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BACKGROUND: There is a lack of predictive markers informing on the risk of colitis in patients treated with immune checkpoint inhibitors (ICIs). The aim of this study was to identify potential factors associated with development of ICI colitis. METHODS: We performed a retrospective analysis of melanoma patients at Dana-Farber Cancer Institute who received PD-1, CTLA-4, or combination ICIs between May 2011 to October 2017. Clinical and laboratory characteristics associated with pathologically confirmed ICI colitis were evaluated using multivariable logistic regression analyses. External confirmation was performed on an independent cohort from Massachusetts General Hospital. RESULTS: The discovery cohort included 213 patients of whom 37 developed ICI colitis (17%). Vitamin D use was recorded in 66/213 patients (31%) before starting ICIs. In multivariable regression analysis, vitamin D use conferred significantly reduced odds of developing ICI colitis (OR 0.35, 95% CI 0.1-0.9). These results were also demonstrated in the confirmatory cohort (OR 0.46, 95% CI 0.2-0.9) of 169 patients of whom 49 developed ICI colitis (29%). Pre-treatment neutrophil-to-lymphocyte ratio (NLR) ≥5 predicted reduced odds of colitis (OR 0.34, 95% CI 0.1-0.9) only in the discovery cohort. CONCLUSIONS: This is the first study to report that among patients treated with ICIs, vitamin D intake is associated with reduced risk for ICI colitis. This finding is consistent with prior reports of prophylactic use of vitamin D in ulcerative colitis and graft-versus-host-disease. This observation should be validated prospectively in future studies.
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Antígeno CTLA-4/genética , Colitis/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/genética , Vitamina D/administración & dosificación , Anciano , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Colitis/inducido químicamente , Colitis/patología , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Linfocitos/efectos de los fármacos , Masculino , Melanoma/complicaciones , Melanoma/patología , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunologíaRESUMEN
PURPOSE: We conducted a systematic review to evaluate the outcome of patients with early-stage (stages I-III) mismatch repair deficient (dMMR) colorectal cancer (CRC) receiving neoadjuvant immunotherapy (NIT) with immune checkpoint inhibitor (ICI)-based regimens. METHODS: MEDLINE, Scopus, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were searched for publications reporting the outcome of patients with early-stage dMMR CRC receiving NIT. The primary outcome measures were the complete response (CR) rate (clinical CR [cCR] or pathologic CR [pCR]) and the incidence of grade 3 or higher toxicities. RESULTS: The search identified 37 publications that included 423 patients with colon (n = 326, 77%) and rectal (n = 97,23%) cancers aged 19-82 years; most patients had stage III CRC (88%). Approximately 67% of patients received monotherapy with anti-PD-1 agents; the rest received dual ICIs (ipilimumab plus nivolumab). The CR rate (pCR + cCR) in the overall population was 72% (305 of 423). The R0 resection and pCR rates were 99.3% and 70% among the patients undergoing surgery, respectively. Only four (0.9%) patients had primary resistance to NIT. After median follow-up periods ranging from 4 to 27 months, 3 (0.7%) patients progressed after an initial response. Grade 3 or higher toxicities were uncommon (6.3%), rarely delaying planned surgery. CONCLUSION: NIT in patients with early-stage dMMR CRC is associated with a high response rate, low primary resistance to immunotherapy and cancer recurrence rate, and an excellent safety profile. The findings of the present systematic review support further investigation of NIT in patients with early-stage dMMR CRC, with a particular emphasis on the organ-preserving potential of this strategy.
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Neoplasias Colorrectales , Reparación de la Incompatibilidad de ADN , Inmunoterapia , Terapia Neoadyuvante , Reparación de la Incompatibilidad de ADN/genética , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Inhibidores de Puntos de Control Inmunológico , Resultado del Tratamiento , Estadificación de NeoplasiasRESUMEN
The organ preservation strategy in non-metastatic rectal cancer is a rapidly evolving, novel treatment paradigm that is offered outside of a clinical trial in many advanced cancer centers. However, for non-metastatic colon cancer, upfront surgery followed by adjuvant chemotherapy in patients deemed at risk of cancer recurrence is the current standard of care. A significant proportion of patients with non-metastatic colon cancer harbor a deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) signature in tumors, which predicts a deep and durable response to immune checkpoint inhibitors (ICI) in a large proportion of such patients. This opens an opportunity for organ preservation in colon cancer in select circumstances. Herein, we describe a patient with locally advanced dMMR/MSI-H colon cancer who could not undergo standard colon surgery but achieved complete remission following treatment with ICI.
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Emerging retrospective and prospective studies indicate that immune checkpoint inhibitors (ICIs) can be safe and effective cancer treatments among people living with human immunodeficiency virus (PLWH), however this high-cancer-risk population has often been excluded from groundbreaking cancer ICI trials. Our study aimed to characterize the current rate of exclusion and conditional inclusion of PLWH in cancer ICI trials by tumor type, trial phase, and year. ClinicalTrials.gov cancer ICI trials with planned starts between 1/1/2019 and 10/20/2020 were identified. Based on trial eligibility criteria, trials were categorized as "excluded" if PLWH could not enroll, "conditionally included" if only PLWH with adequate immune function were allowed, or "included/not specified" if HIV was not mentioned in the eligibility criteria. Trials from 2014 were separately collected for comparison over time. The number of trials excluding PLWH were compared to the included/not specified group using Fisher's exact test. Of 809 trials analyzed from 2019 to 2020, 74.4% excluded, 6.9% conditionally included, and 18.7% included/did not specify PLWH. Early phase trials excluded PLWH more frequently than late phase trials. The 2019-2020 trial cohort showed no significant change in exclusion of PLWH compared to 2014. Despite increasing evidence for safe and effective ICI use for PLWH, most cancer ICI trials exclude PLWH and few studies permit PLWH to participate, even if HIV is well-controlled.
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Antineoplásicos/uso terapéutico , Infecciones por VIH/complicaciones , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Toma de Decisiones Clínicas , Ensayos Clínicos como Asunto , Manejo de la Enfermedad , Humanos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias/patologíaRESUMEN
This article was migrated. The article was marked as recommended. With nearly half the world's population using social media, platforms like Instagram, Twitter, and Facebook have become popular sources of information gathering and sharing for the general public. In medicine, social media is increasingly used to educate patients due its wide reach and interactive nature. Early studies showed that these social media-based initiatives can even promote behavioral change by increasing public knowledge and self-efficacy. Several barriers such as time and technical skills, however, prevent healthcare workers from using social media platforms to promote public health education. The following twelve tips may help reduce these barriers and create more opportunities for patients to easily access quality medical information on social media. Creating an effective public health education platform on social media involves identifying clear goals, understanding the social context of all messaging, recruiting a motivated team, creating a style guide, vetting content for accuracy, and interacting with social media followers. These tips will help build an accurate and quality social media public health education campaign.
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PROBLEM: On March 17, 2020, the Association of American Medical Colleges recommended the suspension of all direct patient contact responsibilities for medical students because of the COVID-19 pandemic. Given this change, medical students nationwide had to grapple with how and where they could fill the evolving needs of their schools' affiliated clinical sites, physicians, patients, and the community. APPROACH: At Harvard Medical School (HMS), student leaders created a COVID-19 Medical Student Response Team to: (1) develop a student-led organizational structure that would optimize students' ability to efficiently mobilize interested peers in the COVID-19 response, both clinically and in the community, in a strategic, safe, smart, and resource-conscious way; and (2) serve as a liaison with the administration and hospital leaders to identify evolving needs and rapidly engage students in those efforts. OUTCOMES: Within a week of its inception, the COVID-19 Medical Student Response Team had more than 500 medical student volunteers from HMS and had shared the organizational framework of the response team with multiple medical schools across the country. The HMS student volunteers joined any of the 4 virtual committees to complete this work: Education for the Medical Community, Education for the Broader Community, Activism for Clinical Support, and Community Activism. NEXT STEPS: The COVID-19 Medical Student Response Team helped to quickly mobilize hundreds of students and has been integrated into HMS's daily workflow. It may serve as a useful model for other schools and hospitals seeking medical student assistance during the COVID-19 pandemic. Next steps include expanding the initiative further, working with the leaders of response teams at other medical schools to coordinate efforts, and identifying new areas of need at local hospitals and within nearby communities that might benefit from medical student involvement as the pandemic evolves.