The cost of delivering high-quality healthcare in America now consumes 17.7% of the nation’s gross domestic product according to Centers for Medicare & Medicaid Services National Health Expenditure Data. With costs threatening to disrupt accessible and equitable care for patients, policymakers are reassessing all matters and functions of the healthcare system to excise waste, redundancies, and costly services. To explore this subjects’ impact on oncology, NCCN hosted the NCCN Policy Summit: Innovative Solutions to Drive Down Healthcare Costs: Implications for Access to High Quality Cancer Care. This virtual summit featured multidisciplinary panel discussions and keynote addresses. Seeking to address barriers to low-cost, high-quality cancer care, panelists and keynotes presented innovative policy solutions to sustain high-quality oncologic care at lower costs to the health system. This article encapsulates the discussions held during the summit and expounds upon salient points where appropriate.
Terrell Johnson, Michelle McMurry-Heath, Ted Okon, David Rubin, and Robert W. Carlson
Rofieda R. Alwaqfi, Megan I. Samuelson, Natalya N. Guseva, Michelle Ouyang, Aaron D. Bossler, and Deqin Ma
Recurrent GLI1 gene fusions have been recently described in a subset of soft tissue tumors showing a distinct monotonous epithelioid morphology with a rich capillary network and frequent S100 protein expression. Three different fusion partners—ACTB, MALAT1, and PTCH1—have been reported with the PTCH1-GLI1 fusion from 2 patients only, both with head and neck tumors. Herein, we report for the first time a PTCH1-GLI1 fusion in a primary ovarian tumor from a female patient aged 54 years who presented with a 21-cm right ovarian mass and mesenteric metastasis. The tumor was diagnosed as “favor malignant melanoma” based on histologic examination and extensive immunohistochemistry studies. The patient received 4 cycles of pembrolizumab and 2 cycles of trabectedin but developed multiple metastases. A next-generation sequencing-based assay detected a PTCH1-GLI1 fusion, which led to a revised pathologic diagnosis and a change of the patient’s management. The patient was switched to the tyrosine kinase inhibitor (TKI) pazopanib to target the sonic hedgehog pathway. Her disease was stable 49 months post TKI therapy. Our case report is the first to show that a tumor with GLI1 oncogenic activation was sensitive to a TKI. The morphologic and immunohistochemistry similarities of our patient’s tumor to other recently described tumors harboring GLI1 fusions suggest that these tumors may all belong to the same entity of GLI1 fusion–positive neoplasms and may be treated similarly.
Yu Tian, Elham Kharazmi, Hermann Brenner, Xing Xu, Kristina Sundquist, Jan Sundquist, and Mahdi Fallah
Background: The aim of this study was to explore the risk of invasive colorectal cancer (CRC) in relatives of patients with colorectal carcinoma in situ (CCIS), which is lacking in the literature. Patients and Methods: We collected data from Swedish family-cancer datasets and calculated standardized incidence ratio (SIR) and cumulative risk of CRC in family histories of CCIS in first- and second-degree relatives. Family history was defined as a dynamic (time-dependent) variable allowing for changes during the follow-up period from 1958 to 2015. Of 12,829,251 individuals with available genealogical data, 173,796 were diagnosed with CRC and 40,558 with CCIS. Results: The lifetime (0–79 years) cumulative risk of CRC in first-degree relatives of patients with CCIS was 6.5%, which represents a 1.6-fold (95% CI, 1.5–1.7; n=752) increased risk. A similarly increased lifetime cumulative risk (6.7%) was found among first-degree relatives of patients with CRC (SIR, 1.6; 95% CI, 1.6–1.7; n=6,965). An increased risk of CRC was also found in half-siblings of patients with CCIS (SIR, 1.9; 95% CI, 1.1–3.0; n=18) and also in half-siblings of patients with CRC (SIR, 1.7; 95% CI, 1.3–2.1; n=78). Moreover, the increased risk of CRC was higher for younger age at diagnosis of CCIS in the affected first-degree relative and for younger age at diagnosis of CRC in the index person. Conclusions: Results of this study show that first-degree relatives and half-siblings of patients with CCIS have an increased risk of CRC, which is comparable in magnitude to the risk of those with a family history of invasive CRC. These findings extend available evidence on familial risk of CRC and may help to refine guidelines and recommendations for CRC screening.
Camilla Zimmermann, Ashley Pope, Breffni Hannon, Monika K. Krzyzanowska, Gary Rodin, Madeline Li, Doris Howell, Jennifer J. Knox, Natasha B. Leighl, Srikala Sridhar, Amit M. Oza, Rebecca Prince, Stephanie Lheureux, Aaron R. Hansen, Anne Rydall, Brittany Chow, Leonie Herx, Christopher M. Booth, Deborah Dudgeon, Neesha Dhani, Geoffrey Liu, Philippe L. Bedard, Jean Mathews, Nadia Swami, and Lisa W. Le
Background: Routine early palliative care (EPC) improves quality of life (QoL) for patients with advanced cancer, but it may not be necessary for all patients. We assessed the feasibility of Symptom screening with Targeted Early Palliative care (STEP) in a phase II trial. Methods: Patients with advanced cancer were recruited from medical oncology clinics. Symptoms were screened at each visit using the Edmonton Symptom Assessment System-revised (ESAS-r); moderate to severe scores (screen-positive) triggered an email to a palliative care nurse, who called the patient and offered EPC. Patient-reported outcomes of QoL, depression, symptom control, and satisfaction with care were measured at baseline and at 2, 4, and 6 months. The primary aim was to determine feasibility, according to predefined criteria. Secondary aims were to assess whether STEP identified patients with worse patient-reported outcomes and whether screen-positive patients who accepted and received EPC had better outcomes over time than those who did not receive EPC. Results: In total, 116 patients were enrolled, of which 89 (77%) completed screening for ≥70% of visits. Of the 70 screen-positive patients, 39 (56%) received EPC during the 6-month study and 4 (6%) received EPC after the study end. Measure completion was 76% at 2 months, 68% at 4 months, and 63% at 6 months. Among screen-negative patients, QoL, depression, and symptom control were substantially better than for screen-positive patients at baseline (all P<.0001) and remained stable over time. Among screen-positive patients, mood and symptom control improved over time for those who accepted and received EPC and worsened for those who did not receive EPC (P<.01 for trend over time), with no difference in QoL or satisfaction with care. Conclusions: STEP is feasible in ambulatory patients with advanced cancer and distinguishes between patients who remain stable without EPC and those who benefit from targeted EPC. Acceptance of the triggered EPC visit should be encouraged.
ClinicalTrials.gov identifier: NCT04044040.
Chetna Malhotra, Rahul Malhotra, Filipinas Bundoc, Irene Teo, Semra Ozdemir, Noreen Chan, and Eric Finkelstein
Background: Reducing suffering at the end of life is important. Doing so requires a comprehensive understanding of the course of suffering for patients with cancer during their last year of life. This study describes trajectories of psychological, spiritual, physical, and functional suffering in the last year of life among patients with a solid metastatic cancer. Patients and Methods: We conducted a prospective cohort study of 600 patients with a solid metastatic cancer between July 2016 and December 2019 in Singapore. We assessed patients’ psychological, spiritual, physical, and functional suffering every 3 months until death. Data from the last year of life of 345 decedents were analyzed. We used group-based multitrajectory modeling to delineate trajectories of suffering during the last year of a patient’s life. Results: We identified 5 trajectories representing suffering: (1) persistently low (47% of the sample); (2) slowly increasing (14%); (3) predominantly spiritual (21%); (4) rapidly increasing (12%); and (5) persistently high (6%). Compared with patients with primary or less education, those with secondary (high school) (odds ratio [OR], 3.49; 95% CI, 1.05–11.59) education were more likely to have rapidly increasing versus persistently low suffering. In multivariable models adjusting for potential confounders, compared with patients with persistently low suffering, those with rapidly increasing suffering had more hospital admissions (β=0.24; 95% CI, 0.00–0.47) and hospital days (β=0.40; 95% CI, 0.04–0.75) during the last year of life. Those with persistently high suffering had more hospital days (β=0.70; 95% CI, 0.23–1.17). Conclusions: The course of suffering during the last year of life among patients with cancer is variable and related to patients’ hospitalizations. Understanding this variation can facilitate clinical decisions to minimize suffering and reduce healthcare costs at the end of life.
Brooke E. Wilson, Michelle B. Nadler, Alexandra Desnoyers, and Eitan Amir
Background: Censoring due to early drug discontinuation (EDD) or withdrawal of consent or loss to follow-up (WCLFU) can result in postrandomization bias. In oncology, censoring rules vary with no defined standards. In this study, we sought to describe the planned handling and transparency of censoring data in oncology trials supporting FDA approval and to compare EDD and WCLFU in experimental and control arms. Methods: We searched FDA archives to identify solid tumor drug approvals and their associated trials between 2015 and 2019, and extracted the planned handling and reporting of censored data. We compared the proportion of WCLFU and EDD between the experimental and control arms by using generalized estimating equations, and performed logistic regression to identify trial characteristics associated with WCLFU occurring more frequently in the control group. Results: Censoring rules were defined adequately in 48 (59%) of 81 included studies. Only 14 (17%) reported proportions of censored participants clearly. The proportion of WCLFU was higher in the control group than in the experimental group (mean, 3.9% vs 2.5%; β-coefficient, −2.2; 95% CI, −3.1 to −1.3; P<.001). EDD was numerically higher in the experimental arm in 61% of studies, but there was no statistically significant difference in the proportion of EDD between the experimental and control groups (mean, 21.6% vs 19.9%, respectively; β-coefficient, 0.27; 95% CI, −0.32 to 0.87; P=.37). The proportion of EDD due to adverse effects (AEs) was higher in the experimental group (mean, 13.2% vs 8.5%; β-coefficient, 1.5; 95% CI, 0.57–2.45; P=.002). WCLFU was higher in the control group in studies with an active control group (odds ratio [OR], 10.1; P<.001) and in open label studies (OR, 3.00; P=.08). Conclusions: There are significant differences in WCLFU and EDD for AEs between the experimental and control arms in oncology trials. This may introduce postrandomization bias. Trials should improve the reporting and handling of censored data so that clinicians and patients are fully informed regarding the expected benefits of a treatment.