American Society Of Clinical Oncology Research Articles

Salivary Gland Tumors: Limitations of International Guidelines and Status of the planned AWMF-S3-Guideline

Primary salivary gland carcinomas are not among the common head and neck tumors. They are characterized by manifold different histological types. Clinically, malignant tumors often cannot be distinguished from benign tumors, so that in these cases malignancy is only established by histopathological diagnosis. These are all reasons why there are relatively few clinical trials on the diagnosis, therapy and follow-up of these tumors. This in turn has the consequence that often only recommendations with limited evidence can be made in clinical guidelines. The most important international guidelines are the National Comprehensive Cancer Network (NCCN) guideline of 2023, the American Society of Clinical Oncology (ASCO) guideline of 2021, the European Society for Medical Oncology (ESMO) guideline of 2022 and still the British National Multidisciplinary guideline of 2016. These 4 international guidelines with their strengths and limitations are presented and commented here. Against this background, the development of a first German S3 clinical guideline on salivary gland tumors is important and expected to be completed in 2023. For the first time in the German guideline program on oncology, benign and malignant tumors are presented together in order to comprehensively do justice to the special features of salivary gland tumors.

Immunotherapy for advanced non-small cell lung cancer with negative programmed death-ligand 1 expression: a literature review.

Lung cancer, mainly non-small cell lung cancer (NSCLC), is a serious threat to human life. In particular, the prognosis for advanced patients is poor, with the 5-year survival rate being exceedingly low. In recent years, immune checkpoint inhibition has changed the pattern of the treatment of a variety of cancers, including lung cancer; however, not all patients can benefit from immunotherapy, and thus finding the right biomarkers is particularly important for guiding precise treatment. Programmed death-ligand 1 (PD-L1) expression is one of the most valuable biomarkers for predicting the efficacy of lung cancer immunotherapy. Several studies have confirmed that patients with high PD-L1 expression are more likely to benefit from immunotherapy, but there is a high proportion of people with negative PD-L1 expression constituting a patient population that cannot be ignored. This article reviews the distribution of PD-L1 expression, the methods for evaluating PD-L1, and the effectiveness of immunotherapy for advanced NSCLC with negative PD-L1 expression. We performed a literature review to identify relevant data published until September 2022. In order to organize related information, we searched for literature in PubMed; abstracts and reports published in the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the World Conference on Lung Cancer (WCLC), and other congresses; and clinical trial information registered on ClinicalTrials.gov. Information on the distribution of PD-L1 expression, detection of PD-L1, and immunotherapy efficacy for NSCLC with negative PD-L1 expression was collated and reviewed. The incidence of PD-L1 expression in patients with stage IIIB/IV NSCLC is similar in all regions of the world, but PD-L1 expression level is associated with certain clinicopathological features. The expression of PD-L1 can be evaluated by various detecting methods. Some immunotherapy regimens have better efficacy than traditional chemotherapy in patients with negative PD-L1 expression. Patients with NSCLC and negative PD-L1 expression can receive better survival benefits under some immunotherapy types, and these may represent a better treatment option for this relatively small patient population.

Immune Checkpoint Inhibitor-Associated Myocarditis: A Literature Review.

Recently in the field of oncology, immune checkpoint inhibitors (ICI) are being increasingly utilized both in clinical trials and in clinical practice. It is a form of biological therapy that targets tumors by activating the immune system, which in turn eliminates proliferating cancer cells. These have numerous immune-related adverse events (irAEs), one of which is myocarditis, which has high rates of mortality. This article was a narrative review of myocarditis related to ICI use. Studies from the PubMed, Cochrane, and American Society of Clinical Oncology (ASCO) databases were used in writing this review. The databases were searched for original publications for adverse effects related to ICI use and myocarditis specifically.There are numerous published instances of cancer immunotherapy causing myocarditis. ICI therapy has numerous benefits, as it upregulates the immune system to target cancer cells, utilizing the body's own defense mechanisms to target proliferating cells. Myocarditis is a serious side effect, however. Therefore, on balance, these monotherapies are worth using. While this literature review primarily identifies cross-reaction as the main mechanism of myocarditis, there are other possible mechanisms. One proposed mechanism involves a shared antigen between the myocardial tissue and the tumor. This mechanism is called molecular mimicry, where the monoclonal antibody attacks both the myocardial tissue and the tumor cell. Management of ICI-induced myocarditis has not been studied by randomized controlled trials or prospective studies, but based on previous case reports and case series it is mostly treated with steroids initially. An ICI rechallenge after temporary discontinuation appears conceivable in many cases, especially given its therapeutic effects, but only limited data are available on the safety of a rechallenge after an irAE. The lack of RCTs regarding rechallenge with an ICI after irAE, more so specifically about myocarditis, along with the overall results and the complexity involved in such cases once again emphasize the need to make decisions on an individual basis by a multidisciplinary expert working group. At the same time, the focus should also be on publishing more data as the need will grow along with the indications for ICI therapies.

Progress in the treatment of soft tissue sarcoma in the 2023 annual meeting of the American Society of Clinical Oncology

Soft tissue sarcoma (STS) is a group of rare malignant tumors originating from mesenchymal tissue, with a high degree of malignancy and a wide range of pathological subtypes. The prognosis varies among different subtypes, and treatment increasingly relies on selecting appropriate treatment methods for different subtypes. Surgical treatment is still the main treatment method at present, and the development of immune and targeted therapy also brings new hope for the treatment of soft tissue sarcoma. Immune checkpoint inhibitors, oncolytic viruses and T cell therapy have shown well safety and efficacy in clinical trials. Targeted drugs such as trabectedin and lenvatinib have changed the treatment pattern of soft tissue sarcoma. Currently, chemotherapy based on doxorubicin and ifosfamide is still the first line treatment for patients with advanced soft tissue sarcoma who have distant metastasis. However, the adverse reactions of doxorubicin limit its application in elderly patients, and trofosfamide has shown good efficacy and safety as an alternative in clinical trials. The efficacy of postoperative radiotherapy has been confirmed, which can reduce the local recurrence rate after surgical resection of soft tissue sarcoma. In summary, multimodal comprehensive treatment has become the main strategy for the treatment of soft tissue sarcoma. The combination of different treatment methods can generate synergistic effects and help patients obtain more clinical benefits, such as the combination of doxorubicin and immune checkpoint inhibitors, and the combination of antiangiogenic drugs and chemotherapy drugs. At the 2023 annual meeting of the American Society of Clinical Oncology (ASCO), oncologists from all over the world reported many researches related to the treatment of soft tissue sarcoma. This article aims to review the new progress in the treatment of soft tissue sarcoma in the 2023 annual meeting of ASCO.

Development of an improved risk stratification scheme for stage II and III colorectal cancers through incorporation of the digital pathology biomarker QuantCRC.

162 Background: There is a need to improve current risk stratification of stage II and III colorectal cancer (CRC) to better inform risk of recurrence and guide adjuvant chemotherapy. The purpose of this study is to examine whether integration of QuantCRC, an AI-based digital pathology biomarker utilizing hematoxylin and eosin-stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines. Methods: ASCO and QuantCRC-integrated risk schemes were applied to an observational cohort of 1,068 stage II and III CRCs. The stage II integrated scheme utilizes pT3 vs. pT4 and QuantCRC-derived risk groups. The stage III integrated scheme utilizes pT1-3 vs. pT4, pN1 vs. pN2, and QuantCRC-derived risk groups. Performance metrics included log-rank test, hazard ratios and Somers’ Dxy rank correlation. Results: Integration of QuantCRC provides improved risk stratification compared to the ASCO scheme for stage II and III CRC. The QuantCRC-integrated scheme placed more stage II tumors in the low-risk group compared to the ASCO scheme (69.3% vs. 60.4%) without decreased 3-year RFS. The QuantCRC-integrated scheme provided larger hazard ratios (HR) for both intermediate-risk (3.04, 95%CI 1.81-5.10, P=2.8x10-5) and high-risk (4.62, 95%CI 2.02-10.61, P=0.0003) groups compared to ASCO intermediate-risk (2.09, 95%CI 1.21-3.63, P=0.008) and high-risk (3.08, 95%CI 1.57-6.01, P=0.001) groups. The QuantCRC-integrated scheme for stage III tumors identified a small group of 80/518 (15.4%) CRCs at very high risk of recurrence with HR of 4.08 (95%CI 2.68-6.23, P=6.5x10-11) compared to a HR of 2.42 (95%CI 1.72-3.38, P=3.1x10-7) for 228/518 (44.0%) high-risk CRCs in the ASCO scheme. QuantCRC-integrated risk groups remained prognostic in stage III CRCs when stratified by presence or absence of any adjuvant chemotherapy. No difference in RFS were seen in QuantCRC-integrated low-risk and intermediate-risk stage III CRCs stratified by 3 vs. 6-months of oxaliplatin-based adjuvant chemotherapy suggesting that these two groups can be treated with 3-months of adjuvant therapy. Conclusions: Incorporation of QuantCRC into risk stratification provides a powerful predictor of RFS that has potential to guide subsequent treatment and surveillance.

New EAU/ASCO guideline recommendations on sentinel node biopsy for penile cancer and remaining challenges from a nuclear medicine perspective.

The European Association of Urology (EAU) and the American Society of Clinical Oncology (ASCO) recently issued updated guidelines on penile cancer, emphasising dynamic sentinel node biopsy (DSNB) as the preferred method for surgical staging among patients with invasive penile tumours and no palpable inguinal lymphadenopathy. This paper outlines the rationale behind this new recommendation and describes remaining challenges, as well as strategies for promoting DSNB worldwide. DSNB offers high diagnostic accuracy with the lowest postoperative complications compared to open or minimally invasive inguinal lymph node dissection (ILND), prompting its preference in the new guidelines. Nevertheless, despite its advantages, there are challenges hampering the widespread adoption of DSNB. This includes the false-negative rate associated with DSNB and the potential negative impact on patient outcome. To address this issue, improvements should be made in several areas, including refining the timing and interpretation of the lymphoscintigraphy and the single photon emission computed tomography/computed tomography images. In addition, the quantity of tracer employed and choice of the injection site for the radiopharmaceutical should be optimised. Finally, limiting the removal of nodes without tracer activity during surgery may help minimise complication rates. Over the years, DSNB has evolved significantly, related to the dedicated efforts and innovations in nuclear medicine and subsequent clinical studies validating its efficacy. It is now strongly recommended for surgical staging among selected penile cancer patients. To optimise DSNB further, multidisciplinary collaborative research is required to improve SN identification for better diagnostic accuracy and fewer complications.

NALIRIFOX, FOLFIRINOX, and Gemcitabine With Nab-Paclitaxel as First-Line Chemotherapy for Metastatic Pancreatic Cancer

The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and nab-paclitaxel (GEM-NABP) as first-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). Analyses comparing NALIRIFOX and GEM-NABP with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) have not yet been reported. To derive survival, response, and toxic effects data from phase 3 clinical trials and compare NALIRIFOX, FOLFIRINOX, and GEM-NABP. After a systematic search of PubMed, Scopus, Embase, and American Society of Clinical Oncology and European Society for Medical Oncology meetings' libraries, Kaplan-Meier curves were extracted from phase 3 clinical trials conducted from January 1, 2011, until September 12, 2023. Phase 3 clinical trials that tested NALIRIFOX, FOLFIRINOX, or GEM-NABP as first-line treatment of metastatic PDAC and reported overall survival (OS) and progression-free survival (PFS) curves were selected. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses of Individual Participant Data reporting guidelines. Individual patient OS and PFS data were extracted from Kaplan-Meier plots of original trials via a graphic reconstructive algorithm. Overall response rates (ORRs) and grade 3 or higher toxic effects rates were also collected. A pooled analysis was conducted, and results were validated via a network meta-analysis. The primary end point was OS. Secondary outcomes included PFS, ORR, and toxic effects rates. A total of 7 trials with data on 2581 patients were analyzed, including 383 patients treated with NALIRIFOX, 433 patients treated with FOLFIRINOX, and 1756 patients treated with GEM-NABP. Median PFS was longer in patients treated with NALIRIFOX (7.4 [95% CI, 6.1-7.7] months) or FOLFIRINOX (7.3 [95% CI, 6.5-7.9] months; [HR], 1.21 [95% CI, 0.86-1.70]; P = .28) compared with patients treated with GEM-NABP (5.7 [95% CI, 5.6-6.1] months; HR vs NALIRIFOX, 1.45 [95% CI, 1.22-1.73]; P < .001). Similarly, GEM-NABP was associated with poorer OS (10.4 [95% CI, 9.8-10.8]; months) compared with NALIRIFOX (HR, 1.18 [95% CI, 1.00-1.39]; P = .05], while no difference was observed between FOLFIRINOX (11.7 [95% CI, 10.4-13.0] months) and NALIRIFOX (11.1 [95% CI, 10.1-12.3] months; HR, 1.06 [95% CI, 0.81-1.39]; P = .65). There were no statistically significant differences in ORR among NALIRIFOX (41.8%), FOLFIRINOX (31.6%), and GEM-NABP (35.0%). NALIRIFOX was associated with lower incidence of grade 3 or higher hematological toxic effects (eg, platelet count decreased 1.6% vs 11.8% with FOLFIRINOX and 10.8% with GEM-NABP), but higher rates of severe diarrhea compared with GEM-NABP (20.3% vs 15.7%). In this systematic review and meta-analysis, NALIRIFOX and FOLFIRINOX were associated with similar PFS and OS as first-line treatment of advanced PDAC, although NALIRIFOX was associated with a different toxicity profile. Careful patient selection, financial toxic effects consideration, and direct comparison between FOLFIRINOX and NALIRIFOX are warranted.

Adverse events of neoadjuvant combination immunotherapy for resectable cancer patients: a systematic review and meta-analysis.

Neoadjuvant combination immunotherapy is changing the treatment landscape for patients with cancer. Exploring the incidence of immune-related adverse events (irAEs) in relation to this novel approach may provide valuable insights for future clinical investigations. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, Cochrane Library, American Society of Clinical Oncology (ASCO), and European Society of Medical Oncology (ESMO) websites were searched for all relevant literature from their inception to November 24, 2023. We then extracted the required data from the included studies and used the R software to analyze the pooled incidence of irAEs. Subgroup analyses examined the pooled incidence of irAEs according to cancer and combination types using a random-effects model. Sixteen studies involving 501 patients were included in the meta-analysis. Considering the heterogeneity of the study design, we analyzed the randomized controlled studies (RCTs) and the single-arm studies separately. In RCTs, the incidence of any-grade irAEs was 95.0% (95% confidence interval [CI] 87.3-99.3) and that of grade ≥3 irAEs was 24.0% (95% CI 13.7-36.0). In single-arm studies, the incidence of any-grade irAEs was 89.4% (95% CI 75.0-98.0) and grade ≥3 irAEs was 20.3% (95% CI 8.7-35.2). In both RCTs and single arms, the most common any- grade irAEs were rash and fatigue, while the most common grade ≥3 irAEs was abnormal liver function and colitis. Due to irAEs, 9.4% of patients in RCTs and 6.9% of patients in single-arm studies did not complete the prescribed neoadjuvant treatment cycle. This study comprehensively summarized the incidence of irAEs in neoadjuvant combination immunotherapy. The occurrence of irAEs varies depending on the cancer and combination types. Our meta-analysis provides clinicians with essential guidance for the management of patients with cancer. https://www.crd.york.ac.uk/prospero, identifier CRD42023387969.

Management of Paraneoplastic Syndromes in the Era of Immune Checkpoint Inhibitors.

Our understanding of paraneoplastic neurologic syndromes (PNS) has blossomed over the past few decades. Clinicians have access to more robust diagnostic criteria and have a heightened index of suspicion for these disorders. Nonetheless, treatment, which typically includes immunosuppression, and response to treatment, varies. Due to persistent difficulty in making a definitive diagnosis, we favor empiric treatment when a possible diagnosis of PNS is suspected, and other alternative causes have substantially been excluded (e.g., infections, toxic-metabolic derangements, metastasis, or leptomeningeal disease). Treatment of the underlying cancer, if identified, is the first therapeutic step and can prevent disease worsening and in rare cases, can reverse neurologic symptoms. In addition to anti-cancer treatment, first line immunotherapies, which include corticosteroids, intravenous immunoglobulins (IVIG), or plasma exchange (PLEX) are typically used. If partial or no benefit is seen, second line immunotherapeutic agents such as rituximab are considered. Additionally, the severity of the initial presentation and possible risk for relapse influences the use of the latter agents. Symptomatic management is also an important component in our practice and will depend on the syndrome being treated. One of the more novel entities we are facing currently is the management of immune checkpoint (ICI)-induced PNS. In those cases, current American Society of Clinical Oncology (ASCO) guidelines are followed.

A Paradigm Shift in Non-Small-Cell Lung Cancer (NSCLC) Diagnostics: From Single Gene Tests to Comprehensive Genomic Profiling.

Lung cancer imposes a burden on the health care system worldwide affecting 2 million people and causing 1.8 million deaths in 2021.More than 85% of all lung cancer cases are reported under Non-small-cell lung cancer (NSCLC). It is critical to discover gene alterations to treat non-small cell lung cancer successfully. The CAP/IASLC/AMP recommendations supported use of polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH) EGFR (epidermal growth factor receptor) mutations and ALK (Anaplastic lymphoma kinase) rearrangements, respectively. A study presented in the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago emphasized the need for comprehensive genomic profiling (CGP) before single gene tests (SGTs) since it demonstrated that SGT can result in the depletion of precious biopsy samples. As a result, the efficacy of thorough genetic Profiling (CGP) is reduced, preventing patients from receiving valuable genetic information about their tumors.

Androgen Receptor Influenced Recurrence Score Correlation in Hormone Positive and HER2 Negative Breast Cancer Indian Patients: A Comparative Approach

Breast cancer (BC) recurrence is a major concern for both patients and healthcare providers. Accurately predicting the risk of BC recurrence can help guide treatment decisions and improve patient outcomes for a disease-free survival. There are several approaches and models that have been developed to predict BC recurrence risk. These include derived clinical assays such as genetic profiling (Oncotye Dx, MammaPrint, CanAssist and others), and algorithm derived open access tools such as Magee equations (ME), CTS5 Calculator and Predict Breast cancer. All the clinical assays are well accepted, but affordability and feasibility remain the challenge due to a noteworthy price tag of USD 3000. As per The American Society of Clinical Oncology (ASCO) updates, open access tools are possible substitutes but the availability of limited information on their applicability is a concern. These tools take into consideration the histopathologic parameters and immunohistochemistry (IHC) biomarkers data for estrogen receptor/progesterone (ER/PR), human epidermal growth factor receptor 2 (HER2), and Ki67. The current study focuses on the application of these tools in a subset of 55 Indian BC patients considering the influence of the androgen receptor (AR) IHC expression profile. AR is a potent target and a close interacting neighbor protein to ER and available literature also suggests their crosstalk expression in BC clinical models. Our comparative recurrence scores (RSs) predictive data showed a statistically significant AR expression correlation with average ME scores. No significance was noted across different prediction tools. The findings are suggestive that ME predictive scores are more relevant and informative compared to other online tools and with an additional AR IHC expression analysis the recurrence prediction might prove to be beneficial and feasible to many deprived BC patients.

Navigating through novelties concerning mCRC treatment-the role of immunotherapy, chemotherapy, and targeted therapy in mCRC.

Over the course of nearly six decades since the inception of initial trials involving 5-FU in the treatment of mCRC (metastatic colorectal cancer), our progressive comprehension of the pathophysiology, genetics, and surgical techniques related to mCRC has paved the way for the introduction of novel therapeutic modalities. These advancements not only have augmented the overall survival but have also positively impacted the quality of life (QoL) for affected individuals. Despite the remarkable progress made in the last two decades in the development of chemotherapy, immunotherapy, and target therapies, mCRC remains an incurable disease, with a 5-year survival rate of 14%. In this comprehensive review, our primary goal is to present an overview of mCRC treatment methods following the latest guidelines provided by the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), and the American Society of Colon and Rectal Surgeons (ASCRS). Emphasis has been placed on outlining treatment approaches encompassing chemotherapy, immunotherapy, targeted therapy, and surgery's role in managing mCRC. Furthermore, our review delves into prospective avenues for developing new therapies, offering a glimpse into the future of alternative pathways that hold potential for advancing the field.

Healthcare professionals' knowledge of and compliance with the ASCO/ESMO/GLIM guidelines for the diagnosis and management of cancer cachexia (CC): the ASSIST-CC baseline findings in Uganda.

More than 50% of people with advanced cancer suffer from cancer-related cachexia (CC) - a major contributor to morbidity and mortality. Despite the lack of local guidelines on CC diagnosis and management in Uganda, the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO) and the Global Leadership Initiative on Malnutrition (GLIM) developed guidelines on CC screening and management. However, the level of knowledge on CC and compliance with the available guidelines among Ugandan oncology health professionals is unknown. This study aimed to assess the level of awareness and knowledge of CC diagnosis and management and compliance with the ASCO/ESMO/GLIM guidelines on CC among healthcare professionals (HCPs) involved in the care of cancer patients. In this phase one, a self-administered structured questionnaire developed using the ASCO/ESMO and GLIM guidelines on diagnosis and management of CC was used to assess the level of awareness, and knowledge of 200 health professionals from three hospital settings on CC, and compliance with the ASCO/ESMO/GLIM guidelines on CC related core communication, barriers to communication, clinician training in communication, discussing goals of care, treatment options and meeting the needs of the underserved populations. The data were entered into Research Electronic Data Capture software analysed using STATA version 18.0 software. The overall objectively correct knowledge score of CC diagnosis criteria was 67.5% (n = 135), yet there was a much lower level of awareness about ASCO/ESMO/GLIM guidelines on CC at 30% (n = 60) and only 21% (n = 42) of the HCPs have ever assessed Quality of life of CC patients. The compliance with ASCO/ESMO/GLIM guidelines on nutritional interventions for patients with CC varied across the variables markedly, ranging from 25.1% (n = 50) to 81% (n = 162) for the specific ASCO/ESMO/GLIM guidelines' recommendations. Whereas compliance with the guidelines on discussing goals of care, prognosis, treatment options and end-of-life care scored the highest in most variables, most HCPs exhibited low compliance with the discussion about patients' end-of-life preferences early in the course of incurable illness (49.8%, n = 99). There were statistically significant differences between the mean scores of only two variables among the three hospitals in compliance with ASCO/ESMO/GLIM guidelines on the provision. This study indicated that the overall objectively correct knowledge of CC diagnosis criteria was inadequate, with a much lower level of awareness about the ASCO/ESMO/GLIM guidelines on CC and a handful of the HCPs have ever assessed the quality of life of CC patients. Quality improvement interventions on CC diagnosis and management should prioritize improving the level of knowledge on CC, diagnostic criteria and patient-clinician communication, including discussion about patients' end-of-life care using standardised tools such as ASCO/ESMO or GLIM guidelines on CC using a multidisciplinary team approach.

Pharmacological methods for ovarian function and fertility preservation in women with cancer: A literature review.

Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality. The effect of chemotherapy can range from minimal effects to complete ovarian atrophy. Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility. Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy decreases the gonadotoxic effect of chemotherapy, thereby diminishing the chance of developing premature ovarian insufficiency (POI). At present, the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function. Notably, most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer, with a considerably small number of studies on patients with hematological malignancies. Furthermore, most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk, regardless of the hormone receptor status. In addition, studies on hematological malignancies have yielded negative results; nevertheless, the findings must be interpreted with caution owing to numerous limitations. Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm, oocyte, and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible. In this manuscript, we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data, as well as future perspectives in this field that upcoming research should focus on.

Emerging Antibody-Drug Conjugate Therapies and Targets for Metastatic Renal Cell Carcinoma

Background: Approximately 30% of renal cell carcinoma (RCC) cases present with de novo metastatic disease, while 20% to 30% of those with localized disease will develop metastases following surgical resection. Various drug classes have been investigated to treat RCC, including cytokine-based therapies, small molecule Vascular Endothelial Growth Factor (VEGF) tyrosine kinase inhibitors (TKIs) and antibody-based therapies. Up to 58% of patients fail to respond to primary immune checkpoint inhibitor (ICI) therapy, and nearly all initial responders experience disease progression due to the development of secondary resistance. Consequently, novel treatment options are being investigated. Objective: Review the rapidly evolving ADC therapeutic landscape in metastatic RCC including recent trials, emerging ADCs targets, and future directions for ADCs in the treatment of advanced RCC. Methods: Literature review using the MEDLINE database on important trials and presentations from the American Society of Clinical Oncology (ASCO), and the European Society for Medical Oncology (ESMO) conferences. Key words used included “renal cell carcinoma,” “RCC,” “metastatic RCC,” “advanced RCC,” “antibody-based therapies,” “immunotherapy,” “clinical trials,” and “emerging drugs.” Specifically for review of ADCs in RCC, the following search string was used with additional review of bibliographies from retrieved papers: “((antibody drug conjugate) OR (antibody-dependent cellular cytotoxicity) OR (chimeric antigen receptor)) AND ((kidney cancer) OR (renal cell carcinoma))”. Results: Several promising targets including MMP14, EGFR, MCT4, CA9, MET, CDH13, B7-H3, and PSMA were identified with relevant preclinical and clinical studies reviewed. Conclusions: While ADCs therapeutics have not shown benefit to date for renal cell carcinoma, there are ample promising candidates and targets for future research.

Emetic risk classification and evaluation of the emetogenicity of antineoplastic agents—updated MASCC/ESMO consensus recommendation

PurposeOur goal was to identify new anticancer agents approved by the US Food and Drug Administration (FDA) and the European Medical Agency (EMA) since the 2016 MASCC/ESMO antiemetic update and classify their emetic potential.MethodsThe MASCC/ESMO Expert Panel classified the emetogenicity of the identified new antineoplastic agents based on nonsystematic reviews of randomized controlled trials, analysis of product labeling, and evaluation of emetic classification in other international guidelines and informal consensus. The emetogenic classification system for oral anticancer agents was revised into two emetic risk categories (minimal–low; moderate–high) to be consistent with the system reported by ASCO (American Society of Clinical Oncology) in their 2017 guideline update. The previously employed four emetic risk classification categories for intravenously administered antineoplastic agents were retained for this update.ResultsFrom June 2015 to January 2023, 107 new antineoplastic agents (44 intravenously administered and 63 orally administered agents) were identified. The reported incidence of vomiting varied significantly across studies for many agents, especially for oral anticancer agents.ConclusionThe MASCC/ESMO Expert Panel acknowledges the limitations of our efforts to classify the emetic potential of anticancer agents, especially the imprecision associated with oral agents. However, we have attempted to provide a reasonable approximation of the emetic risk associated with new antineoplastic agents by searching the available literature and reviewing other available international antiemetic guidelines.

Immunotherapy for hepatocellular carcinoma: molecular pathogenesis and clinical research progress

Abstract The treatment of hepatocellular carcinoma (HCC) is advancing rapidly in the 21st century. Although there are various treatment methods, the most promising breakthrough seems to be in immunotherapy. Recent guidelines from the American Society of Clinical Oncology and the European Association for the Study of the Liver have recommended immunotherapies with strong antitumor effects for HCC treatment. Emerging systemic therapeutic strategies, such as immune checkpoint inhibitors combined with targeted therapy or local treatment, are among the most promising for improving overall and tumor-free survival times in patients with HCC. This review analyzes the molecular mechanisms of existing immune checkpoint inhibitors, vaccines, and chimeric antigen receptor–T cells; summarizes the latest progress in relevant clinical research; and outlines future trends and opportunities for HCC immunotherapy.

HER2/ERBB2 copy number analysis by targeted next-generation sequencing in breast cancer.

A combination of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) is the current standard of care for HER2 evaluation in breast cancer. Here, we investigate the potential clinical utility of next-generation sequencing (NGS)-derived HER2/ERBB2 copy number (CN) data for predicting HER2 status as defined by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. In total, 294 locally recurrent and metastatic breast cancers previously tested by targeted hybrid capture-based NGS and by HER2 IHC/FISH were included. Analyses focused on the ERBB2 median log2 ratios and start-end genomic coordinates from NGS, average HER2 CN and HER2/CEP17 ratios from FISH, and the HER2 IHC scores. We also determined a more stringent log2 ratio cutoff to predict HER2-positive status with 100% specificity. Sixty-four (22%) cases were HER2 positive and 230 (78%) were HER2 negative by ASCO/CAP guidelines. The ERBB2 median log2 ratios from NGS strongly correlated with HER2 status by IHC/FISH (area under receiver operator characteristic curve = 0.951). ERBB2 log2 ratio more than 1.7 was 100% specific for HER2-positive results by IHC/FISH. Start and end genomic coordinates for regions of gain near ERBB2 by NGS also predicted HER2 status. Copy number data from our NGS panel strongly correlate with HER2 status. Using a stringent cutoff, ERBB2 log2 ratio accurately predicts HER2 positivity with high specificity. The NGS CN assessment may have utility in determining HER2 status in certain clinical settings.

Transcatheter prosthetics in post-radiation aortic stenosis: a review of literature

Aortic stenosis belongs to the most common acquired cardiac defects in adults, affecting about 2 % of those over 65 years old and 4 % of those over 85 years old. One of the common causes of aortic stenosis is radiation therapy of the mediastinum for malignant neoplasms localised in the thorax. According to the American Society of Clinical Oncology, 10–30 % of patients receiving radiation therapy tend to develop cardiovascular complications, usually after an average follow-up period of 5 to 10 years. About 80 % of cardiovascular complications of radiation therapy are valve diseases, aortic stenosis accounting for a significant part of them. Radiation causes late cicatrisation, fibrous thickening, retraction and calcification of aortic valve cusps, contributing to the restriction of their movement and therefore to the narrowing of the aortic valve orifice. Patients with aortic valve stenosis have an average lifespan of about 3 years after coronary symptoms or syncopal conditions appear, and about 1.5 years after congestive heart failure begins to manifest. Aortic valve prosthetics is the sole effective and radical treatment method for patients with aortic valve stenosis that allows to improve their condition and prolong their life. Transcatheter aortic valve prosthetics are the treatment of choice in this category of patients.

ASCO 2023: highlights in breast cancer

SummaryThe 2023 annual meeting of the American Society of Clinical Oncology (ASCO) was again held in June 2023 in Chicago. While not immediately practice changing, results from several interesting studies in the field of breast cancer (BC) were reported. In the phase III NATALEE trial, the addition of 3 years of ribociclib to standard adjuvant endocrine therapy resulted in a significant improvement in invasive disease-free survival (iDFS), making this the second positive study of CDK4/6 inhibitors in the adjuvant setting. A subgroup analysis from the MONARCHe trial indicated sustained benefit of adjuvant abemaciclib in the subset of patients with low dose intensity. Long-term outcome of the neoadjuvant phase II PHERgain trial indicated excellent iDFS results in patients receiving neoadjuvant trastuzumab and pertuzumab without chemotherapy based upon PET metabolic response as a dynamic biomarker. In a biomarker analysis from the SOFT trial, more high-risk tumors were observed in the very young patient subset, while the PAM50 risk-of-recurrence score was not predictive for benefit of ovarian function suppression. A large retrospective analysis evaluated the role of adjuvant chemotherapy in small, node-negative triple-negative breast cancer. A clear benefit for chemotherapy was only seen in tumors &gt; 10 mm of size. In metastatic HR-positive breast cancer, the PALMIRA trial with palbociclib beyond progression yielded negative results. An update from the PADA-1 trial again indicates the promising role of repeated liquid biopsies for treatment guidance in metastatic disease. Patritumab deruxtecan, a HER3-directed antibody–drug conjugate yielded promising response rates in HER2-negative metastatic breast cancer patients. In addition, several retrospective analyses focused on the important question of treatment sequencing.