Sociodemographic and clinical characteristics associated with multiple biologic failure in psoriasis: A 2015-2022 prospective cohort analysis of the CorEvitas psoriasis registry.

BACKGROUND: Psoriasis patients with poor therapeutic response to multiple biologic agents are not well-characterized. OBJECTIVE: To describe the characteristics associated with development of multiple biologic failure (MBF) versus good clinical response (GR) to the first biologic. METHODS: This prospective cohort analysis evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for ≥24 months. Multivariable logistic regression identified sociodemographic, clinical, and patient-reported outcomes that differed between MBF (discontinued ≥2 biologics of different classes, each used for ≥90 days, due to inadequate efficacy) and GR (continued use of first biologic for ≥2 years) patients. RESULTS: One thousand thirty-nine patients were analyzed (490 GR [47.2%], 65 MBF [6.3%]). Female sex, shorter psoriasis duration, earlier year of biologic initiation, prior nonbiologic systemic therapy use, history of hyperlipidemia, and Medicaid insurance were significantly associated with MBF, though the latter 2 variables exhibited wider confidence intervals, indicating a lower level of support. The first-to-second biologic sequence most observed with MBF was Tumor necrosis factor-α inhibitor to IL-17 inhibitor use. LIMITATIONS: Biologic adherence between visits was not evaluated. CONCLUSION: Approximately 6% of psoriasis patients met MBF criteria. The results identify characteristics associated with MBF that may distinguish patients warranting more frequent follow-up.

Embedding a genetic counselor into oncology clinics improves testing rates and timeliness for women with ovarian cancer.

OBJECTIVE: Germline genetic testing is crucial to the care of ovarian cancer patients, and as part of the guideline-based care for ovarian cancer patient's adherence to this recommendation has been low. We sought to determine whether embedding a genetic counselor (GC) within a medical and gynecologic oncology clinic would increase testing rates and improve the timeliness of testing. METHODS: Prospective cohort study of 358 ovarian cancer patients seen by medical and gynecologic oncologists between 2013 and 2015. Rates of referrals, completion of counseling, and genetic testing and timeliness of counseling were abstracted before and after a GC was embedded in the clinic in 2014. An additional year of data (2015) was collected to evaluate sustainability of the intervention. RESULTS: Between 2013 and 2015, 88-92% of women were referred for genetic testing, but in 2013 only 66% completed counseling and 61% were tested. After a GC was embedded in the clinic in 2014, more than 80% of referred women completed counseling and germline genetic testing. Time to genetic counseling also decreased from a median of 107 to 40 days, irrespective of age and cancer family history (p < 0.01). CONCLUSIONS: Embedding a GC into the workflow for ovarian cancer patients is an effective way of improving access to genetic counseling, testing rates, and the timeliness of testing.

Variation in Use of High-Cost Technologies for Palliative Radiation Therapy by Radiation Oncologists.

BACKGROUND: Understanding the sources of variation in the use of high-cost technologies is important for developing effective strategies to control costs of care. Palliative radiation therapy (RT) is a discretionary treatment and its use may vary based on patient and clinician factors. METHODS: Using data from the SEER-Medicare linked database, we identified patients diagnosed with metastatic lung, prostate, breast, and colorectal cancers in 2010 through 2015 who received RT, and the radiation oncologists who treated them. The costs of radiation services for each patient over a 90-day episode were calculated, and radiation oncologists were assigned to cost quintiles. The use of advanced technologies (eg, intensity-modulated radiation, stereotactic RT) and the number of RT treatments (eg, any site, bone only) were identified. Multivariable random-effects models were constructed to estimate the proportion of variation in the use of advanced technologies and extended fractionation (>10 fractions) that could be explained by patient fixed effects versus physician random effects. RESULTS: We identified 37,361 patients with metastatic lung cancer, 3,684 with metastatic breast cancer, 5,323 with metastatic prostate cancer, and 8,726 with metastatic colorectal cancer, with 34%, 27%, 22%, and 9% receiving RT within the first year, respectively. The use of advanced technologies and extended fractionation was associated with higher costs of care. Compared with the patient case-mix, physician variation accounted for a larger proportion of the variation in the use of advanced technologies for palliative RT and the use of extended fractionation. CONCLUSIONS: Differences in radiation oncologists' practice and choices, rather than differences in patient case-mix, accounted for a greater proportion of the variation in the use of advanced technologies and high-cost radiation services.

Drug survival of ixekizumab, TNF inhibitors, and other IL-17 inhibitors in real-world patients with psoriasis: The Corrona Psoriasis Registry.

To compare drug survival of ixekizumab to other IL-17 inhibitors (IL-17i) and TNF inhibitors (TNFi) among patients with psoriasis (PsO) in a real-world setting. Participants included adult PsO patients enrolled in the Corrona Psoriasis Registry who initiated ixekizumab, TNFi, or other IL-17i between 16 March 2016 to 10 August 2019 and completed ≥1 follow-up visit. Multivariable adjusted hazard ratios (HR) were calculated to estimate the risk for drug discontinuation in the ixekizumab group relative to the other drugs. Among the 1604 drug initiations, 552 initiated ixekizumab, 450 initiated TNFi, and 602 initiated other IL-17i. Mean age was 51 years, 49% were women, and 52% were obese (BMI > 30). Ixekizumab patients had a higher proportion of patients with PASI >12 at drug initiation (24%) than TNFi (15%) and other IL-17i (19%). Over a median of 11 months of follow-up, 723/1604 (45%) drug discontinuations occurred. Persistence of ixekizumab, TNFi, and other IL-17i at 24-months were 68%, 33%, and 46%, among biologic-naïve patients (n = 543), and 46%, 23%, and 36%, for biologic-experienced patients (n = 1061), respectively. Ixekizumab patients had a 64% lower risk of discontinuation vs TNFi (HR = 0.36; 95% CI 0.27-0.47) and a 31% lower risk vs other IL-17i (HR = 0.69, 95% CI 0.55-0.87) after adjustment for biologic experience and other covariates. HRs were similar when limited to patients with moderate-to-severe PsO (BSA > 3, PASI > 3, and IGA > 1, n = 1076) at initiation. In our study of real-world patients with PsO, initiators of ixekizumab had more prolonged drug survival than both initiators of TNFi and other IL-17i up to 2 years of follow-up.

Unrealistic parental expectations for cure in poor-prognosis childhood cancer.

BACKGROUND: Many parents of children with advanced cancer pursue curative goals when cure is no longer possible. To the authors' knowledge, no pediatric studies to date have prospectively evaluated prognosis communication or influences on decision making in poor-prognosis childhood cancer. METHODS: The authors conducted a prospective cohort study at 9 pediatric cancer centers that enrolled 95 parents of children with recurrent or refractory, high-risk neuroblastoma (63% of those who were approached), a condition for which cure rarely is achieved. Parents were surveyed regarding the child's likelihood of cure; their primary goal of care; the child's symptoms, suffering, and quality of life; and regret concerning the last treatment decision. Medical records identified care and treatment decisions. RESULTS: Only 26% of parents recognized that the chance of cure was <25%. When asked to choose a single most important goal of care, approximately 72% chose cure, 10% chose longer life, and 18% chose quality of life. Parents were more likely to prioritize quality of life when they recognized the child's poor prognosis (P = .002). Approximately 41% of parents expressed regret about the most recent treatment decision. Parents were more likely to experience regret if the child had received higher intensity medical care (odds ratio [OR], 3.14; 95% CI, 1.31-7.51), experienced suffering with limited benefit from the most recent treatment (OR, 4.78; 95% CI, 1.16-19.72), or experienced suffering from symptoms (OR, 2.91; 95% CI, 1.18-7.16). CONCLUSIONS: Parents of children with poor-prognosis cancer frequently make decisions based on unrealistic expectations. New strategies for effective prognosis communication are needed.

Overuse of Diagnostic Brain Imaging Among Patients With Stage IA Non-Small Cell Lung Cancer.

BACKGROUND: Among patients diagnosed with stage IA non-small cell lung cancer (NSCLC), the incidence of occult brain metastasis is low, and several professional societies recommend against brain imaging for staging purposes. The goal of this study was to characterize the use of brain imaging among Medicare patients diagnosed with stage IA NSCLC. METHODS: Using data from linked SEER-Medicare claims, we identified patients diagnosed with AJCC 8th edition stage IA NSCLC in 2004 through 2013. Patients were classified as having received brain imaging if they underwent head CT or brain MRI from 1 month before to 3 months after diagnosis. We identified factors associated with receipt of brain imaging using multivariable logistic regression. RESULTS: Among 13,809 patients with stage IA NSCLC, 3,417 (25%) underwent brain imaging at time of diagnosis. The rate of brain imaging increased over time, from 23.5% in 2004 to 28.7% in 2013 (P=.0006). There was significant variation in the use of brain imaging across hospital service areas, with rates ranging from 0% to 64.0%. Factors associated with a greater likelihood of brain imaging included older age (odds ratios [ORs] of 1.16 for 70-74 years, 1.13 for 75-79 years, 1.31 for 80-84 years, and 1.46 for ≥85 years compared with 65-69 years; all P<.05), female sex (OR, 1.09; P<.05), black race (OR 1.23; P<.05), larger tumor size (ORs of 1.23 for 11-20 mm and 1.28 for 21-30 mm tumors vs 1-10 mm tumors; all P<.05), and higher modified Charlson-Deyo comorbidity score (OR, 1.28 for score >1 vs score of 0; P<.05). CONCLUSIONS: Roughly 1 in 4 patients with stage IA NSCLC received brain imaging at the time of diagnosis despite national recommendations against the practice. Although several patient factors are associated with receipt of brain imaging, there is significant geographic variation across the United States. Closer adherence to clinical guidelines is likely to result in more cost-effective care.

Impact of pre-diagnosis depressive symptoms and health-related quality of life on treatment choice for ductal carcinoma in situ and stage I breast cancer in older women.

PURPOSE: To examine whether pre-diagnosis patient-reported health-related quality of life (HRQOL) and depressive symptoms are associated with local treatment for older women with ductal carcinoma in situ (DCIS) and stage I breast cancer (BC). METHODS: Using the SEER-MHOS dataset, we identified women ≥ 65 years old with DCIS or stage I BC diagnosed 1998-2011 who completed surveys ≤ 24 months before diagnosis. Depressive symptoms were measured by major depressive disorder (MDD) risk and HRQOL was measured by Physical and Mental Component Summary scores (PCS and MCS, respectively) of the SF-36/VR-12. Associations with treatment choice (breast-conserving surgery [BCS] and radiation therapy [RT], BCS alone, mastectomy) were assessed with multivariable multinomial logistic regression, controlling for patient characteristics. RESULTS: We identified 425 women with DCIS and 982 with stage I BC. Overall, 20.4% endorsed depressive symptoms placing them at risk for MDD pre-diagnosis; mean MCS and PCS scores were 52.3 (SD = 10.1) and 40.5 (SD = 11.5), respectively. Among women with DCIS, those at risk for MDD were more likely to receive BCS (adjusted odds ratio [AOR] 2.04, 95% CI 1.04-4.00, p = 0.04) or mastectomy (AOR 1.88, 95% CI 0.91-3.86, p = 0.09) compared to BCS + RT. For DCIS, MCS score was not associated with treatment; higher PCS score was associated with decreased likelihood of receiving mastectomy versus BCS + RT (AOR 0.71 per 10-point increase, 95% CI 0.54-0.95, p = 0.02). For BC, none of the measures were significantly associated with treatment. CONCLUSION: Older women at risk for MDD before DCIS diagnosis were less likely to receive RT after BCS, compared to BCS alone or mastectomy.

Psychological outcomes related to exome and genome sequencing result disclosure: a meta-analysis of seven Clinical Sequencing Exploratory Research (CSER) Consortium studies.

PURPOSE: As exome and genome sequencing (ES/GS) enters the clinic, there is an urgent need to understand the psychological effects of test result disclosure. Through a Clinical Sequencing Exploratory Research (CSER), phase 1 (CSER1) Consortium collaboration, we evaluated participants' psychological outcomes across multiple clinical settings. METHODS: We conducted a random effects meta-analysis of state anxiety (Hospital Anxiety and Depression Scale [HADS]/Generalized Anxiety Disorder 7-item), depressive symptoms (HADS/Personal Health Questionnaire 9-item), and multidimensional impact (i.e., test-related distress, uncertainty and positive impact: modified Multidimensional Impact of Cancer Risk Assessment/Feelings About Genomic Testing Results scale). RESULTS: Anxiety and depression did not increase significantly following test result disclosure. Meta-analyses examining mean differences from pre- to postdisclosure revealed an overall trend for a decrease in participants' anxiety. We observed low levels of test-related distress and perceptions of uncertainty in some populations (e.g., pediatric patients) and a wide range of positive responses. CONCLUSION: Our findings across multiple clinical settings suggest no clinically significant psychological harms from the return of ES/GS results. Some populations may experience low levels of test-related distress or greater positive psychological effects. Future research should further investigate the reasons for test-related psychological response variation.

Outcomes of secondary cytoreductive surgery for patients with platinum-sensitive recurrent ovarian cancer.

BACKGROUND: Most women with advanced epithelial ovarian cancer develop recurrent disease, despite maximal surgical cytoreduction and adjuvant platinum-based chemotherapy. In observational studies, secondary cytoreductive surgery has been associated with improved survival; however its use is controversial, because there are concerns that the improved outcomes may reflect selection bias rather than the superiority of secondary surgery. OBJECTIVE: To compare the overall survival of women with platinum-sensitive recurrent ovarian cancer treated at National Cancer Institute-designated cancer centers who receive secondary surgery vs chemotherapy. STUDY DESIGN: This retrospective cohort study included women from 6 National Cancer Institute-designated cancer centers diagnosed with platinum-sensitive recurrent ovarian cancer between January 1, 2004, and December 31, 2011. The primary outcome was overall survival. Propensity score matching was used to compare similar women who received secondary surgery vs chemotherapy. Additional analyses examined how these findings may be influenced by the prevalence of unobserved confounders at the time of recurrence. RESULTS: Among 626 women, 146 (23%) received secondary surgery and 480 (77%) received chemotherapy. In adjusted analyses, patients who received secondary surgery were younger (P = 0.001), had earlier-stage disease at diagnosis (P = 0.002), and had longer disease-free intervals (P < 0.001) compared with those receiving chemotherapy. In the propensity score-matched groups (n = 244 patients), the median overall survival was 54 months in patients who received secondary surgery and 33 months in those treated with chemotherapy (P < 0.001). Among patients who received secondary surgery, 102 (70%) achieved optimal secondary cytoreduction. There were no significant differences in complication rates between the 2 groups. In sensitivity analyses, the survival advantage associated with secondary surgery could be explained by the presence of more multifocal recurrences (if 4.3 times more common), ascites (if 2.7 times more common), or carcinomatosis (if 2.1 times more common) among patients who received chemotherapy instead of secondary surgery. CONCLUSION: Patients with platinum-sensitive recurrent ovarian cancer who received secondary surgery had favorable surgical characteristics and were likely to have minimal residual disease following secondary surgery. These patients had a superior median overall survival compared with patients who received chemotherapy, although unmeasured confounders may explain this observed difference.

Mortality After Invasive Second Breast Cancers Following Prior Radiotherapy for DCIS.

BACKGROUND: Women with a history of ductal carcinoma in situ (DCIS) are at increased risk for developing a second breast cancer (SBC). A prior meta-analysis of randomized studies of radiotherapy (RT) for DCIS has shown a trend toward increased breast cancer-specific mortality after SBC, but it did not have the power needed to detect a significant difference, due to a limited number of recurrences. This study sought to evaluate the impact of RT for DCIS on mortality after SBC in a larger cohort. PATIENTS AND METHODS: Using the SEER database, 3,407 patients were identified who received breast-conserving therapy with or without RT for primary DCIS in 2000 through 2013 and subsequently developed a stage I-III invasive SBC within the same time period. Fine-Gray competing risk models were used to study the association between receipt of RT and mortality after SBC. RESULTS: Prior RT was found to be associated with higher rates of breast cancer-specific mortality (hazard ratio [HR], 1.70; 95% CI, 1.18-2.45; P=.005), even after controlling for cancer stage. Interaction analysis suggested that this risk trended higher in patients with ipsilateral versus contralateral SBC (HR, 2.07 vs 1.26; P=.16). Furthermore, compared with patients who developed contralateral SBC, those with ipsilateral SBC were younger (P<.001) and more often lacked estrogen receptor expression (P<.001). CONCLUSIONS: Patients who previously received RT for DCIS had higher mortality after developing an invasive SBC than those who did not receive RT. This finding may have implications for initial treatment decisions in the management of DCIS.

Intended and unintended consequences: Ethics, communication, and prognostic disclosure in pediatric oncology.

BACKGROUND: The majority of patients desire all available prognostic information, but some physicians hesitate to discuss prognosis. The objective of the current study was to examine outcomes of prognostic disclosure among the parents of children with cancer. METHODS: The authors surveyed 353 parents of children with newly diagnosed cancer at 2 tertiary cancer centers, and each child's oncologist. Using multivariable logistic regression, the authors assessed associations between parental report of elements of prognosis discussions with the oncologist (quality of information/communication and prognostic disclosure) and potential consequences of these discussions (trust, hope, peace of mind, prognostic understanding, depression, and anxiety). Analyses were stratified by oncologist-reported prognosis. RESULTS: Prognostic disclosure was not found to be associated with increased parental anxiety, depression, or decreased hope. Among the parents of children with less favorable prognoses (<75% chance of cure), the receipt of high-quality information from the oncologist was associated with greater peace of mind (odds ratio [OR], 5.23; 95% confidence interval [95% CI], 1.81-15.16) and communication-related hope (OR, 2.54; 95% CI, 1.00-6.40). High-quality oncologist communication style was associated with greater trust in the physician (OR, 2.45; 95% CI, 1.09-5.48) and hope (OR, 3.01; 95% CI, 1.26-7.19). Accurate prognostic understanding was less common among the parents of children with less favorable prognoses (OR, 0.39; 95% CI, 0.17-0.88). Receipt of high-quality information, high-quality communication, and prognostic disclosure were not found to be significantly associated with more accurate prognostic understanding. CONCLUSIONS: The results of the current study demonstrate no evidence that disclosure is associated with anxiety, depression, or decreased hope. Communication processes may increase peace of mind, trust, and hope. It remains unclear how best to enhance prognostic understanding. Cancer 2018;124:1232-41. © 2017 American Cancer Society.

Parental distress and desire for information regarding long-term implications of pediatric cancer treatment.

BACKGROUND: Parents of children with cancer have unmet information needs regarding future limitations resulting from cancer or its treatment. Prior research has demonstrated that, in early care discussions, clinicians focus on the acute effects of therapy rather than long-term limitations, partly due to worries of causing distress. The validity of concerns regarding distress is unknown. In the current study, the authors evaluated parental distress associated with information regarding future limitations, and the extent to which distress is associated with information preferences. METHODS: The authors surveyed 355 parents of children with cancer within 3 months of diagnosis, and the children's physicians at Dana-Farber Cancer Institute/Boston Children's Cancer and Blood Disorders Center and the Children's Hospital of Philadelphia. The primary outcome was parental distress associated with information regarding long-term limitations. RESULTS: Approximately 46% of parents found information regarding future limitations to be extremely or very upsetting. In multivariate analysis, parents were more likely to consider information regarding future limitations distressing if they also found prognostic information upsetting (odds ratio [OR], 5.36; P<.001), struggled to accept their child's illness (OR, 2.57; P<.001), or had depression (OR, 1.79; P=.01). However, approximately 92% of parents considered information regarding potential future limitations to be extremely/very important. Those who found information regarding future limitations distressing were more likely to consider it important (96% vs 89%; P=.03) and to desire a precise understanding of their child's risks (92% vs 80%; P=.001). CONCLUSIONS: Although information regarding future limitations caused by cancer treatment is upsetting to many parents, the majority of them desire this information, and those who are distressed are more likely to value this information.

Cancer drug shortages: Awareness and perspectives from a representative sample of the US population.

BACKGROUND: Although cancer drug shortages are a persistent problem in oncology, little is known about the awareness and perspectives of the US population with respect to shortages. METHODS: In 2016, we administered a 13-item cross-sectional survey to 420 respondents who were randomly selected from an online, probability-based sample demographically representative of the adult US population with respect to sex, age, race/ethnicity, education, geography, and income. Analyses applied poststratification sampling weights to draw national inferences. RESULTS: Overall, 16% of respondents reported being aware of drug shortages. Those with a personal history of cancer were more likely to be aware (31% vs 14% [P = .03]). In the overall cohort, most reported wanting to be informed about a substitution due to shortage: 87% and 82% for major or minor differences in efficacy, and 87% and 83% for major or minor differences in side effects. Most also reported they would transfer care to avoid a substitution: 72% for major differences in efficacy, and 61% for major differences in side effects. Black respondents, the uninsured, the unemployed, those with lower income, and the less well-educated were all less likely to report that they would transfer care to avoid major differences in efficacy (all P < .05). CONCLUSION: These data suggest that the US population is largely unaware of cancer drug shortages. Moreover, if being treated for cancer, most people would want to know about drug substitutions, even if it were to result in only minor differences in efficacy or side effects. With more significant differences, many would transfer care. Cancer 2018;124:2205-11. © 2018 American Cancer Society.

Patient-reported outcomes enhance the survival prediction of traditional disease risk classifications: An international study in patients with myelodysplastic syndromes.

BACKGROUND: Current prognostic systems for myelodysplastic syndromes (MDS) are based on clinical, pathologic, and laboratory indicators. The objective of the current study was to develop a new patient-centered prognostic index for patients with advanced MDS by including self-reported fatigue severity into a well-established clinical risk classification: the International Prognostic Scoring System (IPSS). METHODS: A total of 469 patients with advanced (ie, IPSS intermediate-2 or high-risk) MDS were analyzed. Untreated patients (280 patients) were recruited into an international prospective cohort observational study to create the index. The index then was applied to an independent cohort including pretreated patients with MDS from the Dana-Farber Cancer Institute in Boston, Massachusetts (189 patients). At baseline, patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). RESULTS: A new prognostic index was developed: the FA-IPSS(h), in which FA stands for fatigue and h for higher-risk. This new risk classification enabled the authors to distinguish 3 subgroups of patients with distinct survival outcomes (ie, risk-1, risk-2, and risk-3). Patients classified as FA-IPSS(h) risk-1 had a median overall survival (OS) of 23 months (95% confidence interval [95% CI], 19-29 months), whereas those with risk-2 had a median OS of 16 months (95% CI, 12-17 months) and those with risk-3 had a median OS of 10 months (95% CI, 4-13 months). The predictive accuracy of this new index was higher than that of the IPSS alone in both the development cohort as well as in the independent cohort including pretreated patients. CONCLUSIONS: The FA-IPSS(h) is a novel patient-centered prognostic index that includes patients' self-reported fatigue severity. The authors believe its use might enhance physicians' ability to predict survival more accurately in patients with advanced MDS. Cancer 2018;124:1251-9. © 2017 American Cancer Society.

Estrogen-receptor status and risk of contralateral breast cancer following DCIS.

PURPOSE: As local therapies improve, contralateral breast cancer (CBC) risk for women with ductal carcinoma in situ (DCIS) may exceed the risk of a second ipsilateral breast cancer. We sought to determine whether estrogen-receptor (ER) status influenced CBC risk. METHODS: We identified women aged 40-79 with DCIS diagnosed between 1990 and 2002 using the Surveillance, Epidemiology, and End Results database. We used multivariable competing risk regression to examine predictors of time from index DCIS to CBC (invasive or in situ). RESULTS: Multivariable competing risk regression found ER status to be a highly significant predictor of CBC. The 10-year cumulative incidence was estimated to be 5.3% (95% CI 4.8-5.8%) among ER positive (ER+) cases and 3.3% (95% CI 2.6-4.0%) among ER negative (ER-). CONCLUSIONS: This finding suggests that ER+ DCIS may represent a field effect that confers increased propensity for developing cancer across breast tissue, regardless of laterality. In contrast, ER- DCIS may represent an isolated local event. Given that the majority of DCIS is ER+, and only a minority of DCIS patients receive hormonal therapy, consideration of ER status may influence treatment and surveillance approaches.

Meaningful changes in end-of-life care among patients with myeloma.

Patients with advanced myeloma experience a high symptom burden particularly near the end of life, making timely hospice use crucial. Little is known about the quality and determinants of end-of-life care for this population, including whether potential increases in hospice use are also accompanied by "late" enrollment (≤ 3 days before death). Using the Surveillance, Epidemiology, and End-Results-Medicare database, we identified patients ≥ 65 years diagnosed with myeloma between 2000 and 2013 who died by December 31, 2013. We assessed prevalence and trends in hospice use, including late enrollment. We also examined six established measures of potentially aggressive medical care at the end of life. Independent predictors of late hospice enrollment and aggressive end-of-life care were assessed using multivariable logistic regression analyses. Of 12,686 myeloma decedents, 48.2% enrolled in hospice. Among the 6111 who enrolled, 17.2% spent ≤ 3 days there. There was a significant trend in increasing hospice use, from 28.5% in 2000 to 56.5% by 2013 (Ptrend <0.001), no significant rise in late enrollment (12.2% in 2000 to 16.3% in 2013, Ptrend =0.19), and a slight decrease in aggressive end-of-life care (59.2% in 2000 to 56.7% in 2013, Ptrend =0.01). Patients who were transfusion-dependent, on dialysis, or survived for less than one year were more likely to enroll late in hospice and experience aggressive medical care at the end of life. Gains in hospice use for myeloma decedents were not accompanied by increases in late enrollment or aggressive medical care. These findings suggest meaningful improvements in end-of-life care for this population.

A flexible and coherent test/estimation procedure based on restricted mean survival times for censored time-to-event data in randomized clinical trials.

In randomized clinical trials where time-to-event is the primary outcome, almost routinely, the logrank test is prespecified as the primary test and the hazard ratio is used to quantify treatment effect. If the ratio of 2 hazard functions is not constant, the logrank test is not optimal and the interpretation of hazard ratio is not obvious. When such a nonproportional hazards case is expected at the design stage, the conventional practice is to prespecify another member of weighted logrank tests, eg, Peto-Prentice-Wilcoxon test. Alternatively, one may specify a robust test as the primary test, which can capture various patterns of difference between 2 event time distributions. However, most of those tests do not have companion procedures to quantify the treatment difference, and investigators have fallen back on reporting treatment effect estimates not associated with the primary test. Such incoherence in the "test/estimation" procedure may potentially mislead clinicians/patients who have to balance risk-benefit for treatment decision. To address this, we propose a flexible and coherent test/estimation procedure based on restricted mean survival time, where the truncation time τ is selected data dependently. The proposed procedure is composed of a prespecified test and an estimation of corresponding robust and interpretable quantitative treatment effect. The utility of the new procedure is demonstrated by numerical studies based on 2 randomized cancer clinical trials; the test is dramatically more powerful than the logrank, Wilcoxon tests, and the restricted mean survival time-based test with a fixed τ, for the patterns of difference seen in these cancer clinical trials.

Impact of lenalidomide use among non-transfusion dependent patients with myelodysplastic syndromes.

Chemotherapies approved for defined subgroups promise personalized oncologic care, but their off-label impact is unclear. Lenalidomide is approved for lower-risk, transfusion-dependent (TD) myelodysplastic syndromes (MDS) with del(5q), but frequently used in MDS outside this indication. We characterized lenalidomide use and outcomes among non-TD patients with MDS. Patients 65 or older diagnosed with MDS between 2007 and 2013 were identified using SEER; linked Medicare claims were evaluated for transfusions, lenalidomide use, and incident toxicities. TD was ≥2 transfusion episodes within an 8-week period; responses were transfusion independence (TI) and ≥50% transfusion reduction (minor response). We compared overall survival for non-TD patients receiving lenalidomide versus those not receiving lenalidomide, matched on disease and patient characteristics. We identified 676 patients who had received lenalidomide, including 275 (40.7%) TD and 401 (59.3%) non-TD; 18.5% (125/676) had zero claims for RBC transfusion prior to receiving lenalidomide. Incident toxicities among patients prescribed lenalidomide were similar in TD and non-TD groups, except incident thromboembolic events were higher among non-TD patients (10.8% vs. 6.0%, P = .04). Comparing 191 non-TD patients receiving lenalidomide within 6 months of MDS diagnosis to risk-matched MDS controls, lenalidomide was not associated with improved OS (P = .78). Among TD patients (n = 275), 31% achieved TI, and 30% achieved minor hematologic response, with a median time to TI of 4.1 weeks. In conclusion, we confirmed the benefit of lenalidomide among TD patients with MDS; however, many non-TD patients also received lenalidomide. These patients experienced accompanying toxicity without evidence of benefit in terms of transfusion needs or overall survival.

Parent understanding of the risk of future limitations secondary to pediatric cancer treatment.

BACKGROUND: Parents and physicians may have different understandings of a child's risk of future limitations due to cancer or cancer treatment. We evaluated alignment between parent- and physician-estimated risk of late effects. METHODS: We surveyed 352 parents of children with cancer within 12 weeks of diagnosis, and the children's oncologists, at Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Children's Hospital of Philadelphia. We assessed parent and physician estimations of the child's risk of future limitations in physical abilities, intelligence, or quality of life (QOL) due to cancer treatment. Physician-estimated risk of limitations ≥50% was considered high risk. RESULTS: Physicians considered 22% of children at high risk of physical impairments, 9% at high risk for impaired intelligence, and 6% at high risk for impaired QOL. Among high-risk children, 38% of parents recognized this risk in physical abilities, 21% in intelligence, and 5% in QOL. In multivariable analysis, parental understanding of risk, defined as concordant parent and physician estimates, was greater among parents of children at lower risk of future limitations (odds ratio 2.59; 95% confidence interval 1.35-4.96). Regardless of risk, 92% of parents considered it very/extremely important to receive information about potential health implications of cancer treatment. CONCLUSIONS: Although most parents want information about life after cancer, most parents of children at high risk of future impairment do not recognize this risk. Strategies to improve communication about late effects throughout pediatric cancer treatment should prioritize meeting information needs and improving parent understanding of the risk of impairment.

Disparities in prognosis communication among parents of children with cancer: The impact of race and ethnicity.

BACKGROUND: Most parents of children with cancer say they want detailed information about their child's prognosis. However, prior work has been conducted in populations of limited diversity. The authors sought to evaluate the impact of parental race/ethnicity on prognosis communication experiences among parents of children with cancer. METHODS: In total, 357 parents of children with cancer and the children's physicians were surveyed at Dana-Farber Cancer Institute/Boston Children's Hospital and Children's Hospital of Philadelphia. Outcome measures were parental preferences for prognostic information, physician beliefs about parental preferences, prognosis communication processes, and communication outcomes. Associations were assessed by logistic regression with generalized estimating equations to correct for physician clustering. RESULTS: Two hundred eighty-one parents (79%) were white, 23 (6%) were black, 29 (8%) were Hispanic, and 24 (7%) were Asian/other. Eighty-seven percent of parents wanted as much detail as possible about their child's prognosis, with no significant differences by race/ethnicity (P = .75). However, physician beliefs about parental preferences for prognosis communication varied based on parent race/ethnicity, with physicians considering black and Hispanic parents less interested in details about prognosis than whites (P = .003). Accurate understanding of a less favorable prognosis was greater among white (49%) versus nonwhite parents (range, 20%-29%), although this difference was not statistically significant (P = .14). CONCLUSIONS: Most parents, regardless of racial and ethnic background, want detailed prognostic information about their child's cancer. However, physicians underestimate the information needs of black and Hispanic parents. To meet parents' information needs, physicians should ask about parents' information preferences before prognosis discussions. Cancer 2017;123:3995-4003. © 2017 American Cancer Society.