Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma.

BACKGROUND: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown. METHODS: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated. RESULTS: At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P = 0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group. CONCLUSIONS: Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.).

Evaluation of the Durability of the Immune Humoral Response to COVID-19 Vaccines in Patients With Cancer Undergoing Treatment or Who Received a Stem Cell Transplant.

Importance: The durability of the antibody response to COVID-19 vaccines in patients with cancer undergoing treatment or who received a stem cell transplant is unknown and may be associated with infection outcomes. Objective: To evaluate anti-SARS-CoV-2 spike protein receptor binding domain (anti-RBD) and neutralizing antibody (nAb) responses to COVID-19 vaccines longitudinally over 6 months in patients with cancer undergoing treatment or who received a stem cell transplant (SCT). Design, Setting, and Participants: In this prospective, observational, longitudinal cross-sectional study of 453 patients with cancer undergoing treatment or who received an SCT at the University of Kansas Cancer Center in Kansas City, blood samples were obtained before 433 patients received a messenger RNA (mRNA) vaccine (BNT162b2 or mRNA-1273), after the first dose of the mRNA vaccine, and 1 month, 3 months, and 6 months after the second dose. Blood samples were also obtained 2, 4, and 7 months after 17 patients received the JNJ-78436735 vaccine. For patients receiving a third dose of an mRNA vaccine, blood samples were obtained 30 days after the third dose. Interventions: Blood samples and BNT162b2, mRNA-1273, or JNJ-78436735 vaccines. Main Outcomes and Measures: Geometric mean titers (GMTs) of the anti-RBD; the ratio of GMTs for analysis of demographic, disease, and treatment variables; the percentage of neutralization of anti-RBD antibodies; and the correlation between anti-RBD and nAb responses to the COVID-19 vaccines. Results: This study enrolled 453 patients (mean [SD] age, 60.4 [13,1] years; 253 [56%] were female). Of 450 patients, 273 (61%) received the BNT162b2 vaccine (Pfizer), 160 (36%) received the mRNA-1273 vaccine (Moderna), and 17 (4%) received the JNJ-7846735 vaccine (Johnson & Johnson). The GMTs of the anti-RBD for all patients were 1.70 (95% CI, 1.04-2.85) before vaccination, 18.65 (95% CI, 10.19-34.11) after the first dose, 470.38 (95% CI, 322.07-686.99) at 1 month after the second dose, 425.80 (95% CI, 322.24-562.64) at 3 months after the second dose, 447.23 (95% CI, 258.53-773.66) at 6 months after the second dose, and 9224.85 (95% CI, 2423.92-35107.55) after the third dose. The rate of threshold neutralization (≥30%) was observed in 203 of 252 patients (80%) 1 month after the second dose and in 135 of 166 patients (81%) 3 months after the second dose. Anti-RBD and nAb were highly correlated (Spearman correlation coefficient, 0.93 [0.92-0.94]; P < .001). Three months after the second dose, anti-RBD titers were lower in male vs female patients (ratio of GMTs, 0.52 [95% CI, 0.34-0.81]), patients older than 65 years vs patients 50 years or younger (ratio of GMTs, 0.38 [95% CI, 0.25-0.57]), and patients with hematologic malignant tumors vs solid tumors (ratio of GMTs, 0.40 [95% CI, 0.20-0.81]). Conclusions and Relevance: In this cross-sectional study, after 2 doses of an mRNA vaccine, anti-RBD titers peaked at 1 month and remained stable over the next 6 months. Patients older than 65 years of age, male patients, and patients with a hematologic malignant tumor had low antibody titers. Compared with the primary vaccine course, a 20-fold increase in titers from a third dose suggests a brisk B-cell anamnestic response in patients with cancer.

Incidence of Intracranial Melanoma Progression in the Setting of Positive Extracranial Response to Targeted Therapy and Immunotherapy: An Indication for More Frequent Screening in This Population?

Background and objective The incidence of intracranial metastases from melanoma is on the rise. In this study, we aimed to determine the incidence of intracranial disease progression in patients on BRAF/MEK targeted therapy and immunotherapy in the setting of controlled or improving extracranial disease. Methods This was a single-center, retrospective review that involved patients who underwent stereotactic radiosurgery (SRS) for intracranial metastatic melanoma between January 1, 2014, and December 31, 2018. We focused on BRAF/MEK mutation status and dates of treatment with BRAF/MEK targeted therapy, immunotherapy [ipilimumab (Yervoy), nivolumab (Opdivo), or pembrolizumab (Keytruda)], and combination targeted and immunotherapy. Results A total of 51 patients were enrolled: 36 males and 15 females. The average age of the patients was 58.6 years, and 26 among them were BRAF mutation-positive. Seventeen had prior surgery with SRS as adjuvant therapy. The other 34 had SRS as primary treatment. Forty-two patients had extracranial disease present at the time of SRS. There were 34 patients treated with targeted and immune therapy. Overall, 16 patients (47.1%) demonstrated controlled or improving extracranial disease, and 18 (52.9%) demonstrated progressing extracranial disease at the time of SRS. In the subgroup analysis, patients treated with BRAF/MEK targeted therapy demonstrated a 75% rate of extracranial disease control. The extracranial disease was controlled in 43.75% of patients on immunotherapy with intracranial progression, while it was controlled in 30% of patients on both BRAF/MEK targeted therapy and immunotherapy with intracranial progression. Sixteen patients (47.1%) developed intracranial metastasis in our study while having a stable systemic disease with BRAF/MEK targeted therapy, immunotherapy, or a combination of the two. Conclusion Based on our findings, a systemic response to targeted therapy and immunotherapy does not necessarily parallel intracranial protection.

Economics of Using Telemedicine to Supplement Hospice Care in Rural Areas.

Background: Hospice care in rural areas is often characterized by provider shortages and vast geographical service areas to cover, making access to quality end-of-life care challenging. Telemedicine, broadly, is the utilization of interactive televideo (ITV) technology to provide health services over a distance. For over 25 years, telemedicine has been proposed as a solution to address access issues. In 2015, the University of Kansas Medical Center (Kansas City, Kansas) partnered with Hospice Services, Inc. (HSI) (Phillipsburg, Kansas), to augment traditional, face-to-face (FTF) hospice care with hospice care delivered through mobile tablets. Objective: This work examines the costs of TeleHospice (TH) (telemedicine use in hospice care) when compared with the costs of FTF hospice services. Design: Detailed administrative data from July 1, 2018, to December 31, 2018, were analyzed to estimate the costs of service after TH use was inculcated into routine practice. Results: his, which averages a daily census of 34 patients, conducted 257 calls, averaging 28 hours a month. The average time for a TH call was 18 and 17 minutes for nursing and medical director calls, respectively. Through various hospice functions, including administrative, patient, and nonpatient-related connections, HSI saved over $115,000 in staff travel time and mileage reimbursement. Administratively, by hosting their weekly 15-member interdisciplinary meeting through ITV, HSI saved $29,869 of staff travel time and mileage reimbursement. Conclusions: Our estimates indicate substantial cost saving potential with the use of TH services. Further research is needed to assess the effects of TH utilization on the experiences and subsequent cost of hospice care.

Continuous versus intermittent BRAF and MEK inhibition in patients with BRAF-mutated melanoma: a randomized phase 2 trial.

Preclinical modeling suggests that intermittent BRAF inhibitor therapy may delay acquired resistance when blocking oncogenic BRAFV600 in melanoma1,2. We conducted S1320, a randomized, open-label, phase 2 clinical trial (NCT02196181) evaluating whether intermittent dosing of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib improves progression-free survival in patients with metastatic and unresectable BRAFV600 melanoma. Patients were enrolled at 68 academic and community sites nationally. All patients received continuous dabrafenib and trametinib during an 8-week lead-in period, after which patients with non-progressing tumors were randomized to either continuous or intermittent dosing of both drugs on a 3-week-off, 5-week-on schedule. The trial has completed accrual and 206 patients with similar baseline characteristics were randomized 1:1 to the two study arms (105 to continuous dosing, 101 to intermittent dosing). Continuous dosing yielded a statistically significant improvement in post-randomization progression-free survival compared with intermittent dosing (median 9.0 months versus 5.5 months, P = 0.064, pre-specified two-sided α = 0.2). Therefore, contrary to the initial hypothesis, intermittent dosing did not improve progression-free survival in patients. There were no differences in the secondary outcomes, including overall survival and the overall incidence of treatment-associated toxicity, between the two groups.

TeleHospice: A Community-Engaged Model for Utilizing Mobile Tablets to Enhance Rural Hospice Care.

BACKGROUND: In rural communities, providing hospice care can be a challenge. Hospice personnel sometimes travel great distances to reach patients, resulting in difficulty maintaining access, quality, cost-effectiveness, and safety. In 1998, the University of Kansas Medical Center piloted the country's first TeleHospice (TH) service. At that time, challenges with broad adoption due to cost and attitudes regarding technology were noted. A second TH project was launched in early 2017 using newer technology; this article updates that ongoing implementation. METHODS: The Organizational Change Manager was followed for the guided selection of the hospice partner. The University of Kansas Medical Center partnered with Hospice Services, Inc. (HSI), a leader in rural hospice care, providing services to 16 Kansas counties. Along with mobile tablets, a secure cloud-based videoconferencing solution was chosen for ease of use. RESULTS: From August 2017 through January 2018, 218 TH videoconferencing encounters including 917 attendees occurred. Calls were made for direct patient care, family support, and administrative purposes. These TH calls have been shown to save HSI money, and initial reports suggest they may strengthen the communication and relationships between staff, patients, and the patient's family. CONCLUSION: Finding innovative, cost-effective, and community-driven approaches such as TH are needed to continually advance hospice care. TeleHospice's potential to supplement and improve hospice services while reducing costs is significant, but continued research is needed to understand best fit within frontier hospices, to inform future urban applications, and to address reimbursement.

Expanding Local Cancer Clinical Trial Options: Analysis of the Economic Impact of the Midwest Cancer Alliance in Kansas.

PURPOSE: Patients benefit from receiving cancer treatment closer to home when possible and at high-volume regional centers when specialized care is required. The purpose of this analysis was to estimate the economic impact of retaining more patients in-state for cancer clinical trials and care, which might offset some of the costs of establishing broader cancer trial and treatment networks. METHOD: Kansas Cancer Registry data were used to estimate the number of patients retained in-state for cancer care following the expansion of local cancer clinical trial options through the Midwest Cancer Alliance based at the University of Kansas Medical Center. The 2014 economic impact of this enhanced local clinical trial network was estimated in four parts: Medical spending was estimated on the basis of National Cancer Institute cost-of-care estimates. Household travel cost savings were estimated as the difference between in-state and out-of-state travel costs. Trial-related grant income was calculated from administrative records. Indirect and induced economic benefits to the state were estimated using an economic impact model. RESULTS: The authors estimated that the enhanced local cancer clinical trial network resulted in approximately $6.9 million in additional economic activity in the state in 2014, or $362,000 per patient retained in-state. This estimate includes $3.6 million in direct spending and $3.3 million in indirect economic activity. The enhanced trial network also resulted in 45 additional jobs. CONCLUSIONS: Retaining patients in-state for cancer care and clinical trial participation allows patients to remain closer to home for care and enhances the state economy.

A Collaborative Step-Wise Process to Implementing an Innovative Clinic for Adult Survivors of Childhood Cancer.

With a 5 year survival rate of approximately 80%, there is an increasing number of childhood cancer survivors in the United States. Childhood cancer survivors are at an increased risk for physical and psychosocial health problems many years after treatment. Long-term follow-up care should include education, development of individualized follow up plans and screening for health problems in accordance with the Children's Oncology Group survivor guidelines. Due to survivor, provider and healthcare system related barriers, adult survivors of childhood cancer (ASCC) infrequently are receiving care in accordance to these guidelines. In this paper we describe the stepwise process and collaboration between a children's hospital and an adult academic medical center that was implemented to develop the Survivorship Transition Clinic and address the needs of ASCC in our region. In the clinic model that we designed ASCC follow-up with a primary care physician in the adult setting who is knowledgeable about late effects of childhood cancer treatment and are provided transition support and education by a transition nurse navigator.

The decreasing cost of telemedicine and telehealth.

The teleoncology practice based at the University of Kansas Medical Center (KUMC) in Kansas City, Kansas, is one of the longest running practices of its kind worldwide. The practice began in 1995 and connected an oncologist at KUMC with a rural medical center in Hays, Kansas. Fifteen years later, the practice continues to thrive at Hays Medical Center and has also expanded to include two additional sites within the state-the Northeast Kansas Center for Health and Wellness in Horton and Goodland Regional Medical Center in Goodland-that offer regularly scheduled teleoncology clinics. While the KUMC practice has witnessed an expansion in service sites throughout its history, the practice has seen a significant decrease in the costs associated with providing such services since its inception. The cost decrease can, in part, be attributed to an increase in the number of teleoncology visits conducted through the practice since it began. In Fiscal Year 1995 (FY 1995), 103 teleoncology visits resulted in a cost per visit of $812. Five years later, the FY 2000 $410 per visit cost for 121 visits was almost half the cost identified in the initial cost analysis. The FY 2003 cost per visit for 219 visits saw another decrease to $401, and the most recent FY 2005 cost analysis yielded another decrease to $251 per visit for 235 visits. The data reported below are likely to be the best now available to track time trends in the cost of providing telemedicine or telehealth consultations. The Conclusion and Policy Recommendations at the end of this article will focus on both the cost-time profile and some other challenges and lessons learned.

Defining the needs of a telemedicine service.

While telemedicine programme objectives, technologies and even philosophies will differ, certain common factors that enhance programme success can be identified. For example, a programme design which is driven by technological imperatives is likely to fail. It must also be recognized that telemedicine programmes cannot force remote sites to use their services. Thus developers must assess the needs for the proposed telemedicine service from a clinical, economic and technical perspective. From a clinical perspective, it is important to remember that certain clinical services can be provided via telemedicine while others cannot. Programme developers must recognize the significant role of the remote team in sustaining services; the on-site presenter is essential for the successful practice of telemedicine. Evaluating a telemedicine programme should be viewed as an integral step in its design and implementation. One site may define effectiveness in terms of access to services while another may measure success by cost savings. The success of future telemedicine programmes will be strongly related to their ability to recognize that they should be used to enhance current health-care delivery rather than to replace it.

A Phase II trial of epothilone B analogue BMS-247550 (NSC #710428) ixabepilone, in patients with advanced pancreas cancer: a Southwest Oncology Group study.

PURPOSE: The purpose of this Phase II multi-institutional study was to define the efficacy and toxicity of ixabepilone in patients with advance pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients were required to have pancreatic adenocarcinoma and metastatic or recurrent disease that was not amenable to curative resection. Performance status was 0-1, and patients could not have had prior chemotherapy, or chemoradiation therapy for their advanced disease although prior local palliative radiation was allowed. Ixabepilone was administered iv as a 3 hour infusion every 21 days. Initially, the dose was 50 mg/m(2) but this was lowered to 40 mg/m(2) shortly after the trial opened because of concerns about neurotoxicity. RESULTS: Sixty-two patients were registered however 2 were ineligible because they did not have recurrent or metastatic disease. For the 60 eligible patients, 22 had performance status of 0 and 38 performance status of 1. The estimated 6-month survival was 60% (95% CI 48%-72%) with a median survival of 7.2 months and an estimated time to treatment failure of 2.3 months. Out of 56 patients with measurable disease there were 5 confirmed partial responses for a confirmed response probability of 9% (95% CI 3%-20%) and 7 unconfirmed partial responses for an overall response probability of 21% (95% CI 12%-34%). Common toxicities were neutropenia/granulocytopenia, nausea and vomiting and neuropathy. There was one death, cause not determined but judged "possibly" related to treatment. CONCLUSION: Ixabepilone shows encouraging activity in patients with advanced pancreatic cancer and should be investigated further in this disease.

Diffusion theory and telemedicine adoption by Kansas health-care providers: critical factors in telemedicine adoption for improved patient access.

Twenty counties in Kansas were randomly selected from those designated as rural on the basis of their populations. A sample of 356 physicians and physicians' assistants in these counties was chosen. A postal survey was sent to the identified providers up to three times. One hundred and eighty-six of the questionnaires were returned (a response rate of 52%). In all, 76% of the respondents were physicians, 76% were men and 42% were family practitioners. Practitioners were classified as adopters or non-adopters of telemedicine, based on their report of whether they had ever referred one or more patients for a health-care consultation via telemedicine. Of the 167 participants who marked this item, 30 (18%) were adopters and 137 (82%) were non-adopters. Among the adopters, 16 (53%) said that they expected to use telemedicine with about the same frequency or more often in the future. In contrast, 61 (45%) non-adopters reported that they did not expect to refer patients by telemedicine in the future and 51 (37%) were unsure. Neither age (r = 0.16, P = 0.44) nor gender (chi2 = 2.35, P = 0.13) was related to the adoption variable or the number of referrals made to telemedicine clinics. The results suggest that adopters and non-adopters of telemedicine perceive its value very differently, and that an opportunity exists to promote the concept to non-adopters more effectively.

Online cancer services: types of services offered and associated health outcomes.

There are advantages and disadvantages associated with utilization of online health services among individuals living with cancer. Accessing accurate, reliable health-related information online gives patients the power to enhance their understanding of information they obtain from their health care providers. However, online health information can often be confusing for patients to interpret, and it can sometimes be conflicting or incorrect. Based on a framework by Eysenbach, the following paper discusses various types of cancer services that are available online, and it addresses both positive and negative health outcomes that have been linked to utilizing such services.

An empirical chart analysis of the suitability of telemedicine for hospice visits.

Telehospice (TH) utilizes telemedicine technology to provide care at the end of life. A bistate project was launched in 1998 to study the use of home-based telemedicine for routine hospice care. Videophones were deployed for telenursing visits and evaluations by social workers. In order to determine what proportion of home hospice visits could be performed using currently available telemedicine technology, we reviewed clinical records retrospectively for hospice nurse home visits. Clinical notes documenting home nursing visits were obtained from two large hospices, one based in Kansas, and the other in Michigan. Records were randomly selected for patients who received hospice nurse visits during the month of January 2000. The charts were reviewed for patient demographic information, patient assessments, teaching activities, and interventions. Five hundred ninety-seven nursing notes were analyzed using an 85-item coding instrument. After careful review of the records, the coders also made a subjective observation regarding the suitability of each visit for telemedicine. As part of this analysis, we found that 64.5% of home hospice nursing visits could be performed by telemedicine. Using TH, it is possible to reduce the number of in-person visits, thereby significantly decreasing the cost of providing hospice care.

A cost analysis of a tele-oncology practice in the United States.

Oncology services have been provided by telemedicine from the University of Kansas Medical Center (KUMC) for almost 10 years. We have analysed the costs associated with providing tele-oncology clinics to a rural Kansas town for two fiscal years, 1995 and 2000. The aim was to compare recent tele-oncology costs with those of the first year of tele-oncology practice. A study conducted in 1995 showed that the average cost was $812 per telemedicine consultation. Data from fiscal year 2000 showed that the average cost was $410 per telemedicine consultation, a decrease of almost 50%. As the tele-oncology practice in Kansas continues to grow, it can be expected that the costs associated with providing tele-oncology services will continue to decline.

An estimation of costs of a pediatric telemedicine practice in public schools.

BACKGROUND: Costs per consult are a vital consideration in determining the viability of a telemedicine practice. This study estimated total, average, and marginal cost curves for an ambulatory pediatric telemedicine practice. OBJECTIVE: The objective of this study was to estimate the costs of providing 386 telemedicine clinical consults at school clinics during one school year (September, 1999 to May, 2000). Cost curves were used to estimate costs of clinics with varying numbers of consults. RESEARCH DESIGN: This analysis used cost data from school clinics and a university medical center, which provided physician inputs. Standard cost-accounting procedures were used. SUBJECTS: Cost analyses were conducted using 10 school clinics. Three hundred eighty-six consults were completed with 286 children. Seventy-one percent of the children were black or Hispanic. RESULTS: The average costs of a telemedicine consult ranged from a high of $7328.17 when only one consult was done to a low of $173.13 when 129 consults were completed. At 165 consults, extrapolations from the cost curves suggested that the average costs of a telemedicine consult and a medical center pediatric ambulatory consult were approximately equal, a little more than $153. At 200 consults, telemedicine was estimated to be equal to or less costly than conventional ambulatory care visits by some 9.5%. CONCLUSIONS: Point and CI estimates of average costs suggest that telemedicine is cost competitive with conventional clinics when 200 or more consults are provided. The limited evidence available suggests that telemedicine consults also may be quality competitive.