Local Ablative Therapy Associated with Immunotherapy in Locally Advanced Pancreatic Cancer: A Solution to Overcome the Double Trouble?—A Comprehensive Review

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains a major killer and is a challenging clinical research issue with abysmal survival due to unsatisfactory therapeutic efficacy. Two major issues thwart the treatment of locally advanced nonresectable pancreatic cancer (LAPC): high micrometastasis rate and surgical inaccessibility. Local ablative therapies induce a systemic antitumor response (i.e., abscopal effect) in addition to local effects. Thus, the incorporation of additional therapies could be key to improving immunotherapy’s clinical efficacy. In this systematic review, we explore recent applications of local ablative therapies combined with immunotherapy to overcome immune resistance in PDAC and discuss future perspectives and challenges. Particularly, we describe four chemoradiation studies and nine reports on irreversible electroporation (IRE). Clinically, IRE is the ablative therapy of choice, utilized in all but two clinical trials, and may create a favorable microenvironment for immunotherapy. Various immunotherapies have been used in combination with IRE, such as NK cell- or γδ T cell-based therapy, as well as immune checkpoint inhibitors. The results of the clinical trials presented in this review and the advancement potential of these therapies to phase II/III trials remain unknown. A multiple treatment approach involving chemotherapy, local ablation, and immunotherapy holds promise in overcoming the double trouble of LAPC.

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Cancer Statistics, 2021

Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2021)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.

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The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration

Alessandro Liberati, Douglas G. Altman, Jennifer Tetzlaff … (2010)

Systematic reviews and meta-analyses are essential to summarise evidence relating to efficacy and safety of healthcare interventions accurately and reliably. The clarity and transparency of these reports, however, are not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (quality of reporting of meta-analysis) statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realising these issues, an international group that included experienced authors and methodologists developed PRISMA (preferred reporting items for systematic reviews and meta-analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this explanation and elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA statement, this document, and the associated website (www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.

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Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer

Hossein Borghaei, Luis Paz-Ares, Leora Horn … (2015)

Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity.