The experience of financial toxicity among advanced melanoma patients treated with immunotherapy.

Purpose To measure financial toxicity and explore its association with quality of life (QOL) in an emerging population of survivors: advanced melanoma patients treated with immunotherapy. Design Cross-sectional survey and medical record review. Sample 106 survivors (39% response). Median time since start of immunotherapy was 36.4 months (range: 14.2-133.9). Methods The Comprehensive Score for Financial Toxicity measured financial toxicity, and the EORTC-QLQ30 assessed QOL and functioning across five domains. Data were collected online, by phone, or in clinic. Findings: Younger patients (<65 years) reported higher financial toxicity (p < .001) than older patients. Controlling for age, financial toxicity was correlated with QOL (p < .001), financial difficulties (p < .001), and EORTC-QLQ30 functioning subscales. Conclusions Given the demonstrated association between financial toxicity and QOL, our study highlights the importance of addressing financial toxicity, particularly among patients receiving high-cost treatments. Implications for Psychosocial Providers: Providers should educate patients and their caregivers about cost-management techniques, link them with available resources, and provide psychosocial counseling to alleviate related distress.

First-line immune checkpoint inhibitor use in cisplatin-eligible patients with advanced urothelial carcinoma: a secular trend analysis.

Aim: Standard first-line treatment of advanced urothelial cell carcinoma involves cisplatin-based chemotherapy, with carboplatin or immune checkpoint inhibitor therapy (ICI) reserved for cisplatin-ineligible individuals. Methods: Using a large de-identified electronic health record-derived database of patients with advanced urothelial cell carcinoma in the USA, we examined trends in utilization of first-line systemic therapies in cisplatin-eligible patients from 1 January 2015 to 31 March 2018. Results: Among 1181 cisplatin-eligible patients, the quarterly proportion who received first-line ICI increased from 1 to 42% (ptrend <0.001), while the proportion who received cisplatin-based chemotherapy decreased from 53 to 33% (ptrend = 0.018). Patients receiving ICI were older than those receiving cisplatin (median age: 75 vs 68). Conclusion: Our analysis suggests rising off-label ICI use in cisplatin-eligible individuals, potentially because of ICI's favorable toxicity profile.

Phase 2 study of vascular endothelial growth factor trap for the treatment of metastatic thyroid cancer.

BACKGROUND: Several multitargeted tyrosine kinase inhibitors (TKIs) have demonstrated activity in patients with thyroid cancer that is refractory to radioactive iodine (RAI). The antitumor effect is attributed at least in part to the ability of these TKIs to inhibit angiogenesis in these vascular tumors. Vascular endothelial growth factor (VEGF) Trap (VT) is a recombinantly produced fusion protein consisting solely of human sequences for VEGF receptors 1 and 2 extracellular domains and human immunoglobulin 1. Evaluating VT in patients with thyroid cancer is reasonable considering the activity observed with TKIs targeting VEGF. METHODS: The current study was a single-institution, phase 2, Simon 2-stage design (21 to >41 patients) study based on the objective response rate and/or 6-month progression-free survival as the primary endpoints. Eligible patients were required to have progressive, RAI-refractory and/or [18 F]fludeoxyglucose-avid, recurrent and/or metastatic, nonmedullary, nonanaplastic thyroid cancer; disease that was measurable using Response Evaluation Criteria In Solid Tumors (RECIST) criteria; and adequate organ and bone marrow function. VT at a dose of 4 mg/kg intravenously was administered every 14 days. RESULTS: A total of 40 patients were included in the analysis. Of these patients, 24 had papillary thyroid cancer, 2 had follicular thyroid cancer, and 11 had Hurthle cell thyroid cancer. The final 3 tumors were classified as poorly differentiated. There were no complete and/or partial responses noted; 34 patients achieved stable disease and 6 patients experienced disease progression as their best response. Of the 34 patients with stable disease, 16 remained on the study for >6 months and 6 patients remained on the study for >12 months. The median duration on treatment was 4.1 months (range, 0.6-30.8 months). CONCLUSIONS: Unlike TKIs, which have shown responses in this setting, to the authors' knowledge there have been no responses observed with the use of single-agent VT to date. It does not appear to be a promising drug for the treatment of patients with thyroid cancer.

Phase 2 study evaluating the combination of sorafenib and temsirolimus in the treatment of radioactive iodine-refractory thyroid cancer.

BACKGROUND: Patients with recurrent and/or metastatic, radioactive iodine-refractory thyroid carcinoma have limited treatment options. Sorafenib, an oral kinase inhibitor, is approved by the US Food and Drug Administration for the treatment of radioactive iodine-refractory thyroid carcinoma, although it demonstrated low response rates (12.2%) as a single agent in the first-line setting. The objective of the current study was to determine whether adding the mammalian target of rapamycin inhibitor temsirolimus to sorafenib could improve on these results. METHODS: In this single-institution, phase 2 study, 36 patients with metastatic, radioactive iodine-refractory thyroid carcinoma of follicular origin received treatment with the combination of oral sorafenib (200 mg twice daily) and intravenous temsirolimus (25 mg weekly). The receipt of prior systemic treatment with cytotoxic chemotherapy and targeted therapy, including sorafenib, was permitted. The primary endpoint was the radiographic response rate. RESULTS: The best response was a partial response in 8 patients (22%), stable disease in 21 (58%), and progressive disease in 1 (3%). Six patients were not evaluable for a response. Patients who had received any prior systemic treatment had a response rate of 10% compared with 38% of those who had not received prior systemic treatment. One of 2 patients with anaplastic thyroid cancer had an objective response. The progression-free survival rate at 1 year was 30.5%. The most common grade 3 and 4 toxicities associated with sorafenib and temsirolimus included hyperglycemia, fatigue, anemia, and oral mucositis. CONCLUSIONS: Sorafenib and temsirolimus appear to be an active combination in patients with radioactive iodine-refractory thyroid carcinoma, especially in patients who received no prior treatment compared with historic data from single-agent sorafenib. Activity is also observed in patients who previously received sorafenib. This regimen warrants further investigation. Cancer 2017;123:4114-4121. © 2017 American Cancer Society.

The toxicity and efficacy of concomitant chemoradiotherapy in patients aged 70 years and older with oropharyngeal carcinoma in the intensity-modulated radiotherapy era.

BACKGROUND: Despite controversy surrounding its benefit, the use of concomitant chemoradiotherapy (CCRT) in patients with oropharyngeal squamous cell carcinoma (OPSCC) who are aged > 70 years is increasing. However, to the authors' knowledge, few studies to date have compared the outcomes of different systemic treatments in this population. METHODS: Records from 74 patients aged ≥ 70 years with stage III to stage IVB OPSCC who were undergoing CCRT from 2002 to 2013 at a single institution were reviewed. Patients were stratified according to the systemic therapy received, including cisplatin, carboplatin with either 5-fluorouracil or paclitaxel (CARB), or cetuximab to compare oncologic outcome and toxicity. RESULTS: The median follow-up was 36 months. The median age of the patients was 75.3 years (range, 70-91 years), with significantly older patients receiving cetuximab (P = .03). A total of 28, 20, and 26 patients, respectively, received CCRT with cisplatin, CARB, and cetuximab. RT interruptions of > 1 day were needed in 4% of patients receiving cisplatin, 20% of patients receiving CARB, and 15% of patients receiving cetuximab (P = .19). Unplanned hospitalizations during CCRT occurred in 25%, 55%, and 58%, respectively, of patients receiving cisplatin, CARB, and cetuximab (P = .03). There were 2 treatment-related deaths, both of which occurred among the patients who were treated with cetuximab. At 5 years, locoregional control was achieved in 100%, 88%, and 60% (P<.001), respectively, and the overall survival rate was 87%, 61%, and 47% (P = .03), respectively, among patients treated with cisplatin, CARB, and cetuximab. CONCLUSIONS: Toxicity from CCRT remains a challenge for older adults with OPSCC. Herein, the authors found no evidence that this toxicity was mitigated by treatment with cetuximab. Nevertheless, a subset of patients aged ≥70 years appear to tolerate cisplatin-based treatment with acceptable toxicity and excellent outcomes. Further identification of this patient subgroup is crucial to optimize therapy for older patients with OPSCC. Cancer 2017;123:1345-1353. © 2016 American Cancer Society.

Overuse of Health Care Services in the Management of Cancer: A Systematic Review.

BACKGROUND: Overuse, the provision of health services for which harms outweigh the benefits, results in suboptimal patient care and may contribute to the rising costs of cancer care. We performed a systematic review of the evidence on overuse in oncology. METHODS: We searched Medline, EMBASE, the Cochrane Library, Web of Science, SCOPUS databases, and 2 grey literature sources, for articles published between December 1, 2011 and March 10, 2017. We included publications from December 2011 to evaluate the literature since the inception of the ABIM Foundation's Choosing Wisely initiative in 2012. We included original research articles quantifying overuse of any medical service in patients with a cancer diagnosis when utilizing an acceptable standard to define care appropriateness, excluding studies of cancer screening. One of 4 investigator reviewed titles and abstracts and 2 of 4 reviewed each full-text article and extracted data. Methodology used PRISMA guidelines. RESULTS: We identified 59 articles measuring overuse of 154 services related to imaging, procedures, and therapeutics in cancer management. The majority of studies addressed adult or geriatric patients (98%) and focused on US populations (76%); the most studied services were diagnostic imaging in low-risk prostate and breast cancer. Few studies evaluated active cancer therapeutics or interventions aimed at reducing overuse. Rates of overuse varied widely among services and among studies of the same service. CONCLUSIONS: Despite recent attention to overuse in cancer, evidence identifying areas of overuse remains limited. Broader investigation, including assessment of active cancer treatment, is critical for identifying improvement targets to optimize value in cancer care.

Variation in use of postoperative chemoradiation following surgery for T1 and T2 oropharyngeal squamous cell carcinoma; National Cancer Database.

BACKGROUND AND OBJECTIVES: Primary surgical treatment of patients with early T-classification (T1-T2) oropharyngeal squamous cell carcinoma (OPSCC) has increased. We sought to determine how often these patients receive postoperative chemoradiation (CRT). METHODS: Patients with T1-T2 OPSCC in the National Cancer Database who underwent primary surgery were evaluated for receipt of postoperative CRT. Postoperative CRT use was examined among patients with high risk factors (positive margins and/or extracapsular spread [ECS]), intermediate risk factors (negative margins, no ECS, and either pT3-4 and/or N2-N3), and no apparent risk factors. RESULTS: Of 4833 patients with T1-T2 OPSCC who underwent primary surgery, 43% had high risk pathologic factors, of whom only 63% received postoperative CRT. Another 31% had no apparent risk factors, of whom 16% nonetheless received postoperative CRT. On multivariable analysis, in addition to tumor and demographic factors, patients treated at community hospitals were more likely to receive postoperative CRT (O.R. 1.41 C.I. 1.18-1.87, P = 0.001). CONCLUSIONS: Variation in postoperative CRT use indicates a lack of consensus and/or knowledge about its benefits and indications. Usage of postoperative CRT regardless of pathologic risk factors suggests an area where future efforts at implementation of best practices may be targeted.

Increase in primary surgical treatment of T1 and T2 oropharyngeal squamous cell carcinoma and rates of adverse pathologic features: National Cancer Data Base.

BACKGROUND: There has been increasing interest in the primary surgical treatment of patients with early T classification (T1-T2) oropharyngeal squamous cell carcinoma (OPSCC), with the stated goal of de-escalating or avoiding adjuvant treatment. Herein, the authors sought to determine the degree to which this interest has translated into changes in practice patterns, and the rates of adverse postoperative pathologic features. METHODS: Patients with T1 to T2 OPSCC in the National Cancer Data Base who were treated from 2004 through 2013 were categorized as receiving primary surgical or primary radiation-based treatment. Trends in treatment selection and factors related to the selection of primary surgery were examined. The rates of adverse pathologic features including positive surgical margins, extracapsular spread (ECS), and advanced T and N classifications after surgery were analyzed. RESULTS: Of 8768 patients with T1 to T2 OPSCC, 68% underwent primary surgical treatment, increasing from 56% in 2004 to 82% in 2013 (P<.0001). The highest versus lowest volume hospitals treated 78% versus 59% of patients with primary surgery (odds ratio, 2.23; 95% confidence interval, 1.55-3.22 [P<.0001]). Higher lymph node classification was found to be predictive of lower rates of primary surgery, but the majority of patients with clinical N2/N3 disease underwent primary surgery. Among patients treated with surgery, positive surgical margins were present in 24% and ECS in 25% of patients. The rate of positive surgical margins decreased over time (P<.0001) and was observed less often at high-volume centers (P<.0001). Among candidates for single-modality therapy (those with clinical T1-T2/N0-N1 disease), 33% had positive surgical margins and/or ECS and 47% had at least 1 adverse feature (T3-T4 disease, N2-N3 disease, positive surgical margins, and/or ECS). CONCLUSIONS: Primary surgical treatment among patients with early T classification OPSCC has become more widespread. Cancer 2016;122:1523-32. © 2016 American Cancer Society.

Treatment-related toxicities in older adults with head and neck cancer: A population-based analysis.

BACKGROUND: Despite advantages in terms of cancer control and organ preservation, the benefits of chemotherapy and radiation therapy (CTRT) may be offset by potentially severe treatment-related toxicities, particularly in older patients. The objectives of this study were to assess the types and frequencies of toxicities in older adults with locally or regionally advanced head and neck squamous cell carcinoma (HNSCC) who were receiving either primary CTRT or radiation therapy (RT) alone. METHODS: With Surveillance, Epidemiology, and End Results cancer registry data linked with Medicare claims, patients who were 66 years old or older with locally advanced HNSCC, were diagnosed from 2001 to 2009, and received CTRT or RT alone were identified. Differences in the frequency of toxicity-related hospital admissions and emergency room visits as well as feeding tube use were examined, and controlling for demographic and disease characteristics, this study estimated the impact of chemotherapy on the likelihood of toxicity. RESULTS: Among patients who received CTRT (n = 1502), 62% had a treatment-related toxicity, whereas 46% of patients who received RT alone (n = 775) did. When the study controlled for demographic and disease characteristics, CTRT patients were twice as likely to experience an acute toxicity in comparison with their RT-only peers. Fifty-five percent of CTRT patients had a feeding tube placed during or after treatment, whereas 28% of the RT-only group did. CONCLUSIONS: In this population-based cohort of older adults with HNSCC, the rates of acute toxicities and feeding tube use in patients receiving CTRT were considerable. It is possible that for certain older patients, the potential benefit of adding chemotherapy to RT does not outweigh the harms of this combined-modality therapy.

Causes of death in long-term survivors of head and neck cancer.

BACKGROUND: Survivors of head and neck squamous cell carcinoma (HNSCC) face excess mortality from multiple causes. METHODS: We used the population-based Surveillance, Epidemiology, and End Results (SEER) cancer registry data to evaluate the causes of death in patients with nonmetastatic HNSCC diagnosed between 1992 and 2005 who survived at least 3 years from diagnosis (long-term survivors). We used competing-risks proportional hazards regression to estimate probabilities of death from causes: HNSCC, second primary malignancy (SPM) excluding HNSCC, cardiovascular disease, and other causes. RESULTS: We identified 35,958 three-year survivors of HNSCC with a median age at diagnosis of 60 years (range = 18-100 years) and a median follow-up of 7.7 years (range = 3-18 years). There were 13,120 deaths during the study period. Death from any cause at 5 and 10 years was 15.4% (95% confidence interval [CI] = 15.0%-15.8%) and 41.0% (95% CI = 40.4%-41.6%), respectively. There were 3852 HNSCC deaths including both primary and subsequent head and neck tumors. The risk of death from HNSCC was greater in patients with nasopharynx or hypopharynx cancer and in patients with locally advanced disease. SPM was the leading cause of non-HNSCC death, and the most common sites of SPM death were lung (53%), esophagus (10%), and colorectal (5%) cancer. CONCLUSIONS: Many long-term HNSCC survivors die from cancers other than HNSCC and from noncancer causes. Routine follow-up care for HNSCC survivors should expand beyond surveillance for recurrent and new head and neck cancers.

Survivorship care plans: is there buy-in from community oncology providers?

BACKGROUND: The Institute of Medicine recommended that survivors of cancer and their primary care providers receive survivorship care plans (SCPs) to summarize cancer treatment and plan ongoing care. However, the use of SCPs remains limited. METHODS: Oncology providers at 14 National Cancer Institute Community Cancer Centers Program hospitals completed a survey regarding their perceptions of SCPs, including barriers to implementation, strategies for implementation, the role of oncology providers, and the importance of topics in SCPs (diagnosis, treatment, recommended ongoing care, and the aspects of ongoing care that the oncology practice will provide). RESULTS: Among 245 providers (response rate of 70%), 52% reported ever providing any component of an SCP to patients. The most widely reported barriers were lack of personnel and time to create SCPs (69% and 64% of respondents, respectively). The most widely endorsed strategy among those using SCPs was the use of a template with prespecified fields; 94% of those who used templates found them helpful. For each topic of an SCP, although 87% to 89% of oncology providers believed it was very important for primary care providers to receive the information, only 58% to 65% of respondents believed it was very important for patients to receive the information. Furthermore, 33% to 38% of respondents reported mixed feelings regarding whether it was the responsibility of oncology providers to provide SCPs. CONCLUSIONS: Practices need additional resources to overcome barriers to implementing SCPs. We found resistance toward SCPs, particularly the perceived value for the survivor and the idea that oncology providers are responsible for SCP dissemination.

Synchronous cancers in patients with head and neck cancer: risks in the era of human papillomavirus-associated oropharyngeal cancer.

BACKGROUND: Second primary malignancies (SPMs) are the leading cause of death in survivors of head and neck squamous cell carcinoma (HNSCC). Synchronous SPMs are of significant clinical interest because they potentially can be identified by screening procedures at the time of diagnosis of the index cancer. Recently, human papillomavirus (HPV) has emerged as a distinct risk factor for oropharyngeal head and neck squamous cell carcinoma (HNSCC), differing from classic tobacco/alcohol-associated HNSCC, suggesting that there also may be distinct patterns of synchronous SPMs. METHODS: The authors performed a population-based cohort study in 64,673 patients in the National Cancer Institute Surveillance, Epidemiology, and End Results registry (1979-2008), defining risks of synchronous SPM in patients with HNSCC who were diagnosed before and after the emergence of prevalent HPV-associated oropharyngeal HNSCC. Excess risk was calculated using standardized incidence ratios (SIR) and excess absolute risk per 100 patients. RESULTS: Among patients with HNSCC, the SIR of synchronous SPM was 5.0, corresponding to 2.62 excess cases per 100 patients. The site with the highest excess risk of a second cancer was the head and neck (SIR, 41.4), followed by the esophagus (SIR, 21.8), and lung (SIR, 7.4). The risk of synchronous SPM changed markedly over time for patients with oropharyngeal HNSCC. In the 1970s and 1980s, oropharyngeal cancers carried the highest risk of SPM. Risk began to dramatically decline in the 1990s; and currently, oropharyngeal cancers carry the lowest risk of synchronous SPM. CONCLUSIONS: The current data are consistent with the etiologic shift of oropharyngeal HNSCC, from a primarily tobacco-associated malignancy associated with significant field cancerization of the upper aerodigestive mucosa, to a malignancy primarily caused by oncogenic human papillomavirus.

Augmenting control arms with real-world data for cancer trials: Hybrid control arm methods and considerations.

Background: Hybrid controlled trials with real-world data (RWD), where the control arm is composed of both trial and real-world patients, could facilitate research when the feasibility of randomized controlled trials (RCTs) is challenging and single-arm trials would provide insufficient information. Methods: We propose a frequentist two-step borrowing method to construct hybrid control arms. We use parameters informed by a completed randomized trial in metastatic triple-negative breast cancer to simulate the operating characteristics of dynamic and static borrowing methods, highlighting key trade-offs and analytic decisions in the design of hybrid studies. Results: Simulated data were generated under varying residual-bias assumptions (no bias: HRRWD = 1) and experimental treatment effects (target trial scenario: HRExp = 0.78). Under the target scenario with no residual bias, all borrowing methods achieved the desired 88% power, an improvement over the reference model (74% power) that does not borrow information externally. The effective number of external events tended to decrease with higher bias between RWD and RCT (i.e. HRRWD away from 1), and with weaker experimental treatment effects (i.e. HRExp closer to 1). All dynamic borrowing methods illustrated (but not the static power prior) cap the maximum Type 1 error over the residual-bias range considered. Our two-step model achieved comparable results for power, type 1 error, and effective number of external events borrowed compared to other borrowing methodologies. Conclusion: By pairing high-quality external data with rigorous simulations, researchers have the potential to design hybrid controlled trials that better meet the needs of patients and drug development.

Enhancing Radioiodine Incorporation in BRAF-Mutant, Radioiodine-Refractory Thyroid Cancers with Vemurafenib and the Anti-ErbB3 Monoclonal Antibody CDX-3379: Results of a Pilot Clinical Trial.

Background: Oncogenic activation of mitogen-activated protein kinase (MAPK) signaling is associated with radioiodine refractory (RAIR) thyroid cancer. Preclinical models suggest that activation of the receptor tyrosine kinase erbB-3 (HER3) mitigates the MAPK pathway inhibition achieved by BRAF inhibitors in BRAFV600E mutant thyroid cancers. We hypothesized that combined inhibition of BRAF and HER3 using vemurafenib and the human monoclonal antibody CDX-3379, respectively, would potently inhibit MAPK activation and restore radioactive iodine (RAI) avidity in patients with BRAF-mutant RAIR thyroid cancer. Methods: Patients with BRAFV600E RAIR thyroid cancer were evaluated by thyrogen-stimulated iodine-124 (124I) positron emission tomography-computed tomography (PET/CT) at baseline and after 5 weeks of treatment with oral vemurafenib 960 mg twice daily alone for 1 week, followed by vemurafenib in combination with 1000 mg of intravenous CDX-3379 every 2 weeks. Patients with adequate 124I uptake on the second PET/CT then received therapeutic radioactive iodine (131I) with vemurafenb+CDX-3379. All therapy was discontinued two days later. Treatment response was monitored by serum thyroglobulin measurements and imaging. The primary endpoints were safety and tolerability of vemurafenib+CDX-3379, as well as the proportion of patients after vemurafenb+CDX-3379 therapy with enhanced RAI incorporation warranting therapeutic 131I. Results: Seven patients were enrolled; six were evaluable for the primary endpoints. No grade 3 or 4 toxicities related to CDX-3379 were observed. Five patients had increased RAI uptake after treatment; in 4 patients this increased uptake warranted therapeutic 131I. At 6 months, 2 patients achieved partial response after 131I and 2 progression of disease. Next-generation sequencing of 5 patients showed that all had co-occurring telomerase reverse transcriptase promoter alterations. A deleterious mutation in the SWItch/Sucrose Non-Fermentable (SWI/SNF) gene ARID2 was discovered in the patient without enhanced RAI avidity after therapy and an RAI-resistant tumor from another patient that was sampled off-study. Conclusions: The endpoints for success were met, providing preliminary evidence of vemurafenib+CDX-3379 safety and efficacy for enhancing RAI uptake. Preclinical data and genomic profiling in this small cohort suggest SWI/SNF gene mutations should be investigated as potential markers of resistance to redifferentiation strategies. Further evaluation of vemurafenib+CDX-3379 as a redifferentiation therapy in a larger trial is warranted (ClinicalTrials.gov: NCT02456701).

The future of mammography: radiology residents' experiences, attitudes, and opinions.

OBJECTIVE: The objective of our study was to assess the experiences and preferences of radiology residents with respect to breast imaging. MATERIALS AND METHODS: We surveyed radiology residents at 26 programs in New York and New Jersey. Survey topics included plans for subspecialty training, beliefs, and attitudes toward breast imaging and breast cancer screening and the likelihood of interpreting mammography in the future. RESULTS: Three hundred forty-four residents completed the survey (response rate, 62%). The length of time spent training in breast imaging varied from no dedicated time (37%) to 1-8 weeks (40%) to more than 9 weeks (23%). Most respondents (97%) agreed that mammography is important to women's health. More than 85% of residents believed that mammography should be interpreted by breast imaging specialists. Respondents shared negative views about mammography, agreeing with statements that the field was associated with a high risk of malpractice (99%), stress (94%), and low reimbursement (68%). Respondents endorsed several positive attributes of mammography, including job availability (97%), flexible work schedules (94%), and few calls or emergencies (93%). Most radiology residents (93%) said that they were likely to pursue subspecialty training, and 7% expressed interest in breast imaging fellowships. CONCLUSION: Radiology residents' negative and positive views about mammography seem to be independent of time spent training in mammography and of future plans to pursue fellowship training in breast imaging. Systematic assessment of the plans and preferences of radiology residents can facilitate the development of strategies to attract trainees to careers in breast imaging.

State-of-the-art issues in Hodgkin's lymphoma survivorship.

The prognosis of Hodgkin's lymphoma (HL) has markedly improved as management strategies evolved. In the modern era, less than 15% of patients with early-stage, non-bulky HL will relapse, and less than one third of those with advanced disease will relapse. As therapy for HL intensified, and as disease-related outcomes improved, the impact of the late effects of therapy has become increasingly important. There is a growing body of literature describing the late morbidity experienced by survivors of HL, including risks of second primary malignancy, cardiac disease, pulmonary disease, and endocrine dysfunction. Additionally, the impact of disease and treatment on psychosocial function and quality of life has been a subject of investigation, with survivors often suffering from impairment. An understanding of these risks and the management implications inherent to them is central to the care of survivors of HL.

Letting the GENIE Out of Its Bottle: Examining the Potential of Real-World Clinicogenomic Data.

In this issue, Smyth and colleagues investigate the natural history of AKT1-mutant metastatic breast cancer using the AACR Project GENIE, a novel research platform comprised of real-world, clinicogenomic data. A rare subset of tumors, AKT1-mutant breast cancers demonstrated similar clinical and demographic characteristics and overall survival as AKT1-wild-type tumors, but a longer duration of therapy on mTOR inhibitors.See related article by Smyth et al., p. 526.

Using electronic health record data to identify comparator populations for comparative effectiveness research.

Electronic health records (EHRs) can define real world patient populations with high levels of clinical specificity, potentially addressing some of the shortcomings of other types of real world data (RWD) when informing decisions about the comparative effectiveness of medical technologies. An important but under-recognized concern for EHR-derived RWD, however, is that the rich clinical data permits creation of very homogenous subpopulations from the larger group of eligible patients, thereby reducing the representativeness of the cohort relative to clinical practice. In this article, we discuss the tradeoffs between choosing clinical specificity versus representativeness in population sampling for comparative effectiveness research. Using EHR-derived RWD, we provide an example in non-small cell lung cancer to illustrate the concepts, showing wide variation in outcomes among potential comparator cohorts. We close with several recommendations for selecting comparator populations from EHRs that address the balance between matching clinical guidelines and capturing practice variability in comparative effectiveness research.