancer site, stage, age, marital status, race/ethnicity, and geography, and show how these differ in important ways from the cancer population generally. We then discuss ways in which the linkage enhanced the quality of registry data, some of which were unanticipated. Finally, we discuss file size issues as the single largest technical hurdle encountered.

292 Background: Routine collection of patient reported outcomes (PROs) reduces hospitalizations and improves quality of life. In the absence of clear implementation guidelines and research guiding deployment, PROs may not have the desired impact on outcomes in routine oncology practice. We share lessons learned from PRO deployment at Dana-Farber Cancer Institute. Methods: We developed a symptom/toxicity assessment tool based on the PRO-CTCAE to capture 15 symptomatic adverse events with a 1-week recall: fatigue/ decreased appetite/insomnia/ shortness of breath/numbness and tingling/concentration, general pain/anxiety/sadness, rash, nausea/vomiting/fever, constipation, and diarrhea. Responses from eligible English-literate patients scheduled for a gastrointestinal cancer center or adult palliative care visit between January 18 to March 22, 2018 were transmitted directly from clinic tablet to the EMR. To evaluate the deployment, we sought qualitative feedback from clinic staff and three multidisciplinary working groups comprised of patients, nurses, pharmacists, operations leaders, quality/safety experts, and health services researchers to identify technical and workflow gaps in PRO Content, Implementation, and Analytics. Results: We noted a 38% response rate of the N = 4440 PROs assigned to N = 4440 scheduled visits for N = 2055 unique patients (36% were completed, 2% started but not completed); 62% were not started. Workflow enhancement requests include an updated summary view, a clinical documentation tool, a scoring algorithm to highlight severe responses, and a quality metric dashboard to evaluate the deployment. Ongoing analyses are studying the proportion of moderate-severe symptomatic adverse events reported and their association with provider action (i.e., supportive care referral, chemotherapy treatment plan modification, or unplanned ED/hospitalization in the subsequent 30 days). Conclusions: Refinement of the PRO deployment strategy is needed to guide implementation efforts and demonstrate meaningful impact in routine oncology practice.

Key Points Question Does the risk of hospitalization among elderly patients receiving chemotherapy for metastatic, nonsquamous, non–small cell lung cancer vary by chemotherapy regimen? Findings In a cohort study of 2182 propensity-matched Medicare beneficiaries with non–small cell lung cancer, the 30-day hospitalization risk was 5% lower for patients receiving carboplatin with pemetrexed (21%) than for those receiving carboplatin with paclitaxel (26%), a statistically significant difference. Meaning When multiple standard-of-care chemotherapy regimens are available in a specific treatment setting, measures of regimen-specific hospitalization risk may be relevant for treatment selection., Importance Chemotherapy is a mainstay treatment of metastatic non–small cell lung cancer. However, little is known about the comparative risk of hospitalization associated with commonly used chemotherapy regimens. Objective To evaluate the real-world association of specific lung cancer chemotherapy regimens with measures of acute hospital care (primary objective) and survival (secondary objective). Design, Setting, and Participants Retrospective, propensity-matched, cohort study using the Surveillance, Epidemiology, and End Results–Medicare linked data for cancer diagnoses between 2008 and 2013, with follow-up through 2014. Patients were Medicare beneficiaries 66 years of age or older receiving initial chemotherapy for treatment of stage IV, nonsquamous, non–small cell lung cancer. Analyses were performed between September 2017 and April 2018. Exposures Receipt of chemotherapy with carboplatin-pemetrexed or carboplatin-paclitaxel, with or without concurrent bevacizumab. Main Outcomes and Measures The primary outcome was risk of hospitalization within 30 days of chemotherapy initiation. Secondary measures included cumulative 90-day hospitalizations, 90-day mean hospital-free survival time, and overall survival. Results Of the 3310 eligible patients, 1823 received carboplatin-pemetrexed, and 1487 received carboplatin-paclitaxel. The median age at diagnosis was 73 years (interquartile range, 69-77 years), 1784 patients (53.9%) were men, and 2909 patients (87.9%) were non-Hispanic white. In total, 2182 patients were included in the propensity-matched analysis. The 30-day hospitalization risk was 20.7% (95% CI, 18.3%-23.1%) among patients receiving carboplatin-pemetrexed vs 26.0% (95% CI, 23.4%-28.6%) among patients receiving carboplatin-paclitaxel (5.3% difference; P = .003). The 90-day cumulative hospitalizations did not differ significantly between the 2 treatment groups; however, the 90-day mean hospital-free survival time was improved for patients receiving carboplatin-pemetrexed (68.4 days [95% CI, 66.5-70.4 days] vs 63.6 days [95% CI, 61.6-65.7 days]; P = .001). The median survival time was 9.0 months (95% CI, 8.4-9.5 months) with carboplatin-pemetrexed therapy vs 7.6 months (95% CI, 7.0-8.4 months) with carboplatin-paclitaxel therapy (P = .005). Stratified analyses showed no association of bevacizumab use with hospitalization risk or survival when combined with either chemotherapy regimen. Conclusions and Relevance The findings from this study suggest that patients receiving carboplatin-pemetrexed compared with those receiving carboplatin-paclitaxel have a lower 30-day hospitalization risk, a greater 90-day hospital-free survival, and improved overall survival. Information about hospitalization risk may provide valuable context for evaluating real-world cancer treatment outcomes., This cohort study analyzes Medicare claims linked with Surveillance, Epidemiology, and End Results (SEER) program data to assess hospitalization risk and survival among US patients receiving carboplatin-paclitaxel or carboplatin-pemetrexed for treatment of metastatic, nonsquamous, non–small cell lung cancer.

Colorectal cancer is the third most common cancer and the third leading cause of cancer death in the United States. Approximately 15% of colorectal cancers are characterized by deficient DNA mismatch repair (MMR), leading to microsatellite instability (MSI) and mutations in critical genes involved in carcinogenesis, such as transforming growth factortype II receptor and BAX. It has long been recognized that MSI-high (MSI-H) tumors are pathologically distinct from colorectal tumors that arise from the traditional chromosomal instability pathway, with a predominantly proximal location in the right colon, poorer differentiation, mucinous histology, and peritumoral lymphocytic infiltration. Recent studies revealed that this pathologically unique subset of colorectal cancers also harbored significant differences in clinical behavior. Indeed, the seminal article by Ribic et al published in the New England Journal of Medicine in 2003 showed that among patients with stage II and III colon cancer pooled from five large, randomized clinical trials of adjuvant chemotherapy, 17% had MSI-H tumors. Patients with MSI-H tumors had a modestly better prognosis than those with microsatellite-stable (MSS) or MSIlow (MSI-L) cancers, yet also did not seem to benefit from adjuvant fluorouracil (FU) -based chemotherapy. This resistance to FU is presumably due to incorporation of FU metabolites into DNA rather than inhibition of its effective target, thymidylate synthase. In this issue of Journal of Clinical Oncology, Sargent et al have confirmed and extended these previous findings. They analyzed an additional 457 patients with stage II and III colon cancer from four of the five trials included in the Ribic study, as well as from another randomized trial of FU and leucovorin (LV) by the Gruppo Italiano di Valutazione Interventi in Oncologia (GIVIO). They found that deficient MMR status was associated with significantly improved 5-year disease-free survival (DFS) on univariate analysis (P .03), though not on multivariate analysis, in patients who were randomly assigned to surgery alone. Interestingly, in the subset of patients randomly assigned to adjuvant chemotherapy, MMR status did not seem to influence DFS, although the hazard ratios (HRs) do suggest a slight advantage for those with MMR deficiency. The authors then evaluated the impact of adjuvant chemotherapy according to MMR status, and, consistent with multiple large randomized trials, found a significant benefit for FU-based treatment on DFS, but only in patients with proficient MMR (multivariate HR 0.67; 95% CI, 0.48 to 0.93; P .02). Among stage II and III colon cancers characterized by MMR deficiency, absolutely no benefit was seen with adjuvant FU-based chemotherapy (multivariate HR for DFS 1.39; 95% CI, 0.46 to 4.15; P .56). For added power, the authors pooled data from these 457 patients with that of the 570 patients in Ribic et al’s original analysis and came to similar conclusions; namely, deficient MMR status was prognostic for a better outcome only in patients treated with surgery alone, and was not associated with a DFS or overall survival benefit from adjuvant FU-based chemotherapy (P interaction .04). The larger number of patients in this pooled analysis allowed an interesting exploration of treatment effect by MMR status and stage of cancer. Among stage III patients with intact MMR, adjuvant chemotherapy led to a statistically significant improvement in DFS (HR 0.64; 95% CI, 0.48 to 0.84; P .001), but no differences in outcome were seen in MMR-deficient stage III cancer (HR 1.01; 95% CI, 0.41 to 2.51; P .98). Among patients with stage II colon cancer, those with proficient MMR status had a nonsignificant 16% reduction in the relative risk of recurrence or death, whereas there was a trend toward worse outcome in tumors with MMR deficiency (P .09). These differential findings between deficient and intact MMR status, and between stage II and stage III colon cancer, are important and may have clinical implications for treatment. A strength of this pooled analysis by Sargent et al is its inclusion of large, international clinical trials that randomly assigned patients with colon cancer to both an adjuvant FU treatment arm and a nontreatment arm. This study design is critical for determining whether MSI-H is prognostic, predictive, or both. A prognostic biomarker is one that is associated with clinical outcome in the absence of therapy or with administration of standard therapy, and often reflects the natural history of the cancer. A control group from a randomized clinical trial is the ideal population to test the prognostic abilities of a marker, and indeed, Sargent et al demonstrate that deficient MMR status is a favorable prognostic marker for stage II and III colon cancer patients treated with surgery alone. In contrast, a predictive marker is one that is associated with differential response to a specific treatment (in this case, adjuvant FU), based on the status of the biomarker, and is statistically represented as a significant interaction between the biomarker and treatment response. With their large, pooled database, the authors were able to show that response to adjuvant FU-based chemotherapy is statistically dependent on MMR status. Thus, with these current data that tumors with MMR deficiency are both prognostic for better outcome and predictive for lack of benefit from adjuvant FU-based treatment, should such therapy be JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L S VOLUME 28 NUMBER 20 JULY 1