Immunotherapy-related Toxicity Research Articles

Abstract 2801: Identifying gut microbial determinants of clonal hematopoiesis of indeterminate potential (CHIP) in immunotherapy treated melanoma patients

Abstract INTRO: Clonal hematopoiesis (CH) of indeterminate potential (CHIP) is associated with poor outcomes in those with non-hematologic cancers. CH mutated macrophages and neutrophils have increased capacity to home to peripheral tissues, driving local inflammation; they are also implicated in immunotherapy related toxicity. The relationship between CH and the microbiome in those treated with immunotherapy is not well understood. RESULTS: 35 patients with stage IV melanoma treated with upfront immunotherapy; treatment and cohort characteristics are below (Table 1). We performed error corrected duplex sequencing on peripheral blood mononuclear cells using a panel previously validated for CH mutations. With a cutoff of 0.5% variant allele frequency (VAF), among 10 CHIP positive patients, we found mutations in TET2 (8/10), DNMT3A (7/10), PPM1D (2/10), and JAK2 (1/10). There was no difference in either survival or response based on CHIP status (Log-Rank Chi-Square p=0.44); however, CHIP positivity was associated with greater microbiome richness as measured by alpha diversity (p=0.0012 Shannon diversity) and distinct structural/compositional diversity vs CHIP negative patients as measured by beta diversity (p=0.032, R Squared= 0.045). We inferred KEGG pathway activity from whole genome sequencing and identified that CHIP positive patients were enriched for exopolysaccharide biosynthesis while CHIP negative patients had higher expression of nucleotide sugars biosynthesis and amino acid metabolism pathways. DISCUSSION: In patients treated with immunotherapy for melanoma, microbiome diversity signatures correlate with presence of CHIP. The analysis suggests that there are distinct taxonomic and functional features defining CHIP positivity. The effect of these cells in the tumor microenvironment and their role in immunotherapy response requires further exploration. Citation Format: Eleanor A. Fallon, Samuel Urrutia, Reed Ayabe, Manoj Chelvanambi, Ashish Damania, Sarah Johnson, Tomoyuki Tanaka, Zongrui Li, Yongwoo David Seo, Samuel Cass, Matthew C. Wong, Nadim Ajami, Jennifer Wargo, Koichi Takahashi. Identifying gut microbial determinants of clonal hematopoiesis of indeterminate potential (CHIP) in immunotherapy treated melanoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2801.

Durvalumab and tremelimumab before surgery in patients with hormone receptor positive, HER2-negative stage II-III breast cancer.

A clinical trial was conducted to assess the feasibility of enrolling patients with Stage II or III hormone receptor positive (HR+)/HER2-negative breast cancer to pre-operative dual PD-L1/CTLA-4 checkpoint inhibition administered prior to neoadjuvant chemotherapy (NACT). Eight eligible patients were treated with upfront durvalumab and tremelimumab for two cycles. Patients then received NACT prior to breast surgery. Seven patients had baseline and interval breast ultrasounds after combination immunotherapy and the responses were mixed: 3/7 patients experienced a ≥30% decrease in tumor volume, 3/7 a ≥30% increase, and 1 patient had stable disease. At the time of breast surgery, 1/8 patients had a pathologic complete response (pCR). The trial was stopped early after 3 of 8 patients experienced immunotherapy-related toxicity or suspected disease progression that prompted discontinuation or a delay in the administration of NACT. Two patients experienced grade 3 immune-related adverse events (1 with colitis, 1 with endocrinopathy). Analysis of the tumor microenvironment after combination immunotherapy did not show a significant change in immune cell subsets from baseline. There was limited benefit for dual checkpoint blockade administered prior to NACT in our study of 8 patients with HR+/HER2-negative breast cancer.

Detectable ctDNA at the time of treatment cessation of ipilimumab and nivolumab for toxicity predicts disease progression in advanced melanoma patients.

Immune checkpoint inhibition (ICI) has led to unprecedented outcomes for melanoma patients but is associated with toxicity. ICI resumption after high grade irAEs poses a significant challenge in the clinical management of melanoma patients and there are no biomarkers that can help identify patients that might benefit from resuming treatment. This study aims to determine if circulating tumor DNA (ctDNA) levels at the time of treatment-limiting irAE could guide treatment decisions in this clinical context. This is a retrospective exploratory biomarker study from 34 patients treated with combination ICI for stage IV melanoma. Patients had a treatment-limiting toxicity and a baseline plasma collection prior to commencing ICI and within 6 weeks of stopping therapy. Blood samples were tested for ctDNA at baseline and cessation therapy. Median progression free survival (PFS) and overall survival (OS) have not been reached (24-month PFS rate 54% and OS rate 72.3%). PD occurred in 47% (16/34) of patients. Median PFS with detectable ctDNA from plasma collected at the time of toxicity was 6.5 months while not reached (NR) with undetectable levels (HR: 4.0, 95% CI 0.95-17.5, p=0.0023). Median OS with detectable ctDNA at cessation for toxicity was 19.4 months and NR for undetectable ctDNA (HR: 3.9, 95%CI 20.8-18.6, p=0.024). Positive ctDNA at the time of cessation was highly specific (specificity 0.94, 95% CI 0.74-0.99, PPV 0.88, 95% CI 0.53-0.99). However, ctDNA negativity has low sensitivity as a predictor of ongoing disease control (sensitivity 0.437, 95% CI 0.23-0.67). Notably, 4/9 (44%) ctDNA negative patients who had disease progression had brain only disease progression. Undetectable ctDNA and CR on imaging after stopping immunotherapy for toxicity results in high rates of long-term durable control. For patients with immunotherapy related toxicity, who have persistent ctDNA at 8 - 12 weeks, the risk of disease progression is significant.

Dissecting the role of the gut microbiome and fecal microbiota transplantation in radio- and immunotherapy treatment of colorectal cancer.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and poses a major burden on the human health worldwide. At the moment, treatment of CRC consists of surgery in combination with (neo)adjuvant chemotherapy and/or radiotherapy. More recently, immune checkpoint blockers (ICBs) have also been approved for CRC treatment. In addition, recent studies have shown that radiotherapy and ICBs act synergistically, with radiotherapy stimulating the immune system that is activated by ICBs. However, both treatments are also associated with severe toxicity and efficacy issues, which can lead to temporary or permanent discontinuation of these treatment programs. There's growing evidence pointing to the gut microbiome playing a role in these issues. Some microorganisms seem to contribute to radiotherapy-associated toxicity and hinder ICB efficacy, while others seem to reduce radiotherapy-associated toxicity or enhance ICB efficacy. Consequently, fecal microbiota transplantation (FMT) has been applied to reduce radio- and immunotherapy-related toxicity and enhance their efficacies. Here, we have reviewed the currently available preclinical and clinical data in CRC treatment, with a focus on how the gut microbiome influences radio- and immunotherapy toxicity and efficacy and if these treatments could benefit from FMT.

NCCN Highlights Best Practices for Challenges in Oncology

NCCN Highlights Best Practices for Challenges in Oncology

Phase Ib of pembrolizumab (pem) in combination with stereotactic body radiotherapy (SBRT) for resectable liver oligometastatic MMR-proficient (pMMR) colorectal cancer (CRC): Final results.

161 Background: SBRT is a standard treatment option for oligometastatic CRC and is associated with an increase in immunogenic antigen release and influx of immune cells. We hypothesized that radiation would enhance the immunogenicity of pMMR CRC and potentiate the effectiveness of PD-1 blockade. This phase Ib study examined the safety and efficacy of the sequential combination of SBRT and Pem in patients (pts) undergoing resection of their disease. Additionally, the accumulation and proteolysis of versican (VCAN), an immunoregulatory tumor matrix proteoglycan was examined as a novel immunotherapy biomarker. Proteolysis of VCAN results in the release of an immunostimulatory fragment, versikine. Cancers with low VCAN and high versikine (VCAN proteolysis predominant (VPP)) are hypothesized to respond better to immunotherapies. Methods: Eligibility criteria included resectable liver-confined metastatic pMMR CRC. Prior surgery and systemic chemotherapy were allowed. Subjects received sequential SBRT and cycle 1 of Pem prior to operative management and adjuvant Pem. The primary objectives were to determine the safety/tolerability of this regimen and the recurrence free survival (RFS) at 1 year following operative management. Correlative studies examined tumor infiltrating CD8+ T lymphocytes (TILs), VCAN, and versikine using immunohistochemistry. Results: 15 pts (median age 61.5 [range 39-69], 26% female) were enrolled. All pts had prior FOLFOX. The number of liver lesions ranged from 1-6. SBRT median dose was 50 Gy (40-60 Gy) to 1-2 liver lesions. Grade 3/4 AEs included one case of biliary tract injury and biloma, and one case of G3 hypophosphatemia. No grade 3/4 immune-related AEs occurred. All pts completed a minimum follow-up of 1 year post resection (median follow-up 41 months [range 15-64]). In the intention to treat analysis, the 1 year RFS was 67% (historic control 50%), 40% of patients remained cancer free, and 67% of pts are still alive. 2 of 3 pts with BRAF V600E mutations have had early recurrences. 2 pts had VCAN high tumors and both recurred prior to 1 year. 6 pts had VPP cancers and 83% were recurrence free at 1 year and 66% are currently without evidence of cancer. Conclusions: The combination of SBRT with Pem was well tolerated with no signal of increased immunotherapy-related toxicity. This study met its primary endpoint and this regimen deserves further investigation in confirmatory studies. Additionally, VCAN accumulation and proteolysis are promising biomarkers in this setting. Clinical trial information: NCT02837263 .

Chimeric Antigen Receptor T Cell Therapy for Acute Leukemia.

The worldwide use of CD19 chimeric antigen receptor (CAR)-T cells has increased the response rate in patients with refractory or relapsed B-cell acute lymphoblastic leukemia. Clinical practice has become much safer with the help of immunotherapy-related toxicity management guidelines, such as the ASTCT consensus grading system. Tocilizumab and steroids are the major interventions for controlling cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). New drugs and interventions for uncontrolled CRS and ICANS, including JAK1/2 inhibitors, have also been investigated. The combination of ruxolitinib and steroids effectively controlled severe CRS without impeding CAR-T cell expansion. Patients with refractory CNS3 status and CNS masses were excluded from the clinical trials because of the high risk of severe ICANS. Intracranial injections of steroids and Ommaya capsule implantation were effective. For some heavily treated patients, the difficulties in CAR-T cell manufacturing and expansion may be resolved by combination with blinatumumab. Relapse is a major concern after CAR-T therapy, and combination interventions, such as allogeneic stem cell transplantation, dual-target CAR-T cell therapies, and sequential CD19/22 CAR-T infusion, have been investigated in many centers. For T-lineage-targeted CAR-T therapies, the CAR T-cell fratricide can be overcome using many techniques. The efficacy and safety of CD7+ CAR-T cell therapy have been widely reported in recent years. A high response rate can be achieved when the immune reconstitution is prolonged. Infections, particularly viral reactivations, should be carefully monitored, as relapses are another potential issue. Switching targets and eliminating residual CD7+ CAR-T cells in the blood are key points for patients who relapse after CD7+ CAR-T cell therapy. CAR-T cell therapies for AML have not been investigated in a large-scale cohort, except for CD19-positive AML with the AML1-ETO fusion gene.

Myositis-myasthenic overlap syndrome triggered by pembrolizumab in a melanoma patient: a case report and brief review of the literature

Background: In the era of precision medicine, immune checkpoint inhibitors (ICIs) have dramatically changed the therapeutic approach toward advanced cancers. Despite an undeniably therapeutic benefit, ICIs have unique and uncharted toxicities known as immune-related adverse events (irAEs). Case Presentation: We report a rare overlap syndrome of inflammatory and necrotizing myopathy with a superimposed myasthenia-like syndrome in a melanoma patient who had received the first dose of pembrolizumab 22 days before symptoms onset. The patient initially presented with muscle weakness and ptosis and rapidly progressed to tetraparesis, extrinsic ophthalmoplegia, dysarthria, dysphagia, and respiratory difficulty with a short-term need for non-invasive ventilation and nasogastric intubation. Transitory myocarditis was also diagnosed. One month after hospital discharge, the patient still exhibits mild dysarthria, dysphagia, and ptosis and needs walking assistance. Conclusion: Although rare, neuromuscular irAEs impose a notable burden on morbidity and even mortality. Early recognition of symptoms and prompt intervention are crucial for the management of immunotherapy-related toxicity.

Outcomes of immunotherapy-related hepatotoxicity from a multi-disciplinary toxicity team.

Despite the efficacy of immune checkpoint inhibitors (ICIs), adverse events including hepatotoxicity limit their ongoing use. We investigated the outcomes and management of patients with immune-mediated hepatitis (IMH) and clinical predictors of toxicity resolution. Patients referred to our multidisciplinary immunotherapy-related toxicity group from August 2017 to December 2020 for IMH were evaluated. Toxicity was defined according to CTCAEv4.0. IMH resolution was defined as liver enzyme normalization after steroid initiation. Thirty-three patients were included in the study, 62% female, and 71% Caucasian. The most common ICI used was PD-1/PD-L1 (76%). Peak IMH occurred at a median of 89 [45,193] days, for which most patients received 1-2mg/kg/day prednisone equivalent with 35% requiring MMF. Median follow-up was 123 [33,472] days with IMH resolution seen in 48% of patients at a median of 111 [41,214] days. While high-dose steroid use was not associated with IMH resolution, liver enzyme improvement one week after steroids predicted resolution in univariate analysis (p = 0.041). All 11 patients without IMH resolution died from cancer progression or complications with three patients having acute liver failure. Available liver biopsies showed bile duct injury, with varying degrees of portal and lobular inflammation. IMH improvement one week after steroid initiation may predict ultimate IMH resolution.

Striking effect of low-dose radiotherapy combined with PD-1 blockade on small cell lung cancer in mice and refractory patients (Achilles Study).

e20608 Background: Immune checkpoint inhibitors (ICIs) provide a durable and long-term benefit but still unsatisfactory clinical efficacy for extensive-stage small cell lung cancer (ES-SCLC). An optimized dose and schedule of radiotherapy for ES-SCLC remain to be studied. We hypothesized that the addition of low-dose radiotherapy (LDRT) to ICI could improve the efficacy of ES-SCLC. Methods: In SCLC bearing mice, the tumor was irradiated with LDRT in dose-escalation starting at 3Gy×1 fractions (f) up to 3Gy×7f, and combined with PD-1 antibody injection (0.2mg/mouse, i.p, every 3 days). Mice were followed for tumor growth and survival. The tumor microenvironment was dynamically analyzed every 3 days till day 18 by flow cytometry and immunofluorescence. 15 patients (pts) with relapsed ES-SCLC who received the treatment with LDRT and PD-1 blockade were retrospectively reviewed. Results: LDRT with 3Gy×5f delivered over 5 days (LDRT15Gy/5f) was determined to be the optimized dose when combined with PD-1 blockade. Combined group exhibited obvious growth retardation and prolonged survival compared to either monotherapy.The most robust infiltration of T cells in combined group was observed on day 9 after start of treatment. Bulk and single-cell RNA-seq showed significant immune cells infiltration, predominately CD8+ T cells and M1 macrophage. The activation and degranulation of CD8+ T cells in combination group were enhanced. Intra-tumoral CD8+ T cells were mainly assigned to effector memory (Tem) cells, then exhausted precursor (Texp) cells and exhausted (Tex) cells. Pseudo-time analysis supported a state evolution model that CD8+ Tem cells differentiate into intra-tumoral CD8+ Tex cells through an intermediate CD8+ Texp state. Tumor cells were divided into clusters 0, 1, and 2. Cluster 0 nearly disappeared while the proportion of cluster 1 increased in combination therapy. Cluster 1 enriched inflammatory response pathways and higher expression of MHC class I versus clusters 0 and 2. Additionally, the density of intra-tumoral microvessel was decreased, while vascular perfusion and the number of pericyte-covered vessels increased in combined group. Correspondingly, 15 recurrent ES-SCLC pts who treated with up-front LDRT15Gy/5f plus PD-1 blockade showed an ORR of 80%. Median PFS and OS were 4.3 months and 10.9 months. PFS rates at 6, 12 and 24 months were 40%, 20% and 6.7%, and OS rates were 60%, 40% and 24%, respectively. No patient experienced above grade 4 radiation- and immunotherapy-related toxicity. Conclusions: Our study is the first report of the synergistic effect of LDRT15Gy/5f and PD-1 blockade in SCLC mice model and recurrent ES-SCLC pts. The LDRT15Gy/5f demonstrates both immunologic adjuvant and cytotoxic effect on SCLC, and is safe and feasible in clinical pts. Further translational research, Match trial (NCT04622228), is ongoing.

Good outcomes after aggressive treatment of immune checkpoint inhibitor related myasthenia gravis: a case series

IntroductionMyasthenia gravis (MG) is a rare but potentially life-threatening complication of immune- checkpoint inhibitor (ICI) therapy and often co-presents with myositis and myocarditis. We present a series of six patients from a tertiary oncology center.MethodsWe reviewed The Christie Hospital database of immunotherapy-related toxicity from 2017–2020. Symptom severity was assessed using the MGFA classification.ResultsSix patients with ICI-related MG were identified. The median number of preceding immunotherapy doses was 2. Common initial presenting complaints were ptosis (100%) and diplopia (50%) with 2/6 patients showing severe (MGFA > II) symptoms. Five patients had concomitant myositis and myocarditis. AChR or MuSK autoantibodies were positive in three patients. Two patients required advanced respiratory support.All patients received urgent treatment with intravenous methylprednisolone and mycophenolate. Five also received intravenous immunoglobulin and a single patient was treated additionally with abatacept and rituximab. No patient died from MG-related complications. All were successfully discharged following the acute episode.DiscussionPrevious case series of ICI-related MG have reported high mortality rates, particularly in those with overlapping myositis/myocarditis. In our cohort we demonstrate good outcomes associated with early aggressive treatment with IVIG, IVMP, and mycophenolate. An agreed national treatment protocol or clinical discussion forum would be beneficial.jamweaver75@gmail.com17

Targeted Treatment for High-Risk Early-Stage Triple-Negative Breast Cancer: Spotlight on Pembrolizumab.

Triple-negative breast cancer (TNBC) is a biologically aggressive yet heterogeneous disease that disproportionately affects younger women and women of color compared to other breast cancer subtypes. The paucity of effective targeted therapies and the prevalence of chemotherapeutic resistance in high-risk, early-stage TNBC pose significant clinical challenges. Deeper insights into the genomic and immune landscape have revealed key features of TNBC, including intrinsic genomic instability, DNA repair deficiency, and potentially an immunogenic tumor microenvironment. These advances led to landmark trials with immune checkpoint inhibitors in the advanced-stage setting, which subsequently translated into immunotherapy-based clinical trials in the early-stage setting and recent promising results. Pembrolizumab, an anti-programmed death 1 (PD-1) monoclonal antibody, was investigated in combination with platinum-, taxane- and anthracycline-based neoadjuvant chemotherapy followed by adjuvant pembrolizumab monotherapy for patients with high-risk, early-stage TNBC in the randomized, double-blind, placebo-controlled phase 3 KEYNOTE-522 trial. In July 2021, the US Food and Drug Administration (FDA) granted approval for pembrolizumab based on marked improvement in pathologic complete response rate and 3-year event-free survival compared to neoadjuvant chemotherapy alone. This advance immediately altered the longstanding treatment paradigm. Here, we review the impact of pembrolizumab plus chemotherapy for the treatment of patients with high-risk, early-stage TNBC, and discuss immunotherapy-related toxicity considerations, key immunomodulatory biomarkers under active investigation, and remaining clinical questions for future research directions.

88 - Bone protection and Pneumocystis jirovecii prophylaxis in thoracic oncology patients receiving systemic steroids for immunotherapy-related toxicity

88 - Bone protection and Pneumocystis jirovecii prophylaxis in thoracic oncology patients receiving systemic steroids for immunotherapy-related toxicity

P40.07 Immunotherapy Toxicity in Lung Cancer & the Impact of Thoracic Radiation Therapy

Immunotherapy is increasingly utilized either alone or in combination with chemotherapy and/or radiation therapy (RT) with improved survival. Immunotherapy related toxicity can appear similar to radiation induced toxicity. The contribution of concurrent or sequential thoracic radiation to immunotherapy related cardiopulmonary toxicity is not well understood. Current literature suggests that combination of immunotherapy and thoracic radiation does not result in an increase in high-grade toxicities, however clinicians continue to approach this combination with caution. All patients that received immunotherapy for non-small cell lung cancer (NSCLC) between 2011 and 2020 were included in the analysis. The electronic medical records were used to collect demographic, treatment, and toxicity data. RTOG toxicity scale was used to grade pneumonitis and CTCAE was used for all other toxicities. The first course of radiation therapy was used for analysis if patients received more than one course. The relationship between thoracic RT and the incidence of cardiopulmonary toxicities was evaluated through pairwise comparisons using Barnard’s exact test of three groups including: patients who received thoracic RT ³ 45 Gy, thoracic RT < 45 Gy, and those who did not receive thoracic RT. To account for the three pairwise comparisons for each toxicity class, Bonferroni adjusted p-values were utilized. Additionally, the impact of RT type (thoracic vs. nonthoracic) and total dose (³ 45 Gy vs. < 45 Gy) over multiple courses of treatment was examined. The cause specific hazard ratios for toxicity outcomes were modeled using the Cox proportional hazards model, with time of treatment initiation designated as the time of origin. Candidate variables for inclusion included: receipt of any thoracic vs. non-thoracic RT, thoracic vs. nonthoracic RT received as most recent therapy relative to time of toxicity, total thoracic RT dose (³ 45 Gy or < 45 Gy), and total non-thoracic RT dose. The toxicity outcomes (all grade occurrences and grade 3-5 events) evaluated included cardiopulmonary toxicities of any type, pleural effusions, and pneumonitis events. 251 patients met the inclusion criteria and were included in the analysis. The majority of patients were locally advanced or metastatic at presentation; 33.5% stage III & 56.6% stage IV. RT was given in 83.3% of patients and 63.7% of patients received thoracic RT. An elevated risk of grade 3-5 pleural effusions was found in patients who received thoracic RT and cumulative dose < 45 Gy, however, the group that received ³ 45 Gy did not reveal an increased risk of grade 3-5 pleural effusions. Overall, the remaining candidate variables were not found to significantly impact the evaluated toxicity outcomes (p > 0.05). An increased risk of pleural effusions was found in patients who received a prior cumulative RT dose of <45 Gy. However, overall, the results of this large single-institution retrospective review do not show an association with thoracic RT and increased risk of cardiopulmonary toxicity in patients receiving immunotherapy for NSCLC. Further dosimetric analysis will be conducted to better characterize cardiopulmonary toxicity outcomes relative to radiation dose to the heart and lung.

Liver macrophages and neutrophils in immunotherapy-related toxicity

Liver macrophages and neutrophils in immunotherapy-related toxicity

Treatment-Related Toxicities During Anti-GD2 Immunotherapy in High-Risk Neuroblastoma Patients.

The introduction of immunotherapy using an anti-GD2 antibody (dinutuximab, ch14.18) has significantly improved survival rates for high-risk neuroblastoma patients. However, this improvement in survival is accompanied by a substantial immunotherapy-related toxicity burden. The primary objective of this study was to describe treatment-related toxicities during immunotherapy with dinutuximab, IL-2, GM-CSF, and isotretinoin. A retrospective, single center analysis of immunotherapy-related toxicities was performed in twenty-six consecutive high-risk neuroblastoma patients who received immunotherapy as maintenance therapy in the Princess Máxima Center (Utrecht, Netherlands). Toxicities were recorded and graded according to the CTCAE. Particular attention was drawn to pain and fever management and toxicities leading to dose modifications of dinutuximab and IL-2. Twenty-three patients (88%) completed all six courses of immunotherapy. Disease progression, isotretinoin-associated liver toxicity, and catheter-related infection in combination with peripheral neuropathy were reasons for immunotherapy discontinuation. The most common grade ≥3 toxicities for courses 1–5, respectively, were pain, catheter-related infections, and fever. In total, 310 grade ≥3 toxicities were recorded in 124 courses. Thirty-three grade 4 toxicities in 19/26 patients and no grade 5 toxicities (death) were seen. Fifty-nine percent of grade ≥3 toxicities were recorded in the two courses with IL-2. Catheter-related bloodstream infections were identified in 81% of patients. Four of these episodes led to intensive care admission followed by full recovery (grade 4).

Immunotherapy-related toxicity in lung cancer: clinical characteristics and managing strategy.

Immunotherapy-related toxicity in lung cancer: clinical characteristics and managing strategy.

Synoptic reporting in lung cancers using Lung Cancer Reporting and Data System (LC-RADS): The road ahead for standardization of imaging in lung cancer staging

Words are the most important and sometimes the only medium of communication between a radiologist and a treating physician. The concept of structured reporting in radiology was well received in the face of growing concerns to overcome the limitations of unstructured reporting such as interobserver variations, errors in communication, and lack of standardization of reporting that primarily affect the patients who seek health care away from their diagnostic centers. With the introduction of synoptic reporting in radiology, it is now possible to standardize the reporting of diseases in a more comprehensive and less time-consuming manner, thus magnifying the impact of a radiological report in the further management of the disease under analysis. We aim to develop a standardized synoptic reporting template for lung cancers that would comprise and collate all the required computed tomography (CT) findings and demographic details of the patients. This will help the treating physicians and surgeons to plan the further course of disease management. It will also help to standardize the follow-up CT scans performed for the patients post any given treatment regimen with special reference to the likely complications caused by a particular treatment, such as radiation-related lung injury, immunotherapy-related toxicity, and surgical complications requiring urgent interventions.

Real-world experience with elective discontinuation of PD-1 inhibitors at 1 year in patients with metastatic melanoma

BackgroundRandomized trials evaluating programmed cell death protein 1 (PD-1) inhibitors in metastatic melanoma either permitted treatment for 2 years (pembrolizumab) or more (nivolumab). The optimal duration of therapy is currently...

Molecular biomarkers to predict response to immunotherapy in endometrial cancer patients enrolled on the profile related evidence determining individualized cancer therapy (PREDICT) trial (NCT02478931) at the UC San Diego Moores Cancer Center

Objective: A minority of endometrial cancer patients have robust and durable responses to immunotherapy; however, biomarkers are urgently needed to select which patients will benefit and to spare others from immunotherapy-related toxicity.