Potential application mechanism of traditional Chinese medicine in treating immune checkpoint inhibitor-induced colitis.

Cancer ranks among the foremost causes of mortality worldwide, posing a significant threat to human lives. The advent of tumor immunotherapy has substantially transformed the therapeutic landscape for numerous advanced malignancies, notably non-small cell lung cancer and melanoma. However, as immune checkpoint inhibitors (ICIs) are increasingly applied in clinical settings, a spectrum of undesired reactions, termed immune-related adverse events (irAEs), has emerged. These adverse reactions are associated with immunotherapy and can result in varying degrees of harm to the human body. Among these reactions, Immune checkpoint inhibitor-induced colitis (ICIIC) stands out as one of the most prevalent clinical adverse events. In contemporary times, traditional Chinese medicine (TCM) has demonstrated remarkable efficacy in addressing various maladies. Consequently, investigating the potential application and mechanisms of Chinese medicine in countering immune checkpoint inhibitor-induced colitis assumes significant importance in the treatment of this condition.

From immune checkpoints to therapies: understanding immune checkpoint regulation and the influence of natural products and traditional medicine on immune checkpoint and immunotherapy in lung cancer.

Lung cancer is a disease of global concern, and immunotherapy has brought lung cancer therapy to a new era. Besides promising effects in the clinical use of immune checkpoint inhibitors, immune-related adverse events (irAEs) and low response rates are problems unsolved. Natural products and traditional medicine with an immune-modulating nature have the property to influence immune checkpoint expression and can improve immunotherapy's effect with relatively low toxicity. This review summarizes currently approved immunotherapy and the current mechanisms known to regulate immune checkpoint expression in lung cancer. It lists natural products and traditional medicine capable of influencing immune checkpoints or synergizing with immunotherapy in lung cancer, exploring both their effects and underlying mechanisms. Future research on immune checkpoint modulation and immunotherapy combination applying natural products and traditional medicine will be based on a deeper understanding of their mechanisms regulating immune checkpoints. Continued exploration of natural products and traditional medicine holds the potential to enhance the efficacy and reduce the adverse reactions of immunotherapy.

Revolutionizing gastric cancer treatment: The potential of immunotherapy.

Gastric cancer, a prevalent malignancy worldwide, ranks sixth in terms of frequency and third in fatality, causing over a million new cases and 769000 annual deaths. Predominant in Eastern Europe and Eastern Asia, risk factors include family medical history, dietary habits, tobacco use, Helicobacter pylori, and Epstein-Barr virus infections. Unfortunately, gastric cancer is often diagnosed at an advanced stage, leading to a grim prognosis, with a 5-year overall survival rate below 5%. Surgical intervention, particularly with D2 Lymphadenectomy, is the mainstay for early-stage cases but offers limited success. For advanced cases, the National Comprehensive Cancer Network recommends chemotherapy, radiation, and targeted therapy. Emerging immunotherapy presents promise, especially for unresectable or metastatic cases, with strategies like immune checkpoint inhi-bitors, tumor vaccines, adoptive immunotherapy, and nonspecific immunomodulators. In this Editorial, with regards to the article "Advances and key focus areas in gastric cancer immunotherapy: A comprehensive scientometric and clinical trial review", we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

Risk Factors for Immune Checkpoint Inhibitor Immunotherapy Toxicity Among Older Adults with Cancer.

OBJECTIVES: Immune checkpoint inhibitor immunotherapy (IO) is revolutionizing cancer care but can lead to significant toxicity. This study seeks to describe potential risk factors for immune-related adverse events (irAEs) specifically among older adults. MATERIALS AND METHODS: This was a retrospective study at a single academic comprehensive cancer center based on chart review data abstracted by physicians. For patients aged ≥70 years, frequency, type, and grade of irAEs and their association with baseline patient demographics, comorbidities, mobility, and functional status were characterized using bivariate analysis. Based on those results, multivariable logistic regressions were constructed to model the association between these characteristics with any grade and grade 3 or higher irAEs. RESULTS: Data were analyzed for 238 patients aged ≥70 years who received IO for mostly (≥90%) advanced cancer between 2011 and 2018. Thirty-nine percent of older adults experienced an irAE and 13% experienced one that was grade 3 or higher. In the multivariable analysis, depression was associated with an increased incidence of any grade irAE, while decreased life-space mobility was associated with an increased incidence of grade ≥3 irAEs. CONCLUSION: Most characteristics of special interest among older adults, include fall risk, weight loss, cognitive limitations, and hearing loss, were not associated with irAEs in our study. However, decreased life-space mobility and depression are potential risk factors for IO toxicity among older adults with advanced cancer. Interventions designed to evaluate and mitigate modifiable risk factors for treatment-related toxicity are needed, and the results of this study may be useful for guiding those efforts.

Treatment-related adverse events of first-line immunotherapy versus sorafenib for advanced hepatocellular carcinoma: a meta-analysis.

BACKGROUND: Despite all the improvements achieved over the last decade, the use of immune checkpoint inhibitors (ICIs) has been associated to a wide range of adverse drug events, which are frequently markedly different from those observed with cytotoxic chemotherapy and targeted therapies, such as sorafenib. RESEARCH DESIGN AND METHODS: We performed a meta-analysis with the aim to compare grade 3/4 treatment-related adverse events (TRAEs), grade 5 TRAEs, serious TRAEs, and TRAEs leading to discontinuation in ICIs versus sorafenib across phase III clinical trials of first-line treatment for advanced hepatocellular carcinoma (HCC). RESULTS: Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Patients treated with ICIs showed higher risk of serious TRAEs (OR 1.48, 95% CI = 1.16-1.9) while sorafenib treatment was associated with higher risk of TRAEs leading to discontinuation (OR 0.65, 95% CI = 0.48-0.89). No differences in grade 3/4 TRAEs and grade 5 TRAEs. CONCLUSIONS: Beyond activity and efficacy, careful consideration should be given to toxicity while choosing the appropriate first-line treatment in HCC.

Hyperthermia combined with immune checkpoint inhibitor therapy: Synergistic sensitization and clinical outcomes.

BACKGROUND: Within the field of oncotherapy, research interest regarding immunotherapy has risen to the point that it is now seen as a key application. However, inherent disadvantages of immune checkpoint inhibitors (ICIs), such as their low response rates and immune-related adverse events (irAEs), currently restrict their clinical application. Were these disadvantages to be overcome, more patients could derive prolonged benefits from ICIs. At present, many basic experiments and clinical studies using hyperthermia combined with ICI treatment (HIT) have been performed and shown the potential to address the above challenges. Therefore, this review extensively summarizes the knowledge and progress of HIT for analysis and discusses the effect and feasibility. METHODS: In this review, we explored the PubMed and clinicaltrials.gov databases, with regard to the searching terms "immune checkpoint inhibitor, immunotherapy, hyperthermia, ablation, photothermal therapy". RESULTS: By reviewing the literature, we analyzed how hyperthermia influences tumor immunology and improves the efficacy of ICI. Hyperthermia can trigger a series of multifactorial molecular cascade reactions between tumors and immunization and can significantly induce cytological modifications within the tumor microenvironment (TME). The pharmacological potency of ICIs can be enhanced greatly through the immunomodulatory amelioration of immunosuppression, and the activation of immunostimulation. Emerging clinical trials outcome regarding HIT have verified and enriched the theoretical foundation of synergistic sensitization. CONCLUSION: HIT research is now starting to transition from preclinical studies to clinical investigations. Several HIT sensitization mechanisms have been reflected and demonstrated as significant survival benefits for patients through pioneering clinical trials. Further studies into the theoretical basis and practical standards of HIT, combined with larger-scale clinical studies involving more cancer types, will be necessary for the future.

The yin-yang of immunity: Immune dysregulation in myelodysplastic syndrome with different risk stratification.

Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid clonal diseases with diverse clinical courses, and immune dysregulation plays an important role in the pathogenesis of MDS. However, immune dysregulation is complex and heterogeneous in the development of MDS. Lower-risk MDS (LR-MDS) is mainly characterized by immune hyperfunction and increased apoptosis, and the immunosuppressive therapy shows a good response. Instead, higher-risk MDS (HR-MDS) is characterized by immune suppression and immune escape, and the immune activation therapy may improve the survival of HR-MDS. Furthermore, the immune dysregulation of some MDS changes dynamically which is characterized by the coexistence and mutual transformation of immune hyperfunction and immune suppression. Taken together, the authors think that the immune dysregulation in MDS with different risk stratification can be summarized by an advanced philosophical thought "Yin-Yang theory" in ancient China, meaning that the opposing forces may actually be interdependent and interconvertible. Clarifying the mechanism of immune dysregulation in MDS with different risk stratification can provide the new basis for diagnosis and clinical treatment. This review focuses on the manifestations and roles of immune dysregulation in the different risk MDS, and summarizes the latest progress of immunotherapy in MDS.

[Expertise for management of immune-related adverse events in cancer therapy: Mapping of French practicing]. / Gestion des toxicités induites par les inhibiteurs des points de contrôle immunitaire en oncologie : cartographie des pratiques françaises.

Immune checkpoint inhibitors (ICI) are an increasing proportion of oncology therapies. The oncologist is faced with the managing immune-mediated adverse effects (irAEs), which are sometimes complex, the introduction of ICIs in patients with history of autoimmune diseases, and rechallenging after toxicity. This multidisciplinary care is still uneven. The main objective of this study is to describe the management of this irAES within the university hospitals (UH) with oncology department and comprehensive cancer centers (CCC). We built this study around a survey sent to all UH and CCC in metropolitan France, as well as to all the hospitals authorized to treat cancer in the Nord Pas de Calais region, in order to assess the resources available and the areas of improvement. Multidisciplinary tumor boards dedicated to irAEs were available in 39% of CCCs and UHs, the remaining 61% had a network of specialists. The main problem encountered is the difficulty of bringing together the various specialists. The resources available at the regional level were not well known to the practitioners, who declared that the local resources were insufficient. We have identified five areas for improvement: the generalization of therapeutic education, the strengthening of the city-hospital link, the facilitation of access to specialists who know the specificities of irAE, the sharing of information through pharmacovigilance department and the promotion of further studies.

Systemic immunotherapy for the treatment of warts: A literature review.

BACKGROUND: Immunotherapy has emerged as a critical therapeutic tool for the treatment of warts. Immunotherapy for warts is currently restricted to recalcitrant lesions. A small number of regimens appear to be extremely effective. Furthermore, there is a scarcity of evidence-based research. OBJECTIVE: Furthermore, in the majority of cases, their safety and effectiveness have not been evaluated in double-blind, controlled clinical trials, making the reproducibility of many of the listed treatments difficult to analyze and a possible placebo effect difficult to rule out. METHODS: Analyzing and discussing different types of systemic immunotherapy. The different types of immunotherapy for warts are mentioned in this report. RESULTS: Systemic immunotherapeutic modalities commonly used in the treatment Echinacea, propolis, oral retinoids, glycyrrhizinic acid, levamisole, cimetidine, and zinc sulfate have all been reported as effective treatment modalities for different types of warts. CONCLUSION: Immunotherapy has emerged as one of the most important therapeutic modalities for warts. Such treatment is required not only for recalcitrant or multiple lesions, but also in the majority of treated cases.

Toxicity Profiles of Systemic Therapies for Advanced Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

Importance: The recent development of targeted therapy and immunotherapy has made neoadjuvant therapy an attractive option for patients with hepatocellular carcinoma (HCC). However, surgeons are concerned that adverse effects of neoadjuvant therapy with these agents could lead to delayed or even cancelled surgeries. Objective: To summarize the current evidence regarding toxicity profiles for tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) among patients with HCC. Data Sources: Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from January 1990 and December 2021. Study Selection: Single-group, placebo-controlled, and dual-agent clinical trials comparing TKIs and ICIs in patients with HCC were eligible for inclusion. Data Extraction and Synthesis: Following the Preferred Reporting Items in Systematic Reviews and Meta-analysis guideline, 2 reviewers independently extracted data. A random-effects model was used. Main Outcomes and Measures: The primary outcome was the proportion of patients with clinically significant liver-related adverse events. Secondary outcomes included the proportion of patients who experienced clinically relevant (grade 3 or higher) adverse events and significant adverse events (ie, those that were life threatening, required hospitalization, or prolonged disability) as well as the risk ratio (RR) of these complications. Results: Overall, 30 studies with 12 921 patients were included. Patients had a mean (range) age of 62 (18-89) years; a mean (SD) 84% (3) were male; a mean (SD) 82% (16) had Barcelona Clinic Liver Cancer stage C HCC; and a mean (SD) 97% (6) had Childs A cirrhosis. Overall, 21% (95% CI, 16%-26%) of patients receiving TKIs had liver toxic effects compared with 28% (95% CI, 21%-35%) of patients receiving ICIs. Severe adverse events occurred in 46% (95% CI, 40%-51%) of patients receiving TKIs compared with 24% (95% CI, 13%-35%) of patients receiving ICIs. Compared with patients receiving sorafenib, other TKIs were associated with similar rates of liver toxic effects (RR, 1.06; 95% CI, 0.92-1.24) but higher rates of severe adverse events (RR, 1.24; 95% CI, 1.07-1.44). Comparing ICIs with sorafenib, there were similar rates of liver toxic effects (RR, 1.10; 95% CI, 0.86-1.40) and severe adverse events (RR, 1.19; 95% CI, 0.95-1.50). Conclusions and Relevance: In this systematic review and meta-analysis, serious adverse events were lower with ICIs than with TKIs, while liver toxic effects were similar. Combination therapy with novel ICIs is an appealing option in trials of neoadjuvant therapy for patients with HCC, requiring evaluation in preoperative trials.

Inflammatory Burden and Immunomodulative Therapeutics of Cardiovascular Diseases.

Phenotyping cardiovascular illness and recognising heterogeneities within are pivotal in the contemporary era. Besides traditional risk factors, accumulated evidence suggested that a high inflammatory burden has emerged as a key characteristic modulating both the pathogenesis and progression of cardiovascular diseases, inclusive of atherosclerosis and myocardial infarction. To mechanistically elucidate the correlation, signalling pathways downstream to Toll-like receptors, nucleotide oligomerisation domain-like receptors, interleukins, tumour necrosis factor, and corresponding cytokines were raised as central mechanisms exerting the effect of inflammation. Other remarkable adjuvant factors include oxidative stress and secondary ferroptosis. These molecular discoveries have propelled pharmaceutical advancements. Statin was suggested to confer cardiovascular benefits not only by lowering cholesterol levels but also by attenuating inflammation. Colchicine was repurposed as an immunomodulator co-administered with coronary intervention. Novel interleukin-1ß and -6 antagonists exhibited promising cardiac benefits in the recent trials as well. Moreover, manipulation of gut microbiota and associated metabolites was addressed to antagonise inflammation-related cardiovascular pathophysiology. The gut-cardio-renal axis was therein established to explain the mutual interrelationship. As for future perspectives, artificial intelligence in conjunction with machine learning could better elucidate the sequencing of the microbiome and data mining. Comprehensively understanding the interplay between the gut microbiome and its cardiovascular impact will help identify future therapeutic targets, affording holistic care for patients with cardiovascular diseases.

A systematic review on the treatment of pediatric severe alopecia areata by topical immunotherapy or Anthralin (contact sensitization) or low-level light/laser therapy (LLLT): focus on efficacy, safety, treatment duration, recurrence, and follow-up based on clinical studies.

INTRODUCTION: Alopecia areata (AA) in its extensive and severe forms is treatment-challenging, especially in pediatrics. METHOD: A PRISMA-compliant systematic review of seven electronic databases was searched by the terms "alopecia areata," "pediatric," "topical immunotherapy," "Anthralin," and "light therapy" from inception until March 2021. All the alternative names of the disease and therapies have been included in the search terms. 790 articles went to title abstract review by two independent reviewers. In the subsequent level, a review of the full text of studies was conducted. RESULTS: Finally, 10 relevant articles in terms of content structure, subject coverage, and purpose, were selected for further review. The highest percentages of complete hair regrowth were 79.6% and 63.61% by SADBE (topical immunotherapy) and laser therapy. By Anthralin (contact sensitization), the complete response rate was below 50% (between 30 and 35%). Regarding average response, the most effective methods were local immunotherapy (with an average effectiveness of 53.8%), laser therapy (52.55%), and the use of Anthralin-induced contact dermatitis (30.86%), respectively. However, recurrence rate-after treatment with induced contact dermatitis by topical medications like Anthralin (contact sensitization)-was lower (mean 43.53%) in comparison with local immunotherapy (57%). In topical immunotherapy, light base therapy, and contact sensitization, the highest percentage of complete hair regrowth and the average response rate were (63.61% and 52.55%), (79.6% and 53.8%) and (32% and 30.8%), respectively. These methods are considered safe in children. CONCLUSION: A high and more than 50% efficacy in hair regrowth could be expected by topical immunotherapy and light/laser therapy method. No serious side effects have been observed by these methods that are well tolerated in children. Therefore, a combination of local immunotherapy and light/laser therapy could be suggested for the treatment of extensive AA in children. The use of Anthralin could be associated with a lower but more durable response. These points are important for patient selection in individualized situations.

Efficacy and Safety Associated With Immune Checkpoint Inhibitors in Unresectable Hepatocellular Carcinoma: A Meta-analysis.

Importance: Immune checkpoint inhibitors (ICIs) have yielded conflicting results in hepatocellular carcinoma (HCC). The overall effect of ICIs compared with standard therapies in unresectable HCC requires more research. Objective: To estimate the efficacy and safety associated with ICIs compared with standard therapies in patients with unresectable HCC. Data Sources: PubMed, Cochrane Library, Web of Science, Latin American and Caribbean Health Sciences Literature, and American Society of Clinical Oncology and European Society of Medical Oncology meeting proceedings were systematically searched. Reference lists from studies selected by electronic searching were manually searched to identify additional relevant studies. The search included literature published or presented from February 2010 to February 2020. Study Selection: From December 2019 to February 2020, independent reviewers evaluated each database, scanning the title, abstract, and keywords of every record retrieved. Full articles were further assessed if the information given suggested that the study was a randomized clinical trial (RCT) comparing ICIs vs standard therapies in the treatment of unresectable HCC. Data Extraction and Synthesis: The full text of the resulting studies and extracted data were reviewed independently according to PRISMA guidelines. Summary hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) were calculated by a random-effects model. The likelihood of ICIs being associated with overall response rate (ORR) and treatment-related adverse events (TRAEs) was expressed by odds ratios (ORs) using a random-effects model. Main Outcomes and Measures: The main outcomes were OS, PFS, ORR, and TRAEs. Results: Of 1836 studies yielded by the search, 3 were retained, totaling 1657 patients (985 treated with ICIs vs 672 receiving standard treatment). Two studies evaluated ICIs as monotherapy, and 1 study investigated the combination of ICIs with bevacizumab. Compared with standard therapies (sorafenib in first-line therapy or placebo in second-line therapy), ICIs were associated with significantly improved OS (HR, 0.75; 95% CI, 0.62-0.92; P = .006), PFS (HR, 0.74; 95% CI, 0.56-0.97; P = .03), and ORR (OR, 2.82; 95% CI 2.02-3.93; P < .001). The probability of grade 3 or 4 TRAEs was lower with ICIs than with sorafenib (OR, 0.44; 95% CI, 0.20-0.96; P = .04). Conclusions and Relevance: This meta-analysis found superior efficacy and safety associated with ICIs compared with standard therapies and highlights the survival benefit associated with the combination of antiangiogenic therapy with ICIs in first-line systemic therapy of unresectable HCC.

Inhibitors of immune checkpoints-PD-1, PD-L1, CTLA-4-new opportunities for cancer patients and a new challenge for internists and general practitioners.

The treatment of cancer patients with immune checkpoint inhibitors (ICI) (anti-CTLA-4, anti-PD-1, anti-PD-L1, combined therapy anti-PD-1/PD-L1 with anti-CTLA-4) has without doubt been a significant breakthrough in the field of oncology in recent years and constitutes a major step forward as a novel type of immunotherapy in the treatment of cancer. ICIs have contributed to a significant improvement in the outcome of treatment and prognosis of patients with different types of malignancy. With the expansion of the use of ICIs, it is expected that caregivers will face new challenges, namely, they will have to manage the adverse side effects associated with the use of these drugs. New treatment options pose new challenges not only for oncologists but also for specialists in other clinical fields, including general practitioners (GPs). They also endorse the need for taking a holistic approach to the patient, which is a principle widely recognized in oncology and especially relevant in the case of the expanding use of ICIs, which may give rise to a wide variety of organ complications resulting from treatment. Knowledge and awareness of the spectrum of immune-related adverse events (irAEs) will allow doctors to qualify patients for treatment more appropriately, prevent complications, correctly recognize, and ultimately treat them. Additionally, patients with more non-specific symptoms would be expected, in the first instance, to consult their general practitioners, as complications may appear even after the termination of treatment and do not always proceed in line with disease progression. Dealing with any iatrogenic complications, will not only be the remit of oncologists but because of the likelihood that specific organs may be affected, is likely to extend also to specialists in various fields of internal medicine. These specialists, e.g., endocrinologists, dermatologists, pulmonologists, and gastroenterologists, are likely to receive referrals for patients suffering from specific types of adverse events or will be asked to provide care in cases requiring hospitalization of patients with complications in their field of expertise. In view of these considerations, we believe that there is an urgent need for multidisciplinary teamwork in the treatment of cancer patients undergoing immunotherapy and suffering the consequent adverse reactions to treatment.

Biotin-induced thyroid stimulating hormone aberrations in the setting of immunotherapy.

INTRODUCTION: Immune checkpoint inhibitors are associated with immune-mediated thyroid disease and other endocrinopathies. Biotin is an over-the-counter supplement known to interfere with lab assays, including thyroid function tests. Biotin-induced complications with lab monitoring during immunotherapy have not been previously reported. CASE REPORT: We present a case of a 68-year old woman with hypothyroidism after initiating immune checkpoint blockade therapy and abnormal laboratory monitoring values while concurrently taking biotin supplements.Management & outcome: The patient was initiated on levothyroxine with subsequent dose increases over a period of weeks with resolution of symptoms and normalization of free thyroxine levels. Thyroid stimulating hormone (TSH) levels appeared to remain elevated until biotin supplements were held and levels normalized. DISCUSSION: The purpose of this report is to provide the first known incidence of biotin complicating the routine monitoring of immune checkpoint inhibitors with elevated TSH levels and to alert providers to elicit accurate medication histories regarding over-the-counter supplements.

Checkpoint blockade toxicities: Insights into autoimmunity and treatment.

Checkpoint blockade has transformed not only the way cancers are treated, but also highlighted the importance of mounting a proper immune response against tumors. Despite advances in the field of immunotherapy, many patients develop a range of inflammatory toxicities that limit the efficacy of these therapies. These toxicities range from barrier site injury, such as colitis, to endocrine organ dysfunction, such as diabetes. In order to properly treat patients with cancer and avoid checkpoint blockade induced toxicities, we must gain a deeper understanding of the underlying mechanisms generating these adverse events. Cytotoxic and tissue-resident T cells likely play an important role in mediating some toxicities, though high levels of cytokines and the generation of auto-antibodies in other toxicities demonstrates these mechanisms are not all shared. Certain risk factors for specific toxicities may be able to predict who might benefit most from alternative therapies given the risk-benefit associated with checkpoint blockade. As the targets of checkpoint inhibitors have important functions in the prevention of autoimmunity, insights into risk factors and causes of toxicities will further our knowledge of fundamental immunology and enable the development of novel therapeutics.

Combination of Ablation and Immunotherapy for Hepatocellular Carcinoma: Where We Are and Where to Go.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and is increasing in incidence. Local ablative therapy plays a leading role in HCC treatment. Radiofrequency (RFA) is one of the first-line therapies for early local ablation. Other local ablation techniques (e.g., microwave ablation, cryoablation, irreversible electroporation, phototherapy.) have been extensively explored in clinical trials or cell/animal studies but have not yet been established as a standard treatment or applied clinically. On the one hand, single treatment may not meet the needs. On the other hand, ablative therapy can stimulate local and systemic immune effects. The combination strategy of immunotherapy and ablation is reasonable. In this review, we briefly summarized the current status and progress of ablation and immunotherapy for HCC. The immune effects of local ablation and the strategies of combination therapy, especially synergistic strategies based on biomedical materials, were discussed. This review is hoped to provide references for future researches on ablative immunotherapy to arrive to a promising new era of HCC treatment.

Baseline serum TSH levels predict the absence of thyroid dysfunction in cancer patients treated with immunotherapy.

PURPOSE: Immunotherapy against immune checkpoints has significantly improved survival both in metastatic and adjuvant setting in several types of cancers. Thyroid dysfunction is the most common endocrine adverse event reported. Patients who are at risk of developing thyroid dysfunction remain to be defined. We aimed to identify predictive factors for the development of thyroid dysfunction during immunotherapy. METHODS: This is a retrospective study including a total of 68 patients who were treated with immune checkpoint inhibitors (ICIs) for metastatic or unresectable advanced cancers. The majority of patients were treated with anti-PD1 drugs in monotherapy or in combination with anti-CTLA4 inhibitors. Thyroid function and anti-thyroid antibodies, before starting immunotherapy and during treatment, were evaluated. Thyroid ultrasound was also performed in a subgroup of patients at the time of enrolment in the study. RESULTS: Eleven out of 68 patients (16.1%) developed immune-related overt thyroid dysfunction. By ROC curve analysis, we found that a serum TSH cut-off of 1.72 mUI/l, at baseline, had a good diagnostic accuracy in identifying patients without overt thyroid dysfunction (NPV = 100%, p = 0.0029). At multivariate analysis, both TSH and positive anti-thyroid antibodies (ATAbs) levels, before ICIs treatment, were independently associated with the development of overt thyroid dysfunction during immunotherapy (p = 0.0001 and p = 0.009, respectively). CONCLUSIONS: Pre-treatment serum TSH and ATAbs levels may help to identify patients at high risk for primary thyroid dysfunction. Our study suggests guidance for an appropriate timely screening and for a tailored management of thyroid dysfunctions in patients treated with ICIs.

Laser Treatment of Pancreatic Cancer with Immunostimulating Interstitial Laser Thermotherapy Protocol: Safety and Feasibility Results From Two Phase 2a Studies.

PURPOSE: Ablative techniques have emerged as new potential therapeutic options for patients with locally advanced pancreatic cancer (LAPC). We explored the safety and feasibility of using TRANBERG|Thermal Therapy System (Clinical Laserthermia Systems AB, Lund, Sweden) in feedback mode for immunostimulating Interstitial Laser Thermotherapy (imILT) protocol, the newest ablative technique introduced for the treatment of LAPC. METHODS: The safety and feasibility results after the use of imILT protocol treatment in 15 patients of a prospective series of postsystemic therapy LAPC in two high-volume European institutions, the General and Pancreatic Unit of the Pancreas Institute, of the University of Verona, Italy, and the Department of Surgical Oncology of the Institut Paoli-Calmettes of Marseille, France, were assessed. RESULTS: The mean age was 66 ± 5 years, with a mean tumor size of 34.6 (±8) mm. The median number of cycles of pre-imILT chemotherapy was 6 (6-12). The procedure was performed in 13 of 15 (86.6%) cases; indeed, in two cases, the procedure was not performed; in one, the procedure was considered technically demanding; in the other, liver metastases were found intraoperatively. In all treated cases, the procedure was completed. Three late pancreatic fistulas developed over four overall adverse events (26.6%) and were attributed to imILT. Mortality was nil. A learning curve is necessary to interpret and manage the laser parameters. CONCLUSIONS: Safety, feasibility, and device handling outcomes of using TRANBERG|Thermal Therapy System with temperature probes in feedback mode and imILT protocol on LAPC were not satisfactory. The metastatic setting may be appropriate to evaluate the hypothetic abscopal effect.#NCT02702986 and #NCT02973217.