Spotlighting rising researcher Jiahui Li: advancing cancer treatment with HPMA-based therapeutics: innovations in receptor crosslinking, targeted delivery, and chemo-immunotherapy

The understanding of localized radiation therapy's immunostimulatory properties combined with its well-known effects on the cell cycle and insights into the immunomodulation mechanisms that occur at the molecular and cellular levels has changed our traditional view of the anticancer effects of ionizing radiation. The potential interactions between the tumor's immune system and radiation therapy have revealed that local radiation has the ability to induce systemic antitumor responses in patients with advanced cancers. The recognition of systemic antitumor effects of radiation therapy has allowed investigators to begin uncovering the integral players in these pathways. Parallel to this, there has been progress in understanding how tumor immunology leads to the development of novel immunotherapies using immune checkpoint blockade therapies in the treatment of advanced cancers. To date there has been limited success in this benefiting only a small fraction of patients. The concept of priming the body's immune system by radiation to make less responsive tumors more responsive to immunotherapy provides an opportunity to explore the use of the combination of radiation therapy and immunotherapy for the treatment of advanced non-small cell lung cancer and other cancers. This article provides an overview of the current state of knowledge of the clinical experience using radiation therapy in combination with immune therapy and discusses the rationale for integrating these 2 modalities in the treatment of advanced non-small cell lung cancer. Available data supports the use of radiation therapy in combination with immunotherapy to achieve improved local and systemic tumor control. Evidence from the early clinical trials has shown that using radiation therapy and immune checkpoint blockade therapies together produces a greater clinical effect than using either modality alone. To maximize the clinical benefit and successful integration of these two modalities as well as optimizing radiation therapy dosing and its schedule, improvement in its field design and the development of reliable predictors of clinical tumor response needs to be established.

Twenty-five years of treating advanced NSCLC: what have we achieved?

ATP in the Treatment of Advanced Cancer

Disclosure: D. Chen: None. M. Banerjee: None. T. Xu: None. F.P. Worden: None. M.R. Haymart: None. Background. Since 2011, the United States Food and Drug Administration (FDA) has approved eight small-molecule kinase inhibitors (SMKIs) for the treatment of advanced thyroid cancer (i.e., radioiodine-refractory metastatic differentiated thyroid cancer, metastatic medullary thyroid cancer, and anaplastic thyroid cancer). The National Comprehensive Cancer Network (NCCN) clinical practice guidelines recommend use of 15 SMKIs, of which eight are FDA-approved and seven are commercially available, for the treatment of advanced thyroid cancer. However, little is known about how these medications are used in the real-world setting for treatment of patients with advanced thyroid cancer. Methods. This descriptive study used data from Optum Clinformatics Data Mart, a de-identified commercial claims database of a large national health insurance provider. We identified patients with thyroid cancer who had prescription claims for at least one of the 15 SMKIs of interest (axitinib, cabozantinib, dabrafenib, entrectinib, everolimus, larotrectinib, lenvatinib, pazopanib, pralsetinib, selpercatinib, sorafenib, sunitinib, trametinib, vandetanib, and vemurafenib). Lines of therapy were defined by the date of SMKI claims. We describe changes in usage patterns over time with a focus on the demographics of patients who were newly initiated on treatment of advanced thyroid cancer, and on the medications used for each line of therapy. Results. Between 2013-2021, 886 patients were treated for advanced thyroid cancer with at least one of the 15 SMKIs of interest. Median age was 65.1 years. Most patients were female (54.6%), non-Hispanic White (62.1%), and had supplementary Medicare insurance (60.6%). Between 2013 and 2016, there was an increase in the proportion of Hispanic patients and a corresponding decrease in the proportion of non-Hispanic White patients treated for advanced thyroid cancer. Although most patients were initiated on an FDA-approved SMKI as first line therapy, 23.1% (N=205) were initiated on a commercially available SMKI. Sorafenib was the most prescribed first-line therapy in 2013 (24.4%) and 2014 (48.3%). Lenvatinib was the most prescribed first-line therapy between 2015-2021 when prescriptions for lenvatinib constituted 38.3-55.6% of all SMKIs prescribed for the treatment of advanced thyroid cancer. Between 2017-2021, a minority of patients were treated with up to a fifth line of therapy although the majority (81.8%) were treated with only a first line agent. Conclusions. Since 2015 when lenvatinib was approved by the FDA for treatment of advanced differentiated thyroid cancer, it has become the most commonly prescribed SMKI for treatment of advanced thyroid cancer. However, variation exists in which SMKIs are used to treat patients with advanced thyroid cancer, with almost one-quarter of patients initiated on commercially available SMKIs. Presentation Date: Saturday, June 17, 2023

Chemotherapy is indispensable for the treatment of advanced biliary tract cancer. Recently, reports regarding first-line chemotherapy have increased, and first-line chemotherapy treatment has become gradually more sophisticated. Gemcitabine and cisplatin combination therapy (or gemcitabine and oxaliplatin combination therapy) have become the standard of care for advanced biliary tract cancer. Oral fluoropyrimidines have also been shown to have good antitumor effects. Gemcitabine, platinum compounds, and oral fluoropyrimidines are now considered key drugs for the treatment of advanced biliary tract cancer. Several clinical trials using molecular targeted agents are also ongoing. Combination therapy using cytotoxic agents and molecular-targeted agents has been evaluated widely. However, reports regarding second-line chemotherapy remain limited, and it has not yet been clarified whether second-line chemotherapy can improve the prognosis of advanced biliary tract cancer. Thus, there is an urgent need to establish second-line standard chemotherapy treatment for advanced biliary tract cancer. Several problems exist when assessing the results of previous reports concerning advanced biliary tract cancer. In the present review, the current status of the treatment of advanced biliary tract cancer is summarized, and several associated problems are indicated. These problems should be solved to achieve more sophisticated treatment of advanced biliary tract cancer.

Breast cancer is the most common malignant tumor among women all over the world. In 2022, there were about 357,161 new cases and 74,986 deaths of breast cancer in Chinese female. Of the new cases of breast cancer each year, about 5% to 10% of patients have distant metastasis at the time of diagnosis. Of the early-stage patients, about 20%~30% developed into advanced breast cancer eventually. Although advanced breast cancer is difficult to cure at present, we can alleviate the clinical symptoms of patients, improve their quality of life and further prolong their survival time by applying new therapeutic drugs and optimizing treatment models, to achieve the purpose of long-term survival with tumor. To better guide clinical practice, the Chinese expert group, based on the latest research progress in breast cancer, has analyzed, discussed, and updated the relevant research data on the basis of "Guidelines for clinical diagnosis and treatment of advanced breast cancer in China (2022 edition)" to form the "Guidelines for clinical diagnosis and treatment of advanced breast cancer in China (2024 edition)" . The updated guideline incorporates the new evidence of high-quality evidence-based medicine, new concepts in molecular pathological detection, new treatment strategies, new progress in precision medicine, and adverse events of new therapeutic drugs. At the same time, the updated guideline emphasizes multidisciplinary collaboration and pays attention to patient-reported outcomes. The "Guidelines for clinical diagnosis and treatment of advanced breast cancer in China (2024 edition)" aims to provide clinicians with recommendations for the diagnosis and treatment of advanced breast cancer in China, thereby improving patient outcomes and quality of life.

BackgroundUnresectable advanced or recurrent gastric cancer patients have a poor prognosis. PD-1 monotherapy regimen and PD-1 combined chemotherapy regimen have become the standard third- and first-line treatment for advanced gastric cancer, respectively. However, the status of immune checkpoint inhibitors in the second-line treatment for advanced gastric cancer has not been established. The combination of chemotherapy and anti-PD-1 antibody has been demonstrated to have a synergistic effect. In this study, we aimed to evaluate the efficacy and safety of sintilimab combined with nab-paclitaxel in the second-line treatment for advanced gastric cancer (GC)/gastroesophageal junction (GEJ) cancer patients.Patients and MethodsWe retrospectively analyzed patients with advanced GC/GEJ cancer that progressed after first-line systemic therapies with sintilimab combined with nab-paclitaxel from April 1, 2019 to December 31, 2021. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety.ResultsThirty-nine patients were enrolled and eligible for response assessment. Complete response (CR) was not observed, 15 patients achieved partial response (PR), 16 patients had stable disease (SD) and 9 patients had progressive disease (PD). The ORR and DCR were 15 (38.5%) and 31 (79.5%), respectively. Median PFS was 5.4 months (95%CI: 3.072-7.728). PFSs between different subgroups were analyzed. The results showed that gender, age, Human epidermal growth factor receptors 2 (HER2) status, PD-L1 expression, primary tumor site and chemotherapy cycles had no significant effect on PFS. Most of the adverse events (AEs) were of grade 1-2 and manageable. The common treatment-related adverse events of grade 3 or 4 included anemia (12.8%), neutropenia (12.8%), leukopenia (10.3%), hand-foot syndrome (7.7%), thrombocytopenia (7.7%). The potential immune-related adverse events (irAEs) were grade 1 pneumonia (1 pts [2.6%]) and grade 4 hepatitis (1 pts [2.6%]). There were no treatment-related deaths.ConclusionThese results indicate that sintilimab combined with nab-paclitaxel exhibits good anti-tumor activity and an acceptable safety profile as a second-line treatment for advanced or metastatic gastric cancer. These results warrant further investigation and evaluation to identify patients who can benefit more from the combined treatment strategy.

New Horizons in Chemotherapy: Platforms for Combinations in First-Line Advanced Non-small Cell Lung Cancer

Background: Little is known about the psychosocial care experience of Muslims who are in treatment of advanced cancer in non-Muslim majority settings. Aim: To describe the experience of Muslims who are in treatment of advanced cancer in a non-Muslim majority setting and to identify beliefs and practices for culturally congruent psychosocial care. Methods: This cross-sectional study, which is in progress, uses a semistructured interview guide and self-report questionnaires with Muslim patients ≥ 21 years who are in treatment of stage III or IV cancer at an academic cancer center in the northeast of the United States. Analysis of interviews is by grounded theory and of questionnaires by frequencies, percentages, and measures of central tendency and dispersion for quality of life: Functional Assessment of Cancer Therapy-General (FACT-G; range 0-108) with subscales: Physical Well-Being (PWB [range 0-28]), Social Well-Being (SWB [range 0-28]), Emotional Well-Being (EWB [range 0-24]), and Functional Well-Being (FWB [range 0-28]; higher scores reflect better quality of life Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp [range 0-48]), with subscales: peace (range 0-16), meaning (range 0-16), and faith (range 0-16); higher scores reflect better spiritual well-being. Distress Thermometer (DT; 0 = no distress, 10 = worst distress). Hospital Anxiety and Depression Scale (HADS), with subscale: anxiety (0-21) and depression (0-21); higher scores reflect worse condition. Results: Eleven (female, n=5 [45.5%]) Muslim patients from 10 countries of origin with a mean age of 55.2 (±10.9) years who were in treatment of breast, colorectal, gastric, lung, ovarian, prostate, melanoma and lymphoma cancers (Stage 4, n=8 [72.7%]) have been interviewed to date. Mean scores were: FACT-G 85.6 (±17.9) (PWB 22.3 [±5.1], SWB 23.8 [±3.8], EWB 18.6 [±4.5], FWB 20.7 [±6.7]; FACIT-Sp 123.8 (±24.6) (peace 11.6 [±4.5], meaning 13.7 [±3.1], faith 12.9 [±3.8]), DT 2.13 (SD 2.58); HADS anxiety 3.9 (±3.2) and depression 3.8 (±3.7). Four universal themes emerged: (1) Faithful Muslims must seek and submit to treatment. (2) Spiritual practices (prayer and other traditional healing practices) are sources of meaning. (3) Psychosocial care in a non-Muslim majority setting is often presented in ways incongruent with Muslims' beliefs and practices. (4) Psychosocial care would be acceptable if congruent with Muslims' beliefs and practices. Conclusion: Presenting psychosocial care as part of routine cancer treatment and, in non-Muslim majority settings, delivering psychosocial care that is culturally congruent with Islamic beliefs and practices, may increase the acceptability of psychosocial care among Muslims who are in treatment of advanced cancer.

Surveys indicate considerable variation regarding the provision of cancer treatment at the end of life. The variation cannot be fully explained by differences concerning the clinical situation or patients' preferences. The aim of this qualitative study was to explore medical oncologists' experiences with advanced cancer, as well as their views of the relevance of medical and nonmedical criteria for decisions about limiting treatment. Qualitative in-depth interviews were conducted with physicians working in medical oncology in tertiary care hospitals or district general hospitals in England. Purposive sampling and qualitative analysis were performed. Physicians reported that a number of nonmedical factors influence professional decisions about the offering or limiting of cancer treatment in advanced cancer in addition to medical criteria. Physicians' individual judgments about the benefit of treatment, as well as the amount of their clinical experience, were cited as such factors. In addition, the physicians' perceptions of the patient's age and life circumstances were reported to influence their treatment decisions. Multiprofessional team discussions and the systematic collection of relevant clinical data regarding the outcomes of different treatment approaches in advanced cancer were suggested as strategies to improve the quality of treatment decisions. The findings of this study provide explanations for the variation in treatment in advanced cancer. Making value judgments explicit and gathering more appropriate clinical data on the outcomes of treatment near the end of life are prerequisites for improved ethical and evidence-based treatment decisions in advanced cancer.

This study assessed the use of intermediate endpoints in the economic evaluation of new treatments for advanced cancer and the methodological approaches adopted when overall survival (OS) data are unavailable or of limited use. A systematic literature review was conducted to identify economic evaluations of treatments for advanced cancer published between 2003 and 2013. Cost-effectiveness and cost-utility analyses expressed in cost per life-year gained and cost per quality-adjusted life-year using an intermediate endpoint as an outcome measure were eligible. Characteristics of selected studies were extracted and comprised population, treatment of interest, comparator, line of treatment, study perspective, and time horizon. Use of intermediate endpoints and methods adopted when OS data were lacking were analyzed. In total, 7219 studies were identified and 100 fulfilled the eligibility criteria. Intermediate endpoints mostly used were progression-free survival and time to progression, accounting for 92% of included studies. OS data were unavailable for analysis in nearly 25% of economic evaluations. In the absence of OS data, studies most commonly assumed an equal risk of death for all treatment groups. Other methods included use of indirect comparison based on numerous assumptions, use of a proxy for OS, consultation with clinical experts, and use of published external information from different treatment settings. Intermediate endpoints are widely used in the economic evaluation of new treatments for advanced cancer in order to estimate OS. Currently, different methods are used in the absence of suitable OS data and the choice of an appropriate method depends on many factors including the data availability.

Background: The growing group of people with advanced cancer and systemic treatment faces psychosocial challenges, including fear of progression (FoP). This study aimed to identify features that characterize FoP in people with advanced cancer and systemic treatment. Methods: An exhaustive list of possible FoP characteristics was generated based on literature, patient-reported outcome measures on FCR and FoP, interview data, and clinical expertise. Members of the International Psycho-Oncology Society (IPOS) Special Interest Group FORwards with expertise in FoP in people with advanced cancer and systemic treatment were invited to score features in a 2-round modified Delphi study. Features were scored on a 5-point Likert scale indicating their importance as a feature of FoP and reached consensus to be included or excluded if more than two-thirds applied the same score. A list of agreed features of FoP was generated. Results: A total of 21 participants completed both Delphi rounds, including psychologists, researchers, nurses, and one psychiatrist. Of the 55 rated features, 31 features reached consensus to be features of FoP in advanced cancer, including items on fear, uncertainty, worry, loss, hopelessness, and interference with daily life. Conclusions: Reaching expert consensus is a critical first step in identifying features of FoP in people with advanced cancer and systemic treatment, highlighting uncertainty and fear of death as unique challenges. Identifying features of FoP in advanced cancer is essential to guide future psycho-oncological research and clinical practice to improve psychosocial guidance with FoP for the growing group of people with advanced cancer and systemic treatment.

Objective To systematically evaluate the efficacy of the lienal polypeptide injection combined with chemotherapy or radiotherapy on the short-term efficacy, Karnofsky score, immune function and adverse reactions in treatment of various cancers. Methods The databases of PubMed, Embase, Cochrane Library, CNKI, Wanfang and VIP were retrieved from database establishing time to January 2017, and the randomized controlled trials (RCT) about lienal polypeptide injection combined with radiotherapy or chemotherapy in the treatment of advanced cancer were collected. The quality assessment was conducted and eligible trials were included in the Meta-analysis. Results A total of 23 articles were included, involving 1 658 patients. The patients were divided into treatment group (lienal polypeptide injection combined with chemotherapy or radiotherapy, 842 cases) and control group (chemotherapy or radiotherapy alone, 816 cases). Results of Meta-analysis showed that the short-term effective rate (RR= 1.20, 95% CI 1.07-1.33, P= 0.001), the improvement rate of Karnofsky score (RR= 1.77, 95% CI 1.43-2.19, P 0.05). Conclusion Lienal polypeptide injection combined with radiotherapy or chemotherapy is superior to conventional radiotherapy or chemotherapy alone in the treatment of cancer, which can improve the quality of life of patients with tumors, reduce the incidence of nausea and vomiting and bone marrow suppression induced by the treatment. Key words: Neoplasms; Lienal polypeptide injection; Neoadjuvant therapy; Meta-analysis

BackgroundThe MONARCH 3 trial has demonstrated that Anastrozole combined with Abemaciclib is safe and effective for the treatment of postmenopausal hormone receptor-positive advanced breast cancer. However, its cost-effectiveness for long-term use has not been investigated yet. This study aims to evaluate the cost-effectiveness of Anastrozole combined with Abemaciclib versus Anastrozole used alone for patients in China.MethodsBased on MONARCH 3 trial data, we constructed a Markov model using Treeage Pro 2022 software. The model cycle was set at 1 month over a period of 20- year time horizon, and the annual discount rate was set at 5%. The cost-utility analysis was used to assess the cost-effectiveness of Anastrozole combined with Abemaciclib for the treatment of postmenopausal hormone receptor-positive advanced breast cancer. The output indexes of the model were cost and quality-adjusted life year (QALY), and the model evaluation index was incremental cost-effectiveness ratio (ICER). The willingness to pay (WTP) threshold was set at 3 times the per-capita gross domestic product (GDP) of China in 2023 (¥268,074/QALY). Meanwhile, one-way sensitivity analysis and probabilistic sensitivity analysis were used to explore the uncertainties of the model and parameters.ResultsAnastrozole combined with Abemaciclib provided more health benefits than Anastrozole used alone, however, the total cost was higher. The incremental utility and incremental cost were 0.01 QALYs and ¥1075.51, respectively. And the ICER of the two regimens was ¥93,940.83/QALY, which was less than 3 times the per-capita GDP of China in 2023 (¥268,074). The results of the sensitivity analysis attested that the study results were robust.ConclusionsAnastrozole combined with Abemaciclib is more cost-effective than Anastrozole used alone for the treatment of postmenopausal hormone receptor-positive advanced breast cancer.

Systemic treatment of advanced colorectal cancer: Incorporating new agents into the therapeutic strategy