scholarly journals Utilization of target lesion heterogeneity for treatment efficacy assessment in late stage lung cancer

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0252041
Author(s):  
Dung-Tsa Chen ◽  
Wenyaw Chan ◽  
Zachary J. Thompson ◽  
Ram Thapa ◽  
Amer A. Beg ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Unmet Need ◽  
Target Lesion ◽  
Small Sample ◽  
Study Cohort ◽  
Mixed Effect ◽  
Mixed Response ◽  
Response Classification

Rationale Recent studies have discovered several unique tumor response subgroups outside of response classification by Response Evaluation Criteria for Solid Tumors (RECIST), such as mixed response and oligometastasis. These subtypes have a distinctive property, lesion heterogeneity defined as diversity of tumor growth profiles in RECIST target lesions. Furthermore, many cancer clinical trials have been activated to evaluate various treatment options for heterogeneity-related subgroups (e.g., 29 trials so far listed in clinicaltrials.gov for cancer patients with oligometastasis). Some of the trials have shown survival benefit by tailored treatment strategies. This evidence presents the unmet need to incorporate lesion heterogeneity to improve RECIST response classification. Method An approach for Lesion Heterogeneity Classification (LeHeC) was developed using a contemporary statistical approach to assess target lesion variation, characterize patient treatment response, and translate informative evidence to improving treatment strategy. A mixed effect linear model was used to determine lesion heterogeneity. Further analysis was conducted to classify various types of lesion variation and incorporate with RECIST to enhance response classification. A study cohort of 110 target lesions from 36 lung cancer patients was used for evaluation. Results Due to small sample size issue, the result was exploratory in nature. By analyzing RECIST target lesion data, the LeHeC approach detected a high prevalence (n = 21; 58%) of lesion heterogeneity. Subgroup classification revealed several informative distinct subsets in a descending order of lesion heterogeneity: mix of progression and regression (n = 7), mix of progression and stability (n = 9), mix of regression and stability (n = 5), and non-heterogeneity (n = 15). Evaluation for association of lesion heterogeneity and RECIST best response classification showed lesion heterogeneity commonly occurred in each response group (stable disease: 16/27; 59%; partial response: 3/5; 60%; progression disease: 2/4; 50%). Survival analysis showed a differential trend of overall survival between heterogeneity and non-heterogeneity in RECIST response groups. Conclusion This is the first study to evaluate lesion heterogeneity, an underappreciated metric, for RECIST application in oncology clinical trials. Results indicated lesion heterogeneity is not an uncommon event. The LeHeC approach could enhance RECIST response classification by utilizing granular lesion level discovery of heterogeneity.

Improving hematology/oncology clinical research recruitment via universal prescreening: The VA Connecticut (VACT) Cancer Center experience.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 79-79
Author(s):  
Jenny Jing Xiang ◽  
Alicia Roy ◽  
Christine Summers ◽  
Monica Delvy ◽  
Jessica Lee O'Donovan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Clinical Research ◽  
Cancer Patients ◽  
Cancer Center ◽  
Cancer Type ◽  
Eligibility Criteria ◽  
Research Recruitment ◽  
Lung Cancer Patients ◽  
Study Enrollment

79 Background: Patient-trial matching is a critical step in clinical research recruitment that requires extensive review of clinical data and trial requirements. Prescreening, defined as identifying potentially eligible patients using select eligibility criteria, may streamline the process and increase study enrollment. We describe the real-world experience of implementing a standardized, universal clinical research prescreening protocol within a VA cancer center and its impact on research enrollment. Methods: An IRB approved prescreening protocol was implemented at the VACT Cancer Center in March 2017. All patients with a suspected or confirmed diagnosis of cancer are identified through tumor boards, oncology consults, and clinic lists. Research coordinators perform chart review and manually enter patient demographics, cancer type and stage, and treatment history into a REDCap (Research Electronic Data Capture) database. All clinical trials and their eligibility criteria are also entered into REDCap and updated regularly. REDCap generates real time lists of potential research studies for each patient based on his/her recorded data. The primary oncologist is alerted to a patient’s potential eligibility prior to upcoming clinic visits and thus can plan to discuss clinical research enrollment as appropriate. Results: From March 2017 to December 2020, a total of 2548 unique patients were prescreened into REDCAP. The mean age was 71.5 years, 97.5% were male, and 15.5% were African American. 32.57 % patients had genitourinary cancer, 17.15% had lung cancer, and 46.15% were undergoing malignancy workup. 1412 patients were potentially eligible after prescreening and 556 patients were ultimately enrolled in studies. The number of patients enrolled on therapeutic clinical trials increased after the implementation of the prescreening protocol (35 in 2017, 64 in 2018, 78 in 2019, and 55 in 2020 despite the COVID19 pandemic). Biorepository study enrollment increased from 8 in 2019 to 15 in 2020. The prescreening protocol also enabled 200 patients to be enrolled onto a lung nodule liquid biopsy study from 2017 to 2019. Our prescreening process captured 98.57% of lung cancer patients entered into the cancer registry during the same time period. Conclusions: Universal prescreening streamlined research recruitment operations and was associated with yearly increases in clinical research enrollment at a VA cancer center. Our protocol identified most new lung cancer patients, suggesting that, at least for this malignancy, potential study patients were not missed. The protocol was integral in our program becoming the top accruing VA site for NCI’s National Clinical Trial Network (NCTN) studies since 2019.

scholarly journals Combining Radiotherapy and Immunotherapy in Lung Cancer: Can We Expect Limitations Due to Altered Normal Tissue Toxicity?

2018 ◽  
Vol 20 (1) ◽  
pp. 24 ◽  
Author(s):  
Florian Wirsdörfer ◽  
Simone de Leve ◽  
Verena Jendrossek
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Cancer Therapy ◽  
Cancer Patients ◽  
Cancer Biology ◽  
Normal Tissue ◽  
Radiation Treatment ◽  
Current Knowledge ◽  
Immune Checkpoint Blockade ◽  
Normal Tissue Toxicity

In recent decades, technical advances in surgery and radiotherapy, as well as breakthroughs in the knowledge on cancer biology, have helped to substantially improve the standard of cancer care with respect to overall response rates, progression-free survival, and the quality of life of cancer patients. In this context, immunotherapy is thought to have revolutionized the standard of care for cancer patients in the long term. For example, immunotherapy approaches such as immune checkpoint blockade are currently increasingly being used in cancer treatment, either alone or in combination with chemotherapy or radiotherapy, and there is hope from the first clinical trials that the appropriate integration of immunotherapy into standard care will raise the success rates of cancer therapy to a new level. Nevertheless, successful cancer therapy remains a major challenge, particularly in tumors with either pronounced resistance to chemotherapy and radiation treatment, a high risk of normal tissue complications, or both, as in lung cancer. Chemotherapy, radiotherapy and immunotherapy have the capacity to evoke adverse effects in normal tissues when administered alone. However, therapy concepts are usually highly complex, and it is still not clear if combining immunotherapy with radio(chemo)therapy will increase the risk of normal tissue complications, in particular since normal tissue toxicity induced by chemotherapy and radiotherapy can involve immunologic processes. Unfortunately, no reliable biomarkers are available so far that are suited to predict the unique normal tissue sensitivity of a given patient to a given treatment. Consequently, clinical trials combining radiotherapy and immunotherapy are attracting major attention, not only regarding efficacy, but also with regard to safety. In the present review, we summarize the current knowledge of radiation-induced and immunotherapy-induced effects in tumor and normal tissue of the lung, and discuss the potential limitations of combined radio-immunotherapy in lung cancer with a focus on the suspected risk for enhanced acute and chronic normal tissue toxicity.

scholarly journals PET/CT and the Response to Immunotherapy in Lung Cancer

2020 ◽  
Vol 13 (3) ◽  
pp. 177-184 ◽  
Author(s):  
Laura Evangelista ◽  
Matteo Sepulcri ◽  
Giulia Pasello
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Fdg Pet ◽  
Response To Therapy ◽  
Prediction Of Response ◽  
Lung Cancer Patients ◽  
Pet Ct ◽  
Fdg Pet Ct

Objective: In recent years, the introduction of immune checkpoint inhibitors has significantly changed the outcome of patients affected by lung cancer and cutaneous melanoma. Although the clinical advantages, the selection of patients and the evaluation of response to immunotherapy remain unclear, the immune-related Response Evaluation Criteria in Solid Tumor (irRECIST) was proposed as an update of the RECIST criteria for the assessment of response to immunotherapy. However, morphological images cannot predict early response to therapy that represents a challenge in clinical practice. 18F-FDG PET/CT before and after immunotherapy has an indeterminate role, demonstrating ambiguous results due to inflammatory effects secondary to activation of the immune system. The aim of the present review was to analyze the role of PET/CT as a guide for immunotherapy, by analyzing the current status and future perspectives. Methods: A literature search was conducted in order to select all papers that discussed the role of PET/CT with FDG or other tracers in the evaluation or prediction of response to immunotherapy in lung cancer patients. Results: Many papers are now available. Many clinical trials have demonstrated the efficacy of immunotherapy in lung cancer patients. FDG PET/CT can be used for the prediction of response to immunotherapy, while its utility for the evaluation of response is not still clearly reported. Moreover, the standardization of FDG PET/CT interpretation is missing and different criteria, such as information, have been investigated until now. Conclusions: The utility of FDG PET/CT for patients with lung cancer undergoing immunotherapies is still preliminary and not well addressed. New agents for PET are promising, but large clinical trials are mandatory.

scholarly journals Objective quantitation of EGFR protein levels using Quantitative Dot Blot (QDB) method for prognosis of gastric cancer patients

2021 ◽  
Author(s):  
Lei Xin ◽  
Fangrong Tang ◽  
Bo Song ◽  
Maozhou Yang ◽  
Jiandi Zhang
Keyword(s):  
Gastric Cancer ◽  
Lung Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Cox Regression ◽  
Dot Blot ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Gastric Cancer Patients

Background: One causing factor underlying failures of several clinical trials of anti-EGFR therapies is the lack of effective method to select patients overexpressing EGFR protein. Quantitative Dot Blot method (QDB) is proposed here to measure EGFR protein levels objectively and quantitatively. Its feasibility was evaluated for prognosis of overall survival (OS) of gastric cancer patients. Methods: FFPE slices of 2X5 microM from gastric and Lung cancer specimens were used to extract total tissue lysates for QDB measurement. Absolutely quantitated EGFR protein levels were used for Kaplan-Meier Overall Survival (OS) analysis of gastric cancer patients. Results: EGFR protein levels ranged from 0 to 772 pmole/g for gastric cancer specimens (n=246), and from 0 to 2695 pmole/g for lung cancer patients (n=81). Poor correlation was observed between quantitated EGFR levels and IHC scores with r=0.018, p=0.786 from Spearman correlation analysis. EGFR was identified as an independent negative prognostic biomarker for gastric patients only through absolute quantitation, with HR at 2.29 (95%CI:1.23-4.26, p=0.0089) from multivariate cox regression OS analysis. A cutoff of 207.7 pmole/g was proposed to stratify gastric cancer patients, with 5-year survival probability at 37% for those whose EGFR levels were above the cutoff, and at 64% those below the cutoff based on Kaplan-Meier OS analysis. p=0.0057 from Log Rank test. Conclusion: A QDB-based assay was developed for both gastric and Lung cancer specimens to measure EGFR protein levels absolutely, quantitatively and objectively. This assay should facilitate clinical trials aiming to evaluate anti-EGFR therapies retrospectively and prospectively.

Immunotherapy in Advanced Non-Small Cell Lung Cancer

2020 ◽  
Vol 41 (03) ◽  
pp. 400-408 ◽  
Author(s):  
Joy Huang ◽  
Karen L. Reckamp
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Advanced Lung Cancer ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Programmed Death

AbstractTraditionally, lung cancer has been treated as an immune-resistant disease with platinum-based chemotherapy serving as the first-line treatment for metastatic disease. The efficacy of immunotherapy has been established for patients with advanced lung cancer in clinical trials, and it has since become the standard of care for patients without targetable mutations, with or without chemotherapy. Previously, lung cancer patients experienced limited responses to immune-based therapy. As clinical trials continued to explore immunotherapy options with checkpoint inhibitors, results showed that immune therapies can create durable responses with manageable toxicities. Patients with advanced non-small cell lung cancer (NSCLC) can experience improved survival when administered immunotherapy over chemotherapy. The first successful immunotherapy treatments developed exploit programmed death 1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), immune checkpoint pathways. Combination therapies of PD-1/PD-L1 inhibitors and chemotherapy or PD-1/PD-L1 and CTLA-4 checkpoint pathway inhibitors have also demonstrated improved outcomes for patients with NSCLC. Combination therapy with PD-1 or PD-L1 therapy and chemotherapy has shown benefit for small cell lung cancer patients as well. As immunotherapy changes the treatment paradigm of lung cancer, researchers continue to investigate different combinations, timing, duration, and biomarkers to better understand and improve the efficacy of immune-based therapy for patients with lung cancer.

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