Treatment of Schatzker Type VI Tibia Fractures Using Circular External Fixation: State of the Art, Surgical Technique and Results.

BACKGROUND: Schatzker type VI tibia fractures are usually associated with infection and surgical wound-related problems. Circular external fixation (CEF) has been shown to minimize such complications. METHODS: We pose a retrospective study of patients with Schatzker type VI fractures treated with CEF. RESULTS: Twenty-two (22) patients were included (11M/11F) with a mean age of 60.1 ± 14.9 years. According to the AO/OTA classification, two fractures (9.1%) were A2, three (13.6%) were A3, and seventeen (77.3%) were C3. Three (13.6%) of them were open. The tissue damage observed in the nineteen (86.4%) closed fractures was classified according to Tscherne (four grade I, twelve grade II, and three grade III). The mean ex-fix time was 24.1 ± 5.1 weeks. None of the patients experienced deep infections, nonunion, or malunion. The mean ROM was 111.4 ± 17.8 degrees. Although stability was achieved in all cases, 50% of them suffered osteoarthritic degeneration. Four knees required TKR at a mean of 8.77 ± 5.58 years from trauma. The mean HHS knee score was 84.2 ± 10.3 points (excellent in fifteen (68.2%) cases, good in four (18.2%), and acceptable in three (13.6%)). The mean Rasmussen radiological score was 13.3 ± 3.5 (excellent in three (13.6%) cases, good in fifteen (68.2%), and acceptable in four (18.2%)). The mean SF-12 score was 35.1 ± 10.4 points on the physical scale and 53.0 ± 10.6 points on the mental scale. CONCLUSIONS: CEF has shown itself to be a valid treatment for patients with Schatzker type VI fractures, particularly for those where the fracture is comminuted, severely displaced, open, or associated with severe soft tissue damage.

Targeting KRAS G12C Mutation in Colorectal Cancer, A Review: New Arrows in the Quiver.

Kirsten rat sarcoma virus oncogene homolog (KRAS) is the most frequently mutated oncogene in human cancer. In colorectal cancer (CRC), KRAS mutations are present in more than 50% of cases, and the KRAS glycine-to-cysteine mutation at codon 12 (KRAS G12C) occurs in up to 4% of patients. This mutation is associated with short responses to standard chemotherapy and worse overall survival compared to non-G12C mutations. In recent years, several KRAS G12C inhibitors have demonstrated clinical activity, although all patients eventually progressed. The identification of negative feedback through the EGFR receptor has led to the development of KRAS inhibitors plus an anti-EGFR combination, thus boosting antitumor activity. Currently, several KRAS G12C inhibitors are under development, and results from phase I and phase II clinical trials are promising. Moreover, the phase III CodeBreaK 300 trial demonstrates the superiority of sotorasib-panitumumab over trifluridine/tipiracil, establishing a new standard of care for patients with colorectal cancer harboring KRAS G12C mutations. Other combinations such as adagrasib-cetuximab, divarasib-cetuximab, or FOLFIRI-panitumumab-sotorasib have also shown a meaningful response rate and are currently under evaluation. Nonetheless, most of these patients will eventually relapse. In this setting, liquid biopsy emerges as a critical tool to characterize the mechanisms of resistance, consisting mainly of acquired genomic alterations in the MAPK and PI3K pathways and tyrosine kinase receptor alterations, but gene fusions, histological changes, or conformational changes in the kinase have also been described. In this paper, we review the development of KRAS G12C inhibitors in colorectal cancer as well as the main mechanisms of resistance.

Cetuximab as a Key Partner in Personalized Targeted Therapy for Metastatic Colorectal Cancer.

Cetuximab, a chimeric IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has revolutionized personalized treatment of metastatic colorectal cancer (mCRC) patients. This review highlights the mechanism of action, characteristics, and optimal indications for cetuximab in mCRC. Cetuximab has emerged as a pivotal partner for novel therapies in specific molecular subgroups, including BRAF V600E, KRAS G12C, and HER2-altered mCRC. Combining cetuximab with immunotherapy and other targeted agents further expands the therapeutic landscape, offering renewed hope for mCRC patients who face the development of resistance to conventional therapies. Ongoing clinical trials have continued to uncover innovative cetuximab-based treatment strategies, promising a brighter future for mCRC patients. This review provides a comprehensive overview of cetuximab's role and its evolving importance in personalized targeted therapy of mCRC patients, offering valuable insights into the evolving landscape of colorectal cancer treatment.

Negative Hyperselection of Patients with HER2+ and RAS Wild-Type Metastatic Colorectal Cancer Receiving Dual HER2 Blockade: the PRESSING-HER2 Study.

PURPOSE: To demonstrate the negative prognostic impact of a panel of genomic alterations (PRESSING-HER2 panel) and lack of HER2 amplification by next-generation sequencing (NGS) in patients with HER2+, RAS wild-type metastatic colorectal cancer receiving dual HER2 blockade. EXPERIMENTAL DESIGN: The PRESSING-HER2 panel of HER2 mutations/rearrangements and RTK/MAPK mutations/amplifications was assessed by NGS. HER2 amplification was confirmed by NGS if copy-number variation (CNV) was ≥ 6. With a case-control design, hypothesizing 30% and 5% PRESSING-HER2 positivity in resistant [progression-free survival (PFS) <4 months and no RECIST response] versus sensitive cohorts, respectively, 35 patients were needed per group. RESULTS: PRESSING-HER2 alterations included HER2 mutations/rearrangements, EGFR amplification, and BRAF mutations and had a prevalence of 27% (9/33) and 3% (1/35) in resistant versus sensitive patients (P = 0.005) and 63% predictive accuracy. Overall, HER2 nonamplified status by NGS had 10% prevalence. Median PFS and overall survival (OS) were worse in PRESSING-HER2+ versus negative (2.2 vs. 5.3 months, P < 0.001; 5.4 vs. 14.9 months, P = 0.001) and in HER2 nonamplified versus amplified (1.6 vs. 5.2 months, P < 0.001; 7.4 vs. 12.4 months, P = 0.157). These results were confirmed in multivariable analyses [PRESSING-HER2 positivity: PFS HR = 3.06, 95% confidence interval (CI), 1.40-6.69, P = 0.005; OS HR = 2.93, 95% CI, 1.32-6.48, P = 0.007]. Combining PRESSING-HER2 and HER2 CNV increased the predictive accuracy to 75%. CONCLUSIONS: PRESSING-HER2 panel and HER2 nonamplified status by NGS warrant validation as potential predictive markers in this setting. See related commentary by Raghav et al., p. 260.

The impact of clinical and translational research on the quality of life during the metastatic colorectal cancer patient journey.

The journey of metastatic colorectal cancer patients is complex and challenging, requiring coordination and collaboration between multiple healthcare providers. Understanding patients' needs, fears, feelings, concerns, and behaviors is essential for providing individualized patient-centered care. In recent years, mCRC patients have experienced improvements in clinical outcomes, from 16 months of overall survival to 32 months, thanks to research. However, there is still room for improvement, and integrating clinical and translational research into routine practice can help patients benefit from treatments and techniques that would not be an option. In the Journey of mCRC patients, living well with cancer and quality of life becomes a priority given the outcomes of the disease. Patient reported outcomes (PRO) and Patient Reported Outcome Measures (PROMs) are becoming therefore new estimands in Oncology. Patient advocates represent important figures in this process by prioritizing issues and research questions; evaluating research designs and the performance of the research; the analysis and interpretation of data; and how results are disseminated. Multidisciplinary Tumor Boards and shared decision-making is essential for designing treatment strategies for individual patients. Quality of Life is often prioritized only when it comes to refractory advanced disease and end-of-life care, but it has to be integrated from the beginning, as the emotional impact of diagnosis leads to a vulnerable situation where patients' needs and preferences can be easily overseen. First-line treatment will be chosen among more treatment options than subsequent lines, with longer progression-free survival and a bigger impact on the outcomes. Practicing patient-centered care and optimizing first-line treatment for colorectal cancer patients requires a comprehensive understanding of patient experience and treatment outcomes, which can guide clinical practice and inform regulatory decisions for the benefit of patients.

Predictive Impact of RNF43 Mutations in Patients With Proficient Mismatch Repair/Microsatellite Stable BRAFV600E-Mutated Metastatic Colorectal Cancer Treated With Target Therapy or Chemotherapy.

PURPOSE: Target therapy (TT) with encorafenib plus cetuximab is a standard option in patients with BRAFV600E-mutated (mut) pretreated metastatic colorectal cancer (mCRC). Recently, mutations in RNF43, encoding a negative regulator of the WNT pathway, were associated with longer progression-free survival (PFS) and overall survival (OS) in patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) BRAFV600E-mut mCRC treated with TT. Here, we explored the effect of RNF43 mutations on the efficacy of second-line TT versus standard chemotherapy (CT). METHODS: A retrospective cohort of patients with pMMR/MSS BRAFV600E-mut tumors, available RNF43 mutational status, and treated with second-line TT or oxaliplatin- and/or irinotecan-based CT was analyzed. RESULTS: One hundred thirty-two patients with pMMR/MSS BRAFV600E-mut mCRC were included. RNF43 was found mut in 34 (26%) cases. Among RNF43 mutants, TT was associated with longer PFS (7.7 v 3.0 months; P = .002) and higher overall response rate (ORR; 45% v 0%; P = .009) compared with CT. Conversely, among RNF43 wild-type (wt) patients, only a trend for longer PFS (4.5 v 3.7 months; P = .064) favoring TT, with no differences in ORR (P = .14), was observed. After excluding 36 patients receiving TT in third line or beyond, a longer OS (19.4 v 10.1 months; P = .022) and a numerically OS advantage (10.6 v 6.6 months; P = .068) were reported for TT both in the RNF43-mut and in the RNF43 wt groups. However, no interaction effect was reported between RNF43 mutational status and treatment in ORR (Pinteraction = .96), PFS (Pinteraction = .13), and OS (Pinteraction = .44). CONCLUSION: Patients with pMMR/MSS BRAFV600E-mut mCRC achieve benefit from TT versus CT independently of RNF43 mutational status, although a higher magnitude of benefit from TT is observed in RNF43-mut tumors. These findings deserve confirmation in concluded and ongoing randomized trials.

Immunotherapy for Colorectal Cancer with High Microsatellite Instability: The Ongoing Search for Biomarkers.

Microsatellite instability (MSI) is a biological condition associated with inflamed tumors, high tumor mutational burden (TMB), and responses to immune checkpoint inhibitors. In colorectal cancer (CRC), MSI tumors are found in 5% of patients in the metastatic setting and 15% in early-stage disease. Following the impressive clinical activity of immune checkpoint inhibitors in the metastatic setting, associated with deep and long-lasting responses, the development of immune checkpoint inhibitors has expanded to early-stage disease. Several phase II trials have demonstrated a high rate of pathological complete responses, with some patients even spared from surgery. However, in both settings, not all patients respond and some responses are short, emphasizing the importance of the ongoing search for accurate biomarkers. While various biomarkers of response have been evaluated in the context of MSI CRC, including B2M and JAK1/2 mutations, TMB, WNT pathway mutations, and Lynch syndrome, with mixed results, liver metastases have been associated with a lack of activity in such strategies. To improve patient selection and treatment outcomes, further research is required to identify additional biomarkers and refine existing ones. This will allow for the development of personalized treatment approaches and the integration of novel therapeutic strategies for MSI CRC patients with liver metastases.

Unravelling the Complexity of Colorectal Cancer: Heterogeneity, Clonal Evolution, and Clinical Implications.

Colorectal cancer (CRC) is a global health concern and a leading cause of death worldwide. The disease's course and response to treatment are significantly influenced by its heterogeneity, both within a single lesion and between primary and metastatic sites. Biomarkers, such as mutations in KRAS, NRAS, and BRAF, provide valuable guidance for treatment decisions in patients with metastatic CRC. While high concordance exists between mutational status in primary and metastatic lesions, some heterogeneity may be present. Circulating tumor DNA (ctDNA) analysis has proven invaluable in identifying genetic heterogeneity and predicting prognosis in RAS-mutated metastatic CRC patients. Tumor heterogeneity can arise from genetic and non-genetic factors, affecting tumor development and response to therapy. To comprehend and address clonal evolution and intratumoral heterogeneity, comprehensive genomic studies employing techniques such as next-generation sequencing and computational analysis are essential. Liquid biopsy, notably through analysis of ctDNA, enables real-time clonal evolution and treatment response monitoring. However, challenges remain in standardizing procedures and accurately characterizing tumor subpopulations. Various models elucidate the origin of CRC heterogeneity, highlighting the intricate molecular pathways involved. This review focuses on intrapatient cancer heterogeneity and genetic clonal evolution in metastatic CRC, with an emphasis on clinical applications.

Treatment of BRAF-V600E mutant metastatic colorectal cancer: new insights and biomarkers.

INTRODUCTION: The presence of a BRAF-V600E mutation in metastatic colorectal cancer (mCRC) is observed in approximately 12% of cases and is associated with poor prognosis and aggressive disease. Unlike melanoma, the development of successful BRAF blockade in colorectal cancer has been complex. The phase III BEACON trial made significant progress in the development of BRAF inhibitors by establishing encorafenib-cetuximab as the new standard of care for patients with mCRC who have progressed to one or two previous lines of treatment. Nonetheless, not all patients respond to encorafenib-based combinations, and some responses are short-lived. Identifying new strategies to boost antitumor activity and improve survival is paramount. AREAS COVERED: The development of targeted therapy for BRAF-V600E mCRC starting with BRAF inhibitors as monotherapy through novel combinations with anti-VEGF or anti-PD1 agents to enhance antitumor activity is reviewed, with a particular focus on the development of predictive and prognostic biomarkers. EXPERT OPINION: There is a crucial need to better understand tumor biology and develop accurate and reliable biomarkers to enhance the antitumor activity of encorafenib-based combinations. The RNF43 mutation is an accurate and reliable predictive biomarker of response, and combinations that target crosstalk between the MAPK pathway, the immune system, and WNT pathways seem promising.

Impact of the COVID-19 pandemic in the early-onset colorectal cancer.

The COVID19 pandemic has affected the spectrum of cancer care worldwide. Early onset colorectal cancer (EOCRC) is defined as diagnosis below the age of 50. Patients with EOCRC faced multiple challenges during the COVID19 pandemic and in some institutions it jeopardized cancer diagnosis and care delivery. Our study aims to identify the clinicopathological features and outcomes of patients with EOCRC in our Centre during the first wave of the pandemic in comparison with the same period in 2019 and 2021. Patients with EOCRC visited for the first time at Vall d'Hebron University Hospital in Spain from the 1st March to 31st August of 2019, 2020 and 2021 were included in the analysis. 177 patients with EOCRC were visited for the first time between 2019 and 2021, of which 90 patients met the inclusion criteria (2019: 30 patients, 2020: 29 patients, 2021: 31 patients). Neither differences in frequency nor in stage at diagnosis or at first visit during the given periods were observed. Of note, indication of systemic therapy in the adjuvant or metastatic setting was not altered. Days to treatment initiation and enrollment in clinical trials in this subpopulation was not affected due to the COVID-19 outbreak.

Liver transplantation in metastatic colorectal cancer: are we ready for it?

Colorectal cancer (CRC) is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Five-year overall survival remains modest among patients with metastatic CRC (mCRC) treated with conventional therapies however, liver transplantation in a highly selected population can improve clinical outcomes with an impressive 5-year overall survival of 83%. Despite liver transplantation appearing to be a promising therapeutical option for well-selected patients with mCRC with the liver-limited disease, these data come from small monocentric trials which included a heterogeneous population. Currently, several clinical trials are evaluating liver transplantation in this scenario, aiming for a more accurate patient selection by integrating liquid biopsy, tissue profiling, and nuclear medicine to the already known clinical biomarkers that eventually may lead to a survival improvement. In this paper, the clinical outcomes and inclusion criteria from the most relevant clinical trials and clinical series involving liver transplantation in patients with liver-limited disease colorectal cancer are reviewed as well as the trials currently recruiting.

Enterobacter cloacae Infection After Surgical Treatment of Ankle Fractures, a Multicenter Observational Study.

BACKGROUND: Infection is one of the challenging complications after open reduction and internal fixation for ankle fractures. Previously published case series conclude that Staphylococcus aureus is the most frequent causative microorganism. An unexpected increase in Enterobacter cloacae infections after this surgery was observed in a preliminary analysis of data at the promoting center of the study. In traumatology, its incidence has been reported in chronic osteomyelitis, prosthetic infections, septic osteoarthritis, open fractures in children and adults, and fractures other than the ankle. Because of this unexpected finding, we decided to perform this study to analyze the demographic and microbiological variables of acute osteosynthesis infection after ankle fracture and determine the distinctive features of the patients with E cloacae infection. METHODS: We performed a retrospective multicenter study including 4 university hospitals. All patients diagnosed with acute osteosynthesis infection after ankle fracture fixation between January 2015 and December 2018 were included. We analyzed demographic data, type of fracture, surgical technique, and microorganisms responsible for the infection. We performed a descriptive statistical analysis of the variables. Univariate and multivariate regression analysis were performed to compare patients with E cloacae infection to patients with infection caused by other microorganisms. RESULTS: A total of 65 patients were included. A predominance of polymicrobial infections (24.62%), followed by infections caused by S aureus (23.07%) and E cloacae (23.07%) was observed. When E cloacae isolated in polymicrobial infections were added, the incidence of E cloacae as a causative microorganism increased to 32.3%. Patients with E cloacae infection were older (64/53, P = .008) and had a higher requirement of negative-pressure therapy after surgical debridement (71%/40%, P = .017). CONCLUSION: A high incidence of E cloacae infections was observed. Patients with E cloacae infection were generally older and required a higher use of negative-pressure therapy after debridement. LEVEL OF EVIDENCE: Level V, mechanism-based reasoning.

Advances in immune checkpoint inhibitor combination strategies for microsatellite stable colorectal cancer.

Immune checkpoint inhibitors have reshaped the prognostic of several tumor types, including metastatic colorectal tumors with microsatellite instability (MSI). However, 90-95% of metastatic colorectal tumors are microsatellite stable (MSS) in which immunotherapy has failed to demonstrate meaningful clinical results. MSS colorectal tumors are considered immune-cold tumors. Several factors have been proposed to account for this lack of response to immune checkpoint blockade including low levels of tumor infiltrating lymphocytes, low tumor mutational burden, a high rate of WNT/ß-catenin pathway mutations, and liver metastases which have been associated with immunosuppression. However, studies with novel combinations based on immune checkpoint inhibitors are showing promising activity in MSS colorectal cancer. Here, we review the underlying biological facts that preclude immunotherapy activity, and detail the different immune checkpoint inhibitor combinations evaluated, along with novel immune-based therapies, to overcome innate mechanisms of resistance in MSS colorectal cancer.

Transcriptomic profiling reveals distinct subsets of immune checkpoint inhibitor induced myositis.

OBJECTIVES: Inflammatory myopathy or myositis is a heterogeneous family of immune-mediated diseases including dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Immune checkpoint inhibitors (ICIs) can also cause myositis (ICI-myositis). This study was designed to define gene expression patterns in muscle biopsies from patients with ICI-myositis. METHODS: Bulk RNA sequencing was performed on 200 muscle biopsies (35 ICI-myositis, 44 DM, 18 AS, 54 IMNM, 16 IBM and 33 normal muscle biopsies) and single nuclei RNA sequencing was performed on 22 muscle biopsies (seven ICI-myositis, four DM, three AS, six IMNM and two IBM). RESULTS: Unsupervised clustering defined three distinct transcriptomic subsets of ICI-myositis: ICI-DM, ICI-MYO1 and ICI-MYO2. ICI-DM included patients with DM and anti-TIF1γ autoantibodies who, like DM patients, overexpressed type 1 interferon-inducible genes. ICI-MYO1 patients had highly inflammatory muscle biopsies and included all patients that developed coexisting myocarditis. ICI-MYO2 was composed of patients with predominant necrotising pathology and low levels of muscle inflammation. The type 2 interferon pathway was activated both in ICI-DM and ICI-MYO1. Unlike the other types of myositis, all three subsets of ICI-myositis patients overexpressed genes involved in the IL6 pathway. CONCLUSIONS: We identified three distinct types of ICI-myositis based on transcriptomic analyses. The IL6 pathway was overexpressed in all groups, the type I interferon pathway activation was specific for ICI-DM, the type 2 IFN pathway was overexpressed in both ICI-DM and ICI-MYO1 and only ICI-MYO1 patients developed myocarditis.

Association of immune-related adverse events with the outcomes of immune checkpoint inhibitors in patients with dMMR/MSI-H metastatic colorectal cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) show a tremendous activity in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), but a consistent fraction of patients does not respond. Prognostic/predictive markers are needed. Despite previous investigations in other tumor types, immune-related adverse events (irAEs) have not been well evaluated in patients with MSI-H cancers treated with ICIs. METHODS: We conducted an international cohort study at tertiary cancer centers collecting clinic-pathological features from 331 patients with MSI-H mCRC treated with ICIs. Of note, the irAEs were summarized using a 'burden score' constructed in a way that the same score value could be obtained by cumulating many low-grade irAEs or few high-grade irAEs; as a result, the lower the burden the better. Clearly, the irAE burden is not a baseline information, thus it was modeled as a time-dependent variable in univariable and multivariable Cox models. RESULTS: Among 331 patients, irAEs were reported in 144 (43.5%) patients. After a median follow-up time of 29.7 months, patients with higher burden of skin, endocrine and musculoskeletal irAEs (the latter two's effect was confirmed at multivariable analysis) had longer overall survival (OS), as opposed to gastrointestinal, pneumonitis, neurological, liver, renal and other irAEs, which showed an harmful effect. Similar results were observed for progression-free survival (PFS). Based on the results retrieved from organ-specific irAEs, 'aggregated' burden scores were developed to distinguish 'protective' (endocrine and musculoskeletal) and 'harmful' (gastrointestinal, pneumonitis, neurological, hepatic) irAEs showing prognostic effects on OS and PFS. CONCLUSIONS: Our results demonstrate that not all irAEs could exert a protective effect on oncologic outcome. An easy-to-use model for ICIs toxicity (burden score of protective and harmful irAEs) may be used as surrogate marker of response.

Paeniclostridium sordellii-associated peripartum metritis in goats.

Paeniclostridium sordellii is involved in enteric and histotoxic infections in several animal species. In humans, P. sordellii has been linked to gynecological disease, an association not previously investigated in animals. To unveil a potential association of P. sordellii with veterinary reproductive disease, a retrospective search of the database of the California Animal Health and Food Safety Laboratory System (1990-2020) was conducted and identified 9 cases of goats with P. sordellii-associated metritis or endometritis that were confirmed by immunofluorescence antibody test and/or bacterial isolation, and often co-colonized by Escherichia coli. Six of 9 does were also copper deficient. Polymerase chain reaction (PCR) on formalin-fixed, paraffin-embedded uterine tissue identified the sordellilysin gene in all 9 cases, and the lethal toxin gene in 4. Our findings suggest goats could be predisposed to P. sordellii-associated endometritis/metritis and toxemia when co-infected with E. coli. The role of mineral deficiencies influencing vulnerability to puerperal bacterial infections in goats is possible but remains undetermined. To our knowledge, this is the first report documenting the association of P. sordellii with veterinary gynecological disease.

Pharmacokinetics and pharmacodynamics of approved monoclonal antibody therapy for colorectal cancer.

INTRODUCTION: The introduction of monoclonal antibodies to the chemotherapy backbone treatment has challenged the paradigm of metastatic colorectal cancer (mCRC) treatment. Their mechanism of action and pharmacokinetics are complex but important to understand in order to improve patient selection and treatment outcomes for mCRC population. AREAS COVERED: This review examines the scientific data, pharmacodynamics, and pharmacokinetics of approved monoclonal antibodies used to treat mCRC patients, including agents targeting signaling via VEGFR (bevacizumab and ramucirumab), EGFR (cetuximab and panitumumab), HER2/3 target therapy, and immunotherapy agents such as pembrolizumab or nivolumab. Efficacy and mechanism of action of bispecific antibodies are also covered. EXPERT OPINION: mCRC is a heterogeneous disease and the optimal selection and sequence of treatments is challenging. Monoclonal antibodies have complex pharmacokinetics and pharmacodynamics, with important interactions between them. The arrival of bioequivalent molecules to the market increases the need for the characterization of pharmacokinetics and pharmacodynamics of classic monoclonal antibodies to reach bioequivalent novel molecules.

Management of Cancer-Associated Myositis.

Purpose of the Review: Cancer-associated myositis (CAM) is defined as when cancer appears within 3 years of myositis onset. Dermatomyositis and seronegative immune-mediated necrotizing myopathy are the phenotypes mostly related to cancer. In general, treatment principles in myositis patients with and without CAM are similar. However, some aspects of myositis management are particular to CAM, including (a) the need for a multidisciplinary approach and a close relationship with the oncologist, (b) the presence of immunosuppressive and antineoplastic drug interactions, and (c) the role of the long-term immunosuppressive therapy as a risk factor for cancer relapse or development of a second neoplasm. In this review, we will also discuss immunotherapy in patients treated with checkpoint inhibitors as a treatment for their cancer. Recent Findings: Studies on cancer risk in patients treated with long-term immunosuppressive drugs, in autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis, and in solid organ transplant recipients have shed some light on this topic. Immunotherapy, which has been a great advance for the treatment of some types of malignancy, may be also of interest in CAM, given the special relationship between both disorders. Summary: Management of CAM is a challenge. In this complex scenario, therapeutic decisions must consider both diseases simultaneously. Supplementary Information: The online version contains supplementary material available at 10.1007/s40674-022-00197-2.