Lung Carcinoids in Adolescents and Young Adults (AYAs): A Still Overlooked Clinical Entity.

Pulmonary carcinoids (PCs) are rare neoplasms involving typical and atypical carcinoids (TCs and ACs), defined histologically by absent or focal necrosis and mitotic counts (<2/mm vs. 2-10/mm), respectively. Although uncommon overall, TCs and ACs represent the most frequent non-hematologic malignancies in the pediatric population.

Heterogeneity of progression-free-survival surrogacy by sex in randomized trials testing immunotherapy in NSCLC.

Background: The surrogacy of progression-free survival (PFS) for overall survival (OS) at the trial-level in randomized clinical trials (RCTs) testing immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancers (NSCLC) is influenced by several clinical-pathological factors. However, potential heterogeneity of PFS surrogacy according to patients' sex has never been investigated.

Methods: RCTs testing ICIs as monotherapy or combined with chemotherapy in patients with advanced NSCLC reporting hazard ratios (HR) for PFS and OS according to patients' sex were included.

Aprepitant use during chemotherapy and association with survival in women with early breast cancer.

Background: Preclinical studies have shown that aprepitant, an antiemetic used to prevent chemotherapy-induced nausea and vomiting, slows mammary tumor growth and progression. Here, we evaluated the association between aprepitant and survival in a large cohort of women with early breast cancer.

Methods: Using linked nationwide registry data, we identified 13,811 women diagnosed with early breast cancer between 2008 and 2020 in Norway, who received chemotherapy and antiemetics.

Point of view: Genomic landscape and molecularly informed therapy in thymic carcinoma and other advanced thymic epithelial tumors.

In this issue of Med, Möhrmann et al. present a comprehensive analysis of 81 advanced thymic epithelial tumors (TETs). The study offers insights into the tumor mutational landscape, germline alterations, and the identification of different immunological subsets.

Sex-Related Differences in Immunotherapy Toxicities: Insights into Dimorphic Responses.

Significant sex-based differences exist in the immune system and antitumor immune responses, potentially leading to variations in both the efficacy and toxicity of anticancer immunotherapies. Women generally mount stronger innate and adaptive immune responses than men, which can result in more severe immune-related adverse events (irAEs) during treatments with immune checkpoint inhibitors (ICIs). However, the importance of sex dimorphism in the safety of cancer immunotherapy remains underexplored in clinical oncology, despite its profound implications for treatment outcomes.

Sex hormones, the anticancer immune response, and therapeutic opportunities.

Sex-based differences have been observed in the incidence and prognosis of various cancers, as well as in the response to immune check point inhibitors (ICIs). These disparities are partially attributed to sex-based differences in the molecular characteristics of the anticancer immune response, which are largely influenced by sex hormones. Here, we provide a comprehensive overview on how sex hormones affect innate and adaptive immunity and contribute to shaping the features of tumor immune microenvironment and response to anticancer immunotherapy.

Surrogate endpoints for overall survival in randomized clinical trials testing antibody-drug conjugates.

Background: The surrogacy of overall response rate (ORR) or progression-free survival (PFS) for overall survival (OS) at the trial-level in randomized clinical trials (RCTs) testing antibody-drugs conjugates (ADC) has never been investigated.

Methods: RCTs testing ADCs in patients with advanced solid tumors and reporting data on OS and PFS and/or ORR were analyzed. The main objective was to assess the trial-level association between the surrogate endpoints (ORR or PFS) and the reference endpoint (OS), overall and in subgroups of trials defined by tumor type, number of previous lines of systemic treatments, and specific ADC features.

First Report of Pembrolizumab Activity in KIT-Mutated Thymic Carcinoma.

The antitumor activity of immunotherapy is strongly influenced by the presence of driver gene mutations/translocations. For this reason, knowledge of the predictive value of specific genetic alterations in relation to anti-PD(L)1 activity is highly useful for the clinical decision making process in many solid tumors, particularly in Non-Small Cell Lung Cancer. Although data on the correlation between genetic alterations and response to immunotherapy are available in the majority of common cancers, data are lacking in the subset of patients with KIT-mutated Thymic Carcinoma (TC).

The pathologic and genomic evolution of primary malignant phyllodes tumors of the breast: retrospective cohort study and case-control genomic analysis.

Background: In patients with phyllodes tumors of the breast, the presence of mediator of RNA polymerase II transcription subunit 12 homolog mutations (MED12m) and a history of previous fibroadenoma may predict better outcomes. To aid in the prognostication of malignant phyllodes tumors of the breast (B-MPT), we assessed the prognostic value of fibroadenoma-like areas (supposed to have stemmed from a pre-existing fibroadenoma) and MED12m, in patients with resected primary B-MPTs.

Methods: We conducted a single-center, retrospective, cohort study including all consecutive patients aged ≥18 years old, with non-metastatic B-MPT, who underwent surgery from January 2000 to December 2021.

Surrogate End Points for Overall Survival in Neoadjuvant Randomized Clinical Trials for Early Breast Cancer.

Purpose: To assess trial-level surrogacy value for overall survival (OS) of the pathologic complete response (pCR) and invasive disease-free survival (iDFS) in randomized clinical trials (RCTs) for early breast cancer (BC).

Methods: Individual patient data of neoadjuvant RCTs with available data on pCR, iDFS, and OS were included in the analysis. We used the coefficient of determination from weighted linear regression models to quantify the association between treatment effects on OS and on the surrogate end points.

The Rare Entity of Basaloid Thymic Carcinoma: A Multicentric Retrospective Analysis from the Italian Collaborative Group for ThYmic MalignanciEs (TYME).

Background: thymic basaloid carcinoma (BTC) is an extremely rare tumor, and very little data are available on BTC's biology, clinical behavior, drug sensitivity, and patient outcomes.

Methods: We performed a retrospective observational study on patients diagnosed with BTC in 11 referral centers of TYME. All BTC diagnoses were reviewed by the referring pathologist.

Gender-based differences in the efficacy of anti-EGFR/BRAF/MEK targeted therapy in patients with BRAF-mutated metastatic colorectal cancer.

Objectives: We previously showed that men with melanoma harboring BRAF mutations had significantly lower benefit from targeted therapy as compared with women Here we explored the hypothesis that such gender-based dimorphism in the efficacy of BRAF-pathway blockade extends to other tumor histotypes carrying pathogenic BRAF-mutations.

Methods: We retrospectively analyzed data from a cohort of patients with advanced colorectal-cancer (CRC) harboring BRAF V600E mutations, treated with anti-EGFR/BRAF/MEK targeted therapy. The primary objective was to assess the association between gender and outcome of patients treated with targeted therapy, in terms of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).

Estrogen Signaling in Early-Stage Breast Cancer: Impact on Neoadjuvant Chemotherapy and Immunotherapy.

Neoadjuvant chemoimmunotherapy (NACIT) has been shown to improve pathologic complete response (pCR) rates and survival outcomes in stage II-III triple-negative breast cancer (TNBC). Promising pCR rate improvements have also been documented for selected patients with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC). However, one size does not fit all and predicting which patients will benefit from NACIT remains challenging.

Outcomes of patients with advanced solid tumors who discontinued immune-checkpoint inhibitors: a systematic review and meta-analysis.

Background: The outcome of patients with metastatic tumors who discontinued immune checkpoint inhibitors (ICIs) not for progressive disease (PD) has been poorly explored. We performed a meta-analysis of all studies reporting the clinical outcome of patients who discontinued ICIs for reasons other than PD.

Methods: We searched PubMed, Embase and Scopus databases, from the inception of each database to December 2023, for clinical trials (randomized or not) and observational studies assessing PD-(L)1 and CTLA-4 inhibitors in patients with metastatic solid tumors who discontinued treatment for reasons other than PD.

Surrogate endpoints for overall survival in randomized clinical trials testing immune checkpoint inhibitors: a systematic review and meta-analysis.

Introduction: There is debate on which are the best surrogate endpoint and metric to capture treatment effect on overall survival (OS) in RCTs testing immune-checkpoint inhibitors (ICIs).

Methods: We systematically searched for RCTs testing ICIs in patients with advanced solid tumors. Inclusion criteria were: RCTs i) assessing PD-(L)1 and CTLA-4 inhibitors either as monotherapy or in combination with another ICI, and/or targeted therapy, and/or chemotherapy, in patients with advanced solid tumors; ii) randomizing at least 100 patients.

"Heterogeneity of treatment effect on patients' long-term outcome according to pathological response type in neoadjuvant RCTs for breast cancer.".

Introduction: To provide evidence explaining the poor association between pCR and patients' long-term outcome at trial-level in neoadjuvant RCTs for breast cancer (BC), we performed a systematic-review and meta-analysis of all RCTs testing neoadjuvant treatments for early-BC and reporting the hazard ratio of DFS (HR) for the intervention versus control arm stratified by pathological response type (i.e., pCR yes versus no).

Immune-checkpoint inhibitors in anal squamous cell carcinoma: a systematic review and meta-analysis.

Introduction: Squamous cell carcinoma of the anus (SCCA) is a rare tumor. While most patients with locally advanced disease are cured with chemo-radiotherapy, about a quarter eventually experience metastatic recurrence. Standard treatment for advanced disease is chemotherapy, but recently evidence on the activity of immunotherapy has been reported.

Primary malignant phyllodes tumors of the breast: A retrospective analysis from a referral center.

Background: The treatment for primary malignant phyllodes tumors of the breast (B-MPT) consists of wide local excision with negative margins (≥1 cm). However, because of their rarity, prognostic factors, type of surgery and adjuvant treatments are still a matter of debate.

Methods: We conducted a single-center retrospective study to describe outcomes and prognostic factors of patients with primary B-MPT, who underwent breast surgery from January 2000 to December 2021.

Guideline-Based Follow-Up Outcomes in Patients With Gastrointestinal Stromal Tumor With Low Risk of Recurrence: A Report From the Italian Sarcoma Group.

Importance: Gastrointestinal stromal tumor (GIST) follow-up is recommended by international guidelines, but data on the role of follow-up in patients with low relapse risk are missing. For these patients, the potential benefit of anticipating recurrence detection should be weighed against psychological burden and radiologic examination loads in terms of costs and radiation exposure.

Objective: To evaluate the outcomes of guideline-based follow-up in low-risk GIST.

Sex dimorphism and cancer immunotherapy: May pregnancy solve the puzzle?

In the immunoncology era, growing evidence has shown a clear sex dimorphism in antitumor immune response with a potential impact on outcomes upon immunecheckpoint blockade (ICI) in patients with cancer. Sex dimorphism could affect tumor microenvironment composition and systemic anticancer immunity; however, the modifications induced by sex are heterogeneous. From a clinical perspective, six metanalyses have explored the role of sex in cancer patients receiving ICI with conflicting results.

Fine-Tuning Adjuvant Endocrine Therapy for Early-Stage Breast Cancer: An Expert Consensus on Open Issues for Future Research.

After decades of research, improving the efficacy of adjuvant endocrine therapy (ET) for early-stage breast cancer becomes increasingly difficult. Beyond technological breakthroughs and the availability of new classes of drugs, further improvement of adjuvant ET will require applying a rigorous research approach in poorly investigated areas. We critically discuss some key principles that should inform future research to improve ET efficacy, including identifying specific subgroups of patients who can benefit from escalating or de-escalating approaches, optimizing available and new treatment strategies for different clinical contexts, and dissecting the direct and indirect biological effects of therapeutic interventions.

The rare entity of gastrointestinal leiomyosarcomas: An Italian multicenter retrospective study in high-volume referral centers.

Background: After a huge efficacy of imatinib in treating patients with gastrointestinal stromal tumors (GISTs) was proven, a maximum effort was made to make a differential diagnosis between GISTs and gastrointestinal leiomyosarcomas (GI-LMS), showing the latter to be an extremely rare tumor entity. Limited data on GI-LMS biology, clinical behavior and drug-sensibility are available, and the clinical decision-making in this subgroup of patients is usually challenging.

Methods: We conducted a multicenter, retrospective observational study on patients with diagnosed GI-LMS from 2004 to 2020 within six high-volume referral centers in Italy.