Impact of cemiplimab treatment duration on clinical outcomes in advanced cutaneous squamous cell carcinoma.

Treatment duration with checkpoint inhibitors must be optimized to prevent unjustified toxicity, but evidence for the management of cutaneous squamous cell carcinoma is lacking. A retrospective study was performed to evaluate the survival of patients with cutaneous squamous cell carcinoma (CSCC) who discontinued cemiplimab due to different causes and without progression. Among 95 patients with CSCC who received cemiplimab, 22 (23%) patients discontinued immunotherapy due to causes other than progression, such as comorbidities, toxicity, complete response or lack of compliance (group that discontinued before censoring [DBC]), then 73 patients had standard treatment scheduled (STS). The overall survival was 25.2 months (95% CI: 8.9-29.4) in STS group and 28.3 months (95% CI: 12.7-28.3) in the DBC group; deaths for all causes were 11/22 (50%) in the DBC group and 34/73 (46.6%) in the STS group (p = 0.32). 10/22 (45.4%) subjects died due to CSCC in the DBC after discontinuation and 34/73 (46.6%) in the STS group, and the difference between groups was not significant (p = 0.230). Duration of treatment was significantly lower in subjects with stable disease versus those with complete or partial response (16.9, 30.6 and 34.9 months, respectively; p = 0.004). Among the 22 STS patients, 12 received cemiplimab for less than 12 months (10 [83%] died) and 10 for at least 12 months (1 [10%] died). Our observation, finding no outcome difference between DBC and STS groups, suggests that ICI treatment after one year might expose patients to further treatment related events without efficacy advantages.

Exploring the potential of multiomics liquid biopsy testing in the clinical setting of lung cancer.

The transformative role of artificial intelligence (AI) and multiomics could enhance the diagnostic and prognostic capabilities of liquid biopsy (LB) for lung cancer (LC). Despite advances, the transition from tissue biopsies to more sophisticated, non-invasive methods like LB has been impeded by challenges such as the heterogeneity of biomarkers and the low concentration of tumour-related analytes. The advent of multiomics - enabled by deep learning algorithms - offers a solution by allowing the simultaneous analysis of various analytes across multiple biological fluids, presenting a paradigm shift in cancer diagnostics. Through multi-marker, multi-analyte and multi-source approaches, this review showcases how AI and multiomics are identifying clinically valuable biomarker combinations that correlate with patients' health statuses. However, the path towards clinical implementation is fraught with challenges, including study reproducibility and lack of methodological standardization, thus necessitating urgent solutions to solve these common issues.

Homologous Recombination Repair Deficiency in Metastatic Prostate Cancer: New Therapeutic Opportunities.

More than 20% of metastatic prostate cancer carries genomic defects involving DNA damage repair pathways, mainly in homologous recombination repair-related genes. The recent approval of olaparib has paved the way to precision medicine for the treatment of metastatic prostate cancer with PARP inhibitors in this subset of patients, especially in the case of BRCA1 or BRCA2 pathogenic/likely pathogenic variants. In face of this new therapeutic opportunity, many issues remain unsolved. This narrative review aims to describe the relationship between homologous recombination repair deficiency and prostate cancer, the techniques used to determine homologous recombination repair status in prostate cancer, the crosstalk between homologous recombination repair and the androgen receptor pathway, the current evidence on PARP inhibitors activity in metastatic prostate cancer also in homologous recombination repair-proficient tumors, as well as emerging mechanisms of resistance to PARP inhibitors. The possibility of combination therapies including a PARP inhibitor is an attractive option, and more robust data are awaited from ongoing phase II and phase III trials outlined in this manuscript.

Real-World Impact of Upfront Cytoreductive Nephrectomy in Metastatic Non-Clear Cell Renal Cell Carcinoma Treated with First-Line Immunotherapy Combinations or Tyrosine Kinase Inhibitors (A Sub-Analysis from the ARON-1 Retrospective Study).

BACKGROUND: About 20% of patients with renal cell carcinoma present with non-clear cell histology (nccRCC), encompassing various histological types. While surgery remains pivotal for localized-stage nccRCC, the role of cytoreductive nephrectomy (CN) in metastatic nccRCC is contentious. Limited data exist on the role of CN in metastatic nccRCC under current standard of care. OBJECTIVE: This retrospective study focused on the impact of upfront CN on metastatic nccRCC outcomes with first-line immune checkpoint inhibitor (IO) combinations or tyrosine kinase inhibitor (TKI) monotherapy. METHODS: The study included 221 patients with nccRCC and synchronous metastatic disease, treated with IO combinations or TKI monotherapy in the first line. Baseline clinical characteristics, systemic therapy, and treatment outcomes were analyzed. The primary objective was to assess clinical outcomes, including progression-free survival (PFS) and overall survival (OS). Statistical analysis involved the Fisher exact test, Pearson's correlation coefficient, analysis of variance, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. RESULTS: Median OS for patients undergoing upfront CN was 36.8 (95% confidence interval [CI] 24.9-71.3) versus 20.8 (95% CI 12.6-24.8) months for those without CN (p = 0.005). Upfront CN was significantly associated with OS in the multivariate Cox regression analysis (hazard ratio 0.47 [95% CI 0.31-0.72], p < 0.001). In patients without CN, the median OS and PFS was 24.5 (95% CI 18.1-40.5) and 13.0 months (95% CI 6.6-23.5) for patients treated with IO+TKI versus 7.5 (95% CI 4.3-22.4) and 4.9 months (95% CI 3.0-8.1) for those receiving the IO+IO combination (p = 0.059 and p = 0.032, respectively). CONCLUSIONS: Our study demonstrates the survival benefits of upfront CN compared with systemic therapy without CN. The study suggests that the use of IO+TKI combination or, eventually, TKI monotherapy might be a better choice than IO+IO combination for patients who are not candidates for CN regardless of IO eligibility. Prospective trials are needed to validate these findings and refine the role of CN in current mRCC management.

Assessing the effectiveness and safety of lenvatinib and everolimus in advanced renal cell carcinoma: insights from the RELIEVE study's analysis of heavily pretreated patients.

Background: The treatment of heavily pretreated patients with metastatic renal cell carcinoma (mRCC) represents an unmet medical need and is still challenging. Objectives: The primary objective was to assess the effectiveness of the lenvatinib plus everolimus combination and the secondary objective was the toxicity profile of this combination. Design: We conducted a longitudinal retrospective study examining mRCC patients pre-treated with one or more lines of therapy among different cancer centers in Italy. Methods: The study included patients who received the combination of lenvatinib plus everolimus as either a second-line treatment or beyond. We assessed progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), response rate (RR), and toxicity profile. In addition, we explored the potential relationship between treatment effectiveness and clinical and laboratory parameters. Results: In all, 33 patients were assessed, the median age was 60 years, 57% had an Eastern Cooperative Oncology Group performance status of 1-2 and. 63% received ⩾ 3 prior lines of therapy. 62% were 'intermediate risk' according to the International Metastatic Renal Cell Carcinoma Database Consortium and 30% were 'poor risk'. The RR was 42% (no complete response), 18% stable disease. Median OS was 11.2 months (95% CI 6.8-19.9), median PFS was 6.7 months (95% CI 0.6-30.8), and median TTF was 6.7 months (95% CI 4.8-16.6). A shorter OS was significantly associated with lymph node metastases (p = 0.043, 95% CI), neutrophils/ lymphocytes ratio (NLR) ⩾ 3 (p = 0.007), hemoglobin/red cell distribution width ratio cutoff value <0.7 was significant (p = 0.03) while a shorter PFS was associated with lung (p = 0.048) and brain metastases (p = 0.023). The most frequent G1 toxicity was diarrhea (24%), G2 was fatigue (30%), and hypertension and skin toxicity (6%) for G3. Conclusion: Our findings suggest a clinically relevant effectiveness of lenvatinib plus everolimus combination with an acceptable toxicity profile for heavily pretreated patients with mRCC.

Indicators of cure for women living after uterine and ovarian cancers: a population-based study.

This study aims to estimate long-term survival, cancer prevalence, and several cure indicators for Italian women with gynaecological cancers. Thirty-one cancer registries, representing 47% of the Italian female population, were included. Mixture cure models were used to estimate Net Survival (NS), Cure Fraction, Time To Cure (5-year conditional NS>95%), Cure Prevalence (women who will not die of cancer), and Already Cured (living longer than Time to Cure). In 2018, 0.4% (121,704) of Italian women were alive after corpus uteri cancer, 0.2% (52,551) after cervical, and 0.2% (52,153) after ovarian cancer. More than 90% of patients with uterine cancers and 83% with ovarian cancer will not die from their neoplasm (Cure Prevalence). Women with gynaecological cancers have a residual excess risk of death <5% after 5 years since diagnosis. The Cure Fraction was 69% for corpus uteri, 32% for ovarian, and 58% for cervical cancer patients. Time To Cure was ≤10 years for women with gynaecological cancers aged <55 years. 74% of patients with cervical cancer, 63% with corpus uteri cancer, and 55% with ovarian cancer were Already Cured. These results will contribute to improving follow-up programs for women with gynaecological cancers and supporting efforts against discrimination of already cured ones.

Potential role of SIRT-1 and SIRT-3 as biomarkers for the diagnosis and prognosis of idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a debilitating and progressive lung disease of unknown aetiology, characterized by the relentless deposition of fibrotic tissue. Biomarkers may play a pivotal role as indicators of disease presence, progression, and treatment response. Sirtuins, a family of enzymes with ADP ribosyltransferase or deacetylase activity, have been implicated in several diseases, including pulmonary fibrosis. METHODS: A cross-sectional, prospective, observational single-center study was conducted to investigate the potential role of serum SIRTs levels as biomarkers in patients with IPF. Demographic, clinical, and functional data and serological samples were collected from 34 patients with IPF followed at the Interstital Lung and Rare Diseases Outpatient Clinic of the Vanvitelli Pneumology Clinic, Monaldi Hospital, Naples, Italy and from 19 age-matched controls. RESULTS: Serum SIRT-1 levels were significantly reduced in IPF patients compared to controls (median IPF 667 [435-858] pg/mL versus controls 925 [794-1173] pg/mL; p < 0.001 ). In contrast, serum SIRT-3 levels were significantly increased in IPF patients compared to controls (median IPF 338 [230-500] pg/mL versus controls 154 [99.8-246] pg/mL; p < 0.001). There were no statistically significant differences in serum SIRT-6 and SIRT-7 levels between IPF and controls. In addition, we found a significant positive correlation between SIRT-1 and lung function parameters such as FEV1% (ϱ=0.417;p = 0.016), FVC% (ϱ=0.449;p = 0.009) and DLCO% (ϱ=0.393;p = 0.024), while a significant negative correlation was demonstrated between SIR-1 and GAP score, demonstrating a significant reduction in SIRT-1 in advanced Gender-Age-Physiology (GAP) stages 2-3 compared to GAP stage 1 (p = 0.008). CONCLUSIONS: This prospective, cross-sectional study showed that SIRT-1 was associated with lung function and IPF severity and that both SIRT-1 and SIRT-3 could be considered as potential biomarkers of IPF, whereas SIRT-6 and SIRT-7 were not associated with IPF.

Pembrolizumab in Vaginal Carcinoma: A Case Report and Review of the Literature.

Introduction: Vaginal cancer is a rare gynecologic malignancy. While in a localized disease, concurrent chemoradiation grants local control and better overall survival, in a metastatic setting, the management options are very limited. Furthermore, recurrent cervical, vulvar, and vaginal carcinomas notoriously develop resistance to treatment, and consequently, their prognosis is still poor. Case Presentation: We herein present the case of a woman with a nodal relapse of vaginal carcinoma, effectively treated with third-line immunotherapy. We will also provide a review of the literature on the new therapeutic strategies for advanced vaginal carcinoma, with a focus on pembrolizumab immunotherapy. Conclusion: Pembrolizumab might represent a promising option for the management of vaginal and vulvar cancer, but data to support its use in this setting are still lacking. This case highlights the need for further investigation and trial designs for this rare disease.

Clinical Outcomes and Prognostic Factors in Patients With Penile Carcinoma: A Sub-Analysis From Meet-URO 23 (I-RARE) Registry Study.

INTRODUCTION: Penile squamous cell carcinoma (PSCC) is a rare tumor with an aggressive behavior. The Meet-URO 23/I-RARE registry includes rare genitourinary malignancies. We extracted patients with PSCC to conduct a retrospective study aimed at assessing clinical outcomes and prognostic factors. PATIENTS AND METHODS: Primary endpoints were overall survival and progression-free survival. Prognostic factors for OS and PFS were analyzed using univariate and multivariate analysis. From the Meet-URO 23/I-RARE database, we extracted 128 patients with diagnosis of PSCC. About 48% of patients underwent first-line of therapy. RESULTS: In the overall population, median OS from diagnosis was 34.6 months. Significant differences in median OS were observed according to ECOG PS at diagnosis (57.3 months vs. 8.3 months; P < .001), and median age (≤77y 88.8 months vs. >77y 26 months; P = .013). At multivariate analysis, ECOG PS 2-4 at diagnosis (HR 3.04) and lymph node metastases (HR 2.49) were independently associated with a higher risk of death. Among patients undergoing first-line therapy (n = 61), median OS was 12.3 months, and a statistically significant difference was found according to type of response to first-line (DCR 24.4 months vs. PD 7.1 months; P < .001). Multivariate analysis showed that only age >77 years was associated with a worse OS (HR 2.16). A statistically significant difference in PFS was found according to platinum plus 5-fluorouracil versus platinum plus taxane (4.9 vs. 3.4 months; P = .036) and regimens with 2 versus 3 drugs (3.4 vs. 8.6 months; P = .019). At the multivariate analysis only regimens with platinum plus taxane were associated with worse PFS (HR 2.83). CONCLUSION: In our registry study, PSCC is confirmed to be an aggressive disease. Poor ECOG PS, presence of lymph node metastases, and higher age at diagnosis appear to be associated with worse survival outcomes.

Papillary Renal Cell Carcinoma: Outcomes for Patients Receiving First-line Immune-based Combinations or Tyrosine Kinase Inhibitors from the ARON-1 Study.

BACKGROUND AND OBJECTIVE: Papillary renal cell carcinoma (pRCC) is the most frequent histological subtype of non-clear cell RCC (nccRCC). Owing to the heterogeneity of nccRCC, patients are often excluded from large phase 3 trials focused on clear cell RCC, so treatment options for nccRCC remain limited. Our aim was to investigate the efficacy of first-line treatment with tyrosine kinase inhibitors (TKIs) or immuno-oncology (IO)-based combinations in patients with pRCC. METHODS: We performed a multicenter retrospective analysis of real-world data collected for patients with advanced pRCC treated in 40 centers in 12 countries as part of the ARON-1 project (NCT05287464). The primary endpoints were overall survival (OS), progression-free survival (PFS), the overall response rate (ORR), and time to second progression (PFS2). OS, PFS, and PFS2 were estimated using the Kaplan-Meier method and results were compared between the treatment groups using a log-rank test. Univariate and multivariable analyses were carried out using Cox proportional-hazard models. KEY FINDINGS AND LIMITATIONS: We included 200 patients with metastatic pRCC, of whom 73 were treated with IO-based combinations and 127 with TKIs. Median OS was 22.5 mo in the TKI group 28.8 mo in the IO group (p = 0.081). Median PFS was 6.4 mo in the TKI group and 17.4 mo in the IO group (p < 0.001). The ORR was higher in the IO group than in the TKI group (41% vs 27%; p = 0.037). CONCLUSIONS AND CLINICAL IMPLICATIONS: Our results show that IO-based combinations have superior efficacy outcomes to TKIs for first-line treatment of metastatic pRCC. PATIENT SUMMARY: The ARON-1 project collects clinical data for patients with kidney cancer treated in multiple centers worldwide to assess outcomes in the real-world setting. We analyzed data for patients with metastatic kidney cancer of a specific subtype to evaluate the efficacy of different first-line treatments. Patients treated with immune-based combinations had better outcomes than patients treated with tyrosine kinase inhibitors.

Molecular characterization as new driver in prognostic signatures and therapeutic strategies for endometrial cancer.

Endometrial cancer (EC) incidence and mortality rates have been increasing, particularly among young females. Although more than 90% of ECs are sporadic, 5-10% are hereditary, a majority of which occurs within Hereditary Non-Polyposis Colorectal Cancer syndrome (HNPCC) or Lynch syndrome. The traditional histopathological classification differentiates EC between two main groups: type I (or endometrioid) and type II (including all other histopathological subtypes). However, this classification lacks reproducibility and does not account for the emerging molecular heterogeneity. In 2013, The Cancer Genome Atlas (TCGA) project proposed EC molecular classification defining four groups with different prognostic and predictive values and the current international guidelines are progressively establishing EC risk stratification and treatment based on both histopathological and molecular criteria. Our manuscript aims to summarize the current state of EC molecular characterizations, including germline alterations at the basis of hereditary EC predisposition, to discuss their clinical utility as prognostic and predictive markers.

Cure indicators and prevalence by stage at diagnosis for breast and colorectal cancer patients: A population-based study in Italy.

People alive many years after breast (BC) or colorectal cancer (CRC) diagnoses are increasing. This paper aimed to estimate the indicators of cancer cure and complete prevalence for Italian patients with BC and CRC by stage and age. A total of 31 Italian Cancer Registries (47% of the population) data until 2017 were included. Mixture cure models allowed estimation of net survival (NS); cure fraction (CF); time to cure (TTC, 5-year conditional NS >95%); cure prevalence (who will not die of cancer); and already cured (prevalent patients living longer than TTC). 2.6% of all Italian women (806,410) were alive in 2018 after BC and 88% will not die of BC. For those diagnosed in 2010, CF was 73%, 99% when diagnosed at stage I, 81% at stage II, and 36% at stages III-IV. For all stages combined, TTC was >10 years under 45 and over 65 years and for women with advanced stages, but ≤1 year for all BC patients at stage I. The proportion of already cured prevalent BC women was 75% (94% at stage I). Prevalent CRC cases were 422,407 (0.7% of the Italian population), 90% will not die of CRC. For CRC patients, CF was 56%, 92% at stage I, 71% at stage II, and 35% at stages III-IV. TTC was ≤10 years for all age groups and stages. Already cured were 59% of all prevalent CRC patients (93% at stage I). Cancer cure indicators by stage may contribute to appropriate follow-up in the years after diagnosis, thus avoiding patients' discrimination.

Comparative Study of Mycobacterium bovis and Mycobacterium avium subsp. paratuberculosis In Vitro Infection in Bovine Bone Marrow Derived Macrophages: Preliminary Results.

Bovine tuberculosis and paratuberculosis are endemic in many areas worldwide. This work aims to study cytokines production and gene expression profiles of bovine macrophages infected with Mycobacterium bovis and Mycobacterium paratuberculosis subsp. avium (MAP) strains to identify potential diagnostic biomarkers. Bovine bone marrow stem cells were differentiated into macrophages and subsequently infected in vitro with different spoligotypes of M. bovis and MAP field strains (as single infections and coinfections), using different multiplicity of infection. Supernatant and cell pellets were collected 24 h, 48 h, and one week post-infection. Preliminarily, gene expression on cell pellets of IL-1ß, IL-2, INFγ, IL-6, IL-10, IL-12, and TNFα was assessed by qRT-PCR one week p.i. Subsequently, IL-1ß and IL-6 were measured by ELISA and qRT-PCR to investigated their production retrospectively 24 h and 48 h p.i. A variability in macrophages response related to the concentration of mycobacteria, the coinfection with MAP, and M. bovis spoligotypes was identified. An early and constant IL-6 increase was observed in the M. bovis infection. A lower increase in IL-1ß was also detected at the highest concentration of the two M. bovis spoligotypes one week post-infection. IL-6 and IL-1 ß production was reduced and differently expressed in the MAP infection. IL-6 appeared to be the earliest cytokines produced by bovine macrophages infected with M. bovis.

Combined immunotherapy in melanoma patients with brain metastases: A multicenter international study.

BACKGROUND: Ipilimumab plus nivolumab (COMBO) is the standard treatment in asymptomatic patients with melanoma brain metastases (MBM). We report a retrospective study aiming to assess the outcome of patients with MBM treated with COMBO outside clinical trials. METHODS: Consecutive patients treated with COMBO have been included. Demographics, steroid treatment, Central Nervous System (CNS)-related symptoms, BRAF status, radiotherapy or surgery, response rate (RR), progression-free (PFS) and overall survival (OS) have been analyzed. RESULTS: 376 patients were included: 262 received COMBO as first-line and 114 as a subsequent line of therapy, respectively. In multivariate analysis, Eastern Cooperative Oncology Group (ECOG) (≥1 vs 0) [HR 1.97 (1.46-2.66)], extracerebral metastases [HR 1.92 (1.09-3.40)], steroid use at the start of COMBO [HR 1.59 (1.08-2.38)], CNS-related symptoms [HR 1.59 (1.08-2.34)], SRS (Stereotactic radiosurgery) [HR 0.63 (0.45-0.88)] and surgery [HR 0.63 (0.43-0.91)] were associated with OS. At a median follow-up of 30 months, the median OS (mOS) in the overall population was 21.3 months (18.1-24.5), whilst OS was not yet reached in treatment-naive patients, steroid-free at baseline. In patients receiving COMBO after BRAF/MEK inhibitors(i) PFS at 1-year was 15.7%. The dose of steroids (dexamethasone < vs ≥ 4 mg/day) was not prognostic. SRS alongside COMBO vs COMBO alone in asymptomatic patients prolonged survival. (p = 0.013). Toxicities were consistent with previous studies. An independent validation cohort (n = 51) confirmed the findings. CONCLUSIONS: Our results demonstrate remarkable long-term survival in treatment-naïve, asymptomatic, steroid-free patients, as well as in those receiving SRS plus COMBO. PFS and OS were poor in patients receiving COMBO after progressing to BRAF/MEKi.

Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial.

No prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBIT (NCT02631447) was a randomized, three-arm, noncomparative phase II trial in which patients were randomized to one of two sequences with immunotherapy or targeted therapy first, with a third arm in which an 8-week induction course of targeted therapy followed by a planned switch to immunotherapy was the first treatment. BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. Primary outcome of overall survival was previously reported, demonstrating improved survival with immunotherapy administered until progression and followed by BRAF/MEK inhibition. Here we report 4-year survival outcomes, confirming long-term benefit with first-line immunotherapy. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy.

Primary neuroendocrine neoplasms of the vulva: A review of the MITO rare cancer group.

Gynecological neuroendocrine neoplasms are rare entities and can be divided into two groups: carcinoids and neuroendocrine carcinomas. Due to their rarity their management is not standardized. The aim of this work is to summarize and discuss the current literature evidence on this pathology. A scoping literature review was performed in multiple databases. Thirty-one studies were included: 30 case reports and one case series. Patients' age ranged between 28 and 92 years. Surgery was the most used treatment and the surgical approach included local excision (N = 16/31; 51.6%) with (N = 5/16; 31.25%) or without (N = 11/16; 68.75%) inguinal lymphadenectomy. Adjuvant radiotherapy was delivered in 12 (38.7%) cases; instead, platinum-based therapies were frequently used when chemotherapy was chosen for adjuvant treatment. The overall survival ranged between 20 days to 4 years. However, further research is needed; currently, multimodal approach including surgery, chemotherapy and radiotherapy appeared safe and feasible for the treatment of these rare and aggressive diseases.

Cerebellar metastasis of ovarian cancer: a case report.

BACKGROUND: Ovarian cancer is metastatic at presentation in about 62% of cases, but brain metastases are rare, reported in 3.3-4% of patients. Brain metastasis seems to be more frequent in advanced stages at diagnosis and in patients with BRCA1/2 mutation. CASE PRESENTATION: We present a case of a 47-year-old Caucasian woman, BRCA wild type, with an ovarian cancer that started with single cerebellar metastasis. CONCLUSION: Brain metastases in ovarian cancer are rare and complex for diagnosis and management. This case focuses both on diagnosis and treatment, emphasizing the importance of a multimodal approach in a multidisciplinary team.

De Novo Metastatic Prostate Cancer: Are We Moving toward a Personalized Treatment?

De novo metastatic hormone-sensitive PC (mHSPC) accounts for 5-10% of all prostate cancer (PC) diagnoses but it is responsible for nearly 50% of PC-related deaths. Since 2015, the prognosis of mHSPC has slightly improved thanks to the introduction of new hormonal agents and chemotherapy combined with androgen deprivation therapy from the first-line setting. This review describes the current therapeutic opportunities for de novo mHSPC, focusing on potential molecular biomarkers identified in the main clinical trials that have modified the standard of care, the genomic features of de novo mHSPC, and the principal ongoing trials that are investigating new therapeutic approaches and the efficacy of a biomarker-guided treatment in this setting. The road toward personalized treatment for de novo mHSPC is still long, considering that the randomized clinical trials, which have furnished the basis of the current therapeutic options, stratified patients according to clinical criteria that did not necessarily reflect the biological rationale of the chosen therapy. The role of transcriptomic profiling of mHSPC as a predictive biomarker requires further validation, and it remains to be ascertained how the genomic variants detected in mHSPC, which are regarded as predictive in the castration-resistant disease, can be exploited in the mHSPC setting.

Cancer and Pregnancy: Estimates in Italy from Record-Linkage Procedures between Cancer Registries and the Hospital Discharge Database.

The aim of this study is to describe the frequency and trend of pregnancy-associated cancer (PAC) in Italy, an increasingly relevant phenomenon due to postponing age at childbirth. To this purpose, a population-based retrospective longitudinal study design based on cohorts of women aged 15-49 diagnosed with cancer and concomitant pregnancy is proposed. The study uses 19 population-based Cancer Registries, covering about 22% of Italy, and linked at an individual level with Hospital Discharge Records. A total of 2,861,437 pregnancies and 3559 PAC are identified from 74,165 women of the cohort with a rate of 1.24 PAC per 1000 pregnancies. The most frequent cancer site is breast (24.3%), followed by thyroid (23.9%) and melanoma (14.3%). The most frequent outcome is delivery (53.1%), followed by voluntary termination of pregnancy and spontaneous abortion (both 12.0%). The trend of PAC increased from 2003 to 2015, especially when the outcome is delivery, thus confirming a new attitude of clinicians to manage cancer throughout pregnancy. This represents the first attempt in Italy to describe PAC from Cancer Registries data; the methodology is applicable to other areas with the same data availability. Evidence from this study is addressed to clinicians for improving clinical management of women with PAC.

Bifidobacterium affects antitumor efficacy of oncolytic adenovirus in a mouse model of melanoma.

Gut microbiota plays a key role in modulating responses to cancer immunotherapy in melanoma patients. Oncolytic viruses (OVs) represent emerging tools in cancer therapy, inducing a potent immunogenic cancer cell death (ICD) and recruiting immune cells in tumors, poorly infiltrated by T cells. We investigated whether the antitumoral activity of oncolytic adenovirus Ad5D24-CpG (Ad-CpG) was gut microbiota-mediated in a syngeneic mouse model of melanoma and observed that ICD was weakened by vancomycin-mediated perturbation of gut microbiota. Ad-CpG efficacy was increased by oral supplementation with Bifidobacterium, reducing melanoma progression and tumor-infiltrating regulatory T cells. Fecal microbiota was enriched in bacterial species belonging to the Firmicutes phylum in mice treated with both Bifidobacterium and Ad-CpG; furthermore, our data suggest that molecular mimicry between melanoma and Bifidobacterium-derived epitopes may favor activation of cross-reactive T cells and constitutes one of the mechanisms by which gut microbiota modulates OVs response.