Nutritional status associates with immunotherapy clinical outcomes in recurrent or metastatic head and neck squamous cell carcinoma patients.

BACKGROUND: Beyond programmed death-ligand 1 (PD-L1) assessed by the combined positive score (CPS) and tumor mutational burden (TMB), no other biomarkers are approved for immunotherapy interventions. Here, we investigated whether additional clinical and pathological variables may impact on immunotherapy outcomes in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients. METHODS: R/M HNSCC patients treated with immunotherapy were reviewed. Analyzed variables at baseline included: clinicopathological, laboratory, and variables reflecting the host nutritional status such as the prognostic nutritional index (PNI) and albumin. The primary endpoint was progression free survival (PFS). The secondary endpoints were overall survival (OS) and objective response rate (ORR). Univariable and multivariable Cox models were fitted and random forest algorithm was used to estimate the importance of each prognostic variable. RESULTS: A total of 100 patients were treated with immunotherapy; 50% with single agent and 50% with experimental immunotherapy combinations. In the multivariable analysis, both ECOG performance status (HR: 1.73; 95%CI 1.07-2.82; p = 0.03) and PNI levels (10-point increments, HR: 0.66; 0.46-0.95; p = 0.03) were significantly associated with PFS. However, the derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) were not significantly associated with PFS (p-values > 0.15). In the OS analysis, albumin and PNI were the only statistically significant factors in the multivariable model (p < 0.001). CONCLUSIONS: In our cohort, PNI and ECOG performance status were most strongly associated with PFS in R/M HNSCC patients treated with immunotherapy. These results suggest that parameters informative of nutritional status should be considered before immunotherapy.

Update in collecting duct carcinoma: Current aspects of the clinical and molecular characterization of an orphan disease.

Collecting duct renal cell carcinoma (cdRCC), which until recently was thought to arise from the collecting ducts of Bellini in the renal medulla, is a rare and aggressive type of non-clear renal cell carcinoma (ncRCC), accounting for 1% of all renal tumors and with nearly 50% of patients being diagnosed with Stage IV disease. The median overall survival in this setting is less than 12 months. Several regimens of chemotherapies had been used based on morphologic and cytogenetic similarities with urothelial cell carcinoma described previously, although the prognosis still remains poor. The use of targeted therapies also did not result in favorable outcomes. Recent works using NGS have highlighted genomic alterations in SETD2, CDKN2A, SMARCB1, and NF2. Moreover, transcriptomic studies have confirmed the differences between urothelial carcinoma and cdRCC, the possible true origin of this disease in the distal convoluted tubule (DCT), differentiating from other RCC (e.g., clear cell and papillary) that derive from the proximal convoluted tubule (PCT), and enrichment in immune cells that may harbor insights in novel treatment strategies with immunotherapy and target agents. In this review, we update the current aspects of the clinical, molecular characterization, and new targeted therapeutic options for Collecting duct carcinoma and highlight the future perspectives of treatment in this setting.

Efficacy of chemotherapy for malignant pleural mesothelioma according to histology in a real-world cohort.

CheckMate 743 trial demonstrated survival benefit of immunotherapy in first line in MPM with some differences in the efficacy of chemotherapy according to histology. The objective of this study is to characterize the impact of chemotherapy according to histology in patients diagnosed with MPM at our institution. Clinical records of all MPM patients diagnosed at Vall d'Hebron University Hospital between November 2002 and April 2020 were reviewed. Associations between clinical variables and outcomes were assessed with Cox regression models. Survival data were calculated by the Kaplan-Meier method. 189 patients were included with 76% of tumors classified as epithelioid subtype. First line chemotherapy was offered to 85% of patients. Median survival in overall population was 21.3 months (95% CI 17.2-24.3). We found that patients with epithelioid tumors had better overall survival (OS) and progression free survival (PFS). Median OS of epithelioid patients treated with first line chemotherapy was 26.7 months versus 15.0 months in non-epithelioid patients (HR 2.25 CI 95% 1.4-3.4; p < 0.001). Median PFS for patients with epithelioid tumors treated with chemotherapy was 4.8 months versus 3.6 months in non-epithelioid (HR 1.5 CI 95% 1.0-2.3; p = 0.03). The improvement of outcomes in patients with epithelioid histology was detected in patients treated with cisplatin or carboplatin. Histology was not a predictive factor for the platinum agent sensitivity (p of interaction PFS = 0.09, p of interaction OS = 0.65). In our series, patients with non-epithelioid tumors presented worse prognosis. Although epithelioid tumors exposed to cisplatin had higher PFS, histology was not a clear predictor of chemotherapy efficacy.

Overview of hereditary breast and ovarian cancer (HBOC) guidelines across Europe.

Hereditary breast and ovarian cancer (HBOC) is a syndrome defined by an increased risk of developing breast and/or ovarian cancer most commonly due to germline disease-causing variants in the BRCA1 and BRCA2 genes, but also other causative genes such as PALB2, ATM and CHEK2. As genetic testing becomes more prevalent and new clinical data emerge, updates of national guidelines are required to incorporate these advances in our knowledge. The aim of this work is to review the guidelines for HBOC genetic testing and clinical surveillance across European countries, mostly affiliated to the European Reference Network (ERN) for Genetic Tumor Risk Syndroms (GENTURIS). Young onset breast cancer (BC), triple negative phenotype, or bilateral BC are considered as criteria for genetic testing in all, with differences in age limits. Testing of invasive epithelial non-mucinous ovarian cancer is also universally accepted. While breast magnetic resonance imaging (MRI) is consistently recommended in high-risk individuals, age of onset for mammograms differ between 30 and 40 years. Risk-reducing mastectomy is commonly offered as an option, while risk-reducing salpingo-oophorectomy is universally recommended. The largest differences are observed with respect to ovarian surveillance prior to risk-reducing salpingo-oophorectomy and in breast surveillance for carriers of non-BRCA1/2 genes. These differences in national guidelines reflect the variations in clinical consensus that may be reached in the absence of consistent evidence for some recommendations.

Interrelations between Patients' Clinicopathological Characteristics and Their Association with Response to Immunotherapy in a Real-World Cohort of NSCLC Patients.

Immune checkpoint inhibitors (ICIs) have transformed non-small cell lung cancer (NSCLC) treatment. Unfortunately, only some patients benefit from these therapies. Thus, certain clinicopathological characteristics of the patients have been proposed as biomarkers of ICIs response. We assembled a retrospective cohort of 262 NSCLC patients treated with ICIs, compiled relevant clinicopathological characteristics, and studied their associations with treatment outcome using Cox proportional-hazards survival models. Additionally, we investigated the interrelations between clinicopathological features and devised a method to create a compendium associated with ICIs response by selecting those that provide non-redundant information. In multivariate analyses, ECOG performance status (hazard ratio (HR) 1.37 (95% CI 1.11 to 1.68), p < 0.005), LDH (HR 1.24 (95% CI 1.03 to 1.48), p = 0.02)) and PD-L1 negativity were associated with decreased PFS (HR 1.92 (95% CI 1.03 to 3.58), p < 0.04), whereas presentation of immune-related adverse events (irAEs) (HR 0.35 (95% CI 0.22 to 0.55, p < 0.005) or females (HR 0.52 (95% CI 0.33 to 0.80, p < 0.005) had longer progression-free survival. Additionally, numerous clinicopathological indicators were found to be interrelated. Thus, we searched for features that provide non-redundant information, and found the combination of LDH levels, irAEs, and gender to have a better association with ICIs treatment response (cross-validated c-index = 0.66). We concluded that several clinicopathological features showed prognostic value in our real-world cohort. However, some are interrelated, and compendiums of features should therefore consider these interactions. Joint assessment of LDH, irAEs, and gender may be a good prognostic compendium.

Up-to-date role of aflibercept in the treatment of colorectal cancer.

Introduction: Colorectal cancer (CRC) is a major public health problem. Despite major progress understanding the biological basis of this tumor added to the incorporation of optimized diagnostic and therapeutic strategies, prognosis after progression on first-line standard treatment remains poor. Several antiangiogenic treatments have demonstrated improvement in overall survival (OS) in the second-line treatment being aflibercept, a fully humanized recombinant protein, one of them. The results of the VELOUR study showed that the addition of aflibercept to second-line FOLFIRI improved OS and progression-free survival.Areas covered: A literature review of published clinical studies was performed in order to discuss the clinical data on aflibercept in mCRC from early drug development to real-world data.Expert opinion: The combination of aflibercept with FOLFIRI provides a statistical improvement in OS and in all the efficacy endpoints analyzed in the VELOUR trial, showing efficacy independently on time to progression, molecular status, prior biological treatment, or age. Further studies are needed to find new biomarkers and molecular characterization in order to better select patients that could benefit from this treatment.

Grade I meningioma with disseminated bone disease: a rare clinical phenomenon.

Meningioma, the second most common primary tumour of the central nervous system, is classified into three different grades based on their characteristics. Each tumour grade includes different molecular subtype, growth potential, and thus, different prognosis. Grade I meningioma is the most common subtype with a benign course, in which systemic dissemination rarely occurs. We present the case of a 48-year-old male patient with a history of grade I meningioma who was referred 3 years after the initial diagnosis to our centre due to pelvic pain. Computed tomography (CT) images showed new pelvic bone lesions whose histopathological report was compatible with a grade I meningioma. Neither hormonal therapy concomitant with octreotide nor hydroxiurea treatments were effective. Very little is known about this entity's prevalence and treatment when disseminated disease occurs. Thus, we think it is important to increase the positive and negative clinical experiences in this setting.