Nivolumab plus Ipilimumab in Non-Small-Cell Lung Cancer

To the Editor: Although more than 10% of the patients in the CheckMate 227 trial conducted by Hellmann et al. (Nov. 21 issue)(1) had never smoked, the effect of smoking status on survival was not fully discussed. Striking differences in the clinical and molecular characteristics of lung cancers between smokers and those who have never smoked have been identified, suggesting that the cancers are separate entities.(2) In one trial,(3) patients who had never smoked had poorer responses to nivolumab (as compared with docetaxel) than current or former smokers (hazard ratio for overall survival, 1.02 vs. 0.70). In a meta-analysis involving . .

Stage 3 N2 lung cancer: A multidisciplinary therapeutic conundrum

The treatment of stage III N2 non-small cell lung cancer (NSCLC) remains debated. There is an absence of a universally agreed definition of resectability for this heterogeneous group and a lack of trial data. We reviewed and compared current international guidelines and evidence surrounding management of stage III N2 NSCLC. The Irish and Australian guidelines advise subcategorising N2 disease into N2a (may be resectable) and N2b (never resectable). On the contrary, American and British guidelines avoid subcategorising N2 disease, emphasising importance of local MDT decisions. It is suggested that evidence for resection of stage III tumours is relatively weak, but that stage IIIA should generally be considered for resection, and stage IIIB is not recommended for resection. For resectable disease, surgery may be combined with neoadjuvant chemoimmunotherapy, or adjuvant chemotherapy followed by immunotherapy and radiotherapy in selected patients. There is some evidence that technically resectable disease can be treated solely with radiotherapy with similar outcomes to resection. In the event of unresectable disease, chemoradiotherapy has been the traditional management option. However, recent studies with chemoradiotherapy alongside immunotherapy appear promising. There are many factors that influence the treatment pathway offered to patients with stage III N2 NSCLC, including patient factors, team expertise, and local resources. Therefore, the role of MDTs in defining resectability and formulating an individualised treatment plan is crucial. [Abstract copyright: © 2024. Crown.

Cancer Predisposition Genes in Adolescents and Young Adults (AYAs): a Review Paper from the Italian AYA Working Group

Purpose of Review: The present narrative systematic review summarizes current knowledge on germline gene mutations predisposing to solid tumors in adolescents and young adults (AYAs). Recent Findings: AYAs with cancer represent a particular group of patients with specific challenging characteristics and yet unmet needs. A significant percentage of AYA patients carry pathogenic or likely pathogenic variants (PV/LPVs) in cancer predisposition genes. Nevertheless, knowledge on spectrum, frequency, and clinical implications of germline variants in AYAs with solid tumors is limited. Summary: The identification of PV/LPV in AYA is especially critical given the need for appropriate communicative strategies, risk of second primary cancers, need for personalized long-term surveillance, potential reproductive implications, and cascade testing of at-risk family members. Moreover, these gene alterations may potentially provide novel biomarkers and therapeutic targets that are lacking in AYA patients. Among young adults with early-onset phenotypes of malignancies typically presenting at later ages, the increased prevalence of germline PV/LPVs supports a role for genetic counseling and testing irrespective of tumor type

Parenting practices and adolescent eating behaviors in African American families.

Parents play an important role in developing the eating behaviors of their children by adopting specific parenting practices. As the prevalence of obesity is high amongst African American adolescents, investigations into associations of specific parenting practices and adolescents' eating behaviors are essential. In this exploratory study, 14 African American parent-adolescent dyads were interviewed to characterize the influence of eight different parenting practices on the consumption of three main food categories (dairy, fruits and vegetables, and unhealthy snacks). The results revealed that authoritarian parenting practices were correlated with a higher BMI percentile in adolescents, whereas modeling and monitoring are correlated with a higher parent BMI. In addition, reasoning, monitoring, modeling, and authoritative parenting practices were associated with less unhealthy snack consumption among adolescents. Reasoning and monitoring were the only parenting practices associated with higher fruit and vegetable consumption. Finally, a significant correlation was found between eating fruits and vegetables and unhealthy snacks and the location of eating. In conclusion, different parenting practices and environmental factors may impact BMI and food consumption of African American dyads. The results of this study can be used to guide improvement in, and/or development of, nutritional education interventions considering the cultural differences of racial minorities

Circulating tumor cell gene expression and plasma AR gene copy number as biomarkers for castration-resistant prostate cancer patients treated with cabazitaxel

Background: Cabazitaxel improves overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients progressing after docetaxel. In this prospective study, we evaluated the prognostic role of CTC gene expression on cabazitaxel-treated patients and its association with plasma androgen receptor (AR) copy number (CN). Methods: Patients receiving cabazitaxel 20 or 25 mg/sqm for mCRPC were enrolled. Digital PCR was performed to assess plasma AR CN status. CTC enrichment was assessed using the AdnaTest EMT-2/StemCell kit. CTC expression analyses were performed for 17 genes. Data are expressed as hazard ratio (HR) or odds ratio (OR) and 95% CI. Results: Seventy-four patients were fully evaluable. CTC expression of AR-V7 (HR=2.52, 1.24–5.12, p=0.011), AKR1C3 (HR=2.01, 1.06–3.81, p=0.031), AR (HR=2.70, 1.46–5.01, p=0.002), EPCAM (HR=3.75, 2.10–6.71, p< 0.0001), PSMA (HR=2.09, 1.19–3.66, p=0.01), MDK (HR=3.35, 1.83–6.13, p< 0.0001), and HPRT1 (HR=2.46, 1.44–4.18, p=0.0009) was significantly associated with OS. ALDH1 (OR=5.50, 0.97–31.22, p=0.05), AR (OR=8.71, 2.32–32.25, p=0.001), EPCAM (OR=7.26, 1.47–35.73, p=0.015), PSMA (OR=3.86, 1.10–13.50, p=0.035), MDK (OR=6.84, 1.87–24.98, p=0.004), and HPRT1 (OR=7.41, 1.82–30.19, p=0.005) expression was associated with early PD. AR CN status was significantly correlated with AR-V7 (p=0.05), EPCAM (p=0.02), and MDK (p=0.002) expression. In multivariable model, EPCAM and HPRT1 CTC expression, plasma AR CN gain, ECOG PS=2, and liver metastases and PSA were independently associated with poorer OS. In patients treated with cabazitaxel 20 mg/sqm, median OS was shorter in AR-V7 positive than negative patients (6.6 versus 14 months, HR=3.46, 1.47–8.17], p=0.004). Conclusions: Baseline CTC biomarkers may be prognosticators for cabazitaxel-treated mCRPC patients. Cabazitaxel at lower (20 mg/sqm) dose was associated with poorer outcomes in AR-V7 positive patients compared to AR-V7 negative patients in a post hoc subgroup analysis. Trial registration: Clinicaltrials.govNCT03381326. Retrospectively registered on 18 December 2017

Relationship between family racial/ethnic backgrounds, parenting practices and styles, and adolescent eating behaviors.

Obesity is more prevalent among racial minority children in the United States, as compared to White children. Parenting practices can impact the development of children's eating behaviors and habits. In this study, we investigated the relationships among racial/ethnic backgrounds, parenting practices and styles, and eating behaviors in adolescents. Fifty-one parent-adolescent dyads were interviewed to characterize parenting practices and styles, as well as the consumption of dairy, fruits and vegetables, and unhealthy snacks. Height and weight were measured to calculate parent BMI and adolescent BMI-for-age percentiles. Three parenting practice categories-modeling, authoritative, and authoritarian-were found to be related to race/ethnicity. A higher score in authoritarian parenting practices was related to higher BMI percentiles among African American adolescents, whereas a higher score in monitoring practices was related to lower BMI percentiles among non-Hispanic White adolescents. Modeling, reasoning, and monitoring led to higher consumption of fruits and vegetables among adolescents; however, the consumption of unhealthy snacks was higher with rule-setting and lower with reasoning and authoritative practices. Finally, an analysis of the relationships between environmental factors and snack intake showed that adolescents consumed significantly more unhealthy snacks when performing other activities while eating. In conclusion, the findings from this study suggest that families' racial heritages are related to their parenting practices, BMI percentiles, and their adolescents' food consumption and eating behaviors. The results of this study can be used to develop and improve adolescent nutrition education and interventions with consideration of their racial/ethnic backgrounds

Application of the Meet-URO score to metastatic renal cell carcinoma patients treated with second- and third-line cabozantinib

Background: The addition of neutrophil-to-lymphocyte ratio (NLR) and bone metastases to the International Metastatic RCC Database Consortium (IMDC) score (by the Meet-URO score) has been shown to better stratify pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. This study aimed to validate the Meet-URO score in patients receiving cabozantinib to assess its predictivity and prognostic role. Methods: A multicenter retrospective analysis evaluated mRCC patients receiving ⩾second-line cabozantinib. NLR, IMDC score and bone metastases were assessed before the start of cabozantinib. The primary endpoint was overall survival (OS). Harrell’s c-index was calculated to compare the accuracy of the prediction of the two scores. Results: Overall, 174 mRCC patients received cabozantinib as second and third line (51.7% and 48.3%, respectively) with a median follow-up of 6.8 months. A shorter median overall survival (mOS) was observed for the IMDC poor-risk group, NLR ⩾3.2 and the presence of bone metastases, while the IMDC intermediate-risk group had a similar mOS to the favourable-risk one. Applying the Meet-URO score, three risk groups were identified: group 1 (55.2% of patients) with a score of 0–3, group 2 (38.5%) with a score of 4–8 and group 3 (6.3%) with a score of 9. Compared to group 1 (mOS: 39.4 months), a statistically significant worse mOS was observed in group 2 (11.2 months) and group 3 (3.2 months) patients, respectively. The Meet-URO c-index score was 0.640, showing a higher discriminative ability than the IMDC score (c-index: 0.568). Conclusion: This analysis showed that the Meet-URO score provides a more accurate prognostic stratification than the IMDC score in mRCC patients treated with ⩾second-line cabozantinib besides nivolumab. Moreover, it is an easy-to-use tool with no additional costs for clinical practice (web-calculator is available at: https://proviso.shinyapps.io/Meet-URO15_score/). Future investigations will include the application of the Meet-URO score to the first-line immunotherapy-based combination therapies

Immune Checkpoint Inhibitors in Advanced Prostate Cancer: Current Data and Future Perspectives

In the last 10 years, many new therapeutic options have been approved in advanced prostate cancer (PCa) patients, granting a more prolonged survival in patients with metastatic disease, which, nevertheless, remains incurable. The emphasis on immune checkpoint inhibitors (ICIs) has led to many trials in this setting, with disappointing results until now. Therefore, we discuss the immunobiology of PCa, presenting ongoing trials and the available clinical data, to understand if immunotherapy could represent a valid option in this disease, and which subset of patients may be more likely to benefit. Current evidence suggests that the tumor microenvironment needs a qualitative rather than quantitative evaluation, along with the genomic determinants of prostate tumor cells. The prognostic or predictive value of immunotherapy biomarkers, such as PD-L1, TMB, or dMMR/MSI-high, needs further evaluation in PCa. Monotherapy with immune checkpoint inhibitors (ICIs) has been modestly effective. In contrast, combined strategies with other standard treatments (hormonal agents, chemotherapy, PARP inhibitors, radium-223, and TKIs) have shown some results. Immunotherapy should be better investigated in biomarker-selected patients, particularly with specific pathway aberrations (e.g., AR-V7 variant, HRD, CDK12 inactivated tumors, MSI-high tumors). Lastly, we present new possible targets in PCa that could potentially modulate the tumor microenvironment and improve antitumor activity with ICIs