Research Protocol for an Observational Health Data Analysis on the Adverse Events of Systemic Treatment in Patients with Metastatic Hormone-sensitive Prostate Cancer: Big Data Analytics Using the PIONEER Platform.

Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in "real-life" patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.

Complications Associated with Facial Autologous Fat Grafting for Aesthetic Purposes: A Systematic Review of the Literature.

Background: With the increasing demand for aesthetic procedures, autologous fat grafting (AFG) seems to be an attractive option for facial volumization and rejuvenation. The aim of this study was to assess the type and severity of associated complications after facial AFG for aesthetic purposes. Methods: The entire PubMed/Medline and Cochrane databases were screened to identify studies describing complications that occurred after the injection of autologous fat into the face. These complications have been reviewed and analyzed according to their occurrence and severity in the different anatomical regions of the face. Results: Twenty-two articles including 38 patients reported on a total of 58 complications. Thirty-two complications have been classified as severe or permanent, including hemiplegia (n = 11), loss of vision (n = 7), or skin necrosis (n = 3). The other 26 complications were classified as mild or transient, such as lipogranuloma (n = 12) or mycobacterial abscess (n = 2). The majority of complications were reported after injection to the forehead (n = 26) and the temporal region (n = 21). Interestingly, this location seems to be the area at risk because 53% of all severe complications occurred in this anatomical region. Conclusions: AFG to the face is associated with a low incidence of complications, but if they occur, they can be dramatic, particularly in the forehead and temporal region. Nevertheless, AFG can be used to correct age-related changes of the face and volume loss and may represent an alternative to synthetic fillers. Therefore, AFG to the face should be performed by qualified doctors under careful consideration of risks and facial anatomy.

Fat Body Mass and Vertebral Fracture Progression in Women With Breast Cancer.

Importance: Women with early breast cancer (EBC) exposed to aromatase inhibitors (AIs) may experience fragility fractures despite treatment with bone-active drugs. Risk factors for fractures in patients receiving AIs and denosumab have not been explored to date. Objectives: To evaluate whether an association exists between dual x-ray absorptiometry (DXA)-measured fat body mass (FBM) and vertebral fracture (VF) progression in postmenopausal women with EBC undergoing adjuvant therapy with AIs in combination with denosumab and to examine whether VF was associated with common risk factors for bone fracture and parameters of body composition other than FBM. Design, Setting, and Participants: For this prospective, single-center, cohort study, 237 patients with EBC who were undergoing adjuvant treatment with AIs and denosumab (60 mg every 6 months) were enrolled at the Breast Unit of the ASST Spedali Civili of Brescia from September 2014 to June 2018. Data analysis was conducted in June 2022. Exposure: Body composition parameters, bone mineral density, and morphometric VFs were assessed by DXA at study entry and after 18 months of therapy. Main Outcomes and Measures: VF progression, defined as either new or worsening of preexisting VFs, between the 2 time points. Results: Of the 237 patients enrolled (median [range] age, 61 [28-84] years), 17 (4.4%) reported VF progression. Univariable analysis found an association between VF progression and a history of clinical fractures (odds ratio [OR], 3.22; 95% CI, 1.19-8.74; P = .02), Fracture Risk Assessment Tool (FRAX) score for major fractures (OR, 4.42; 95% CI, 1.23-13.79; P = .04), percentage of FBM (OR, 6.04; 95% CI, 1.69-21.63; P = .006), and android fat (OR, 9.58; 95% CI, 1.17-78.21; P = .04) and an inverse association with appendicular lean mass index-FBM ratio (OR, 0.25, 95% CI, 0.08-0.82; P = .02). Multivariable analysis revealed percentage of FBM (OR, 5.41; 95% CI, 1.49-19.59; P = .01) and FRAX score (OR, 3.95; 95% CI, 1.09-14.39; P = .04) as independent variables associated with VF progression. Conclusions and Relevance: The findings of this study suggest that baseline FBM is an independent factor for VF progression in patients with EBC treated with adjuvant AIs and denosumab. This observation is new and indicates that diet and exercise may synergize with denosumab in the management of bone health in this patient setting.

Where do we stand with immunotherapy for nonmelanoma skin cancers in the curative setting?

PURPOSE OF REVIEW: Nonmelanoma skin cancers (NMSC) represent a heterogeneous group of diseases that encompasses among the principal histologies basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC). Given the fact that high tumor mutational burden due to ultraviolet mutagenesis represents a common hallmark of NMSCs, immunotherapy has proved to be a promising therapeutic approach in recent years. The aim of this review is to shed light on immunotherapy applications in NMSCs in the curative setting. RECENT FINDINGS: Immune checkpoint inhibitors represent the first-line treatment of choice for advanced cSCC and MCC, while in second line for BCC. Given this success, more and more trials are evaluating the use of immune checkpoint blockade in neoadjuvant setting for NMSCs. Clinical trials are still ongoing, with the most mature data being found in cSCC. Also, translational studies have identified promising biomarkers of response. SUMMARY: Locoregional treatments of NMSCs can have non negligible functional and cosmetic impacts on patients, affecting their quality of life. As immunogenic diseases, neoadjuvant immunotherapy represents a promising treatment that could change the therapeutic path of these patients. Upcoming results from clinical trials will address these crucial issues.

Morbidity of Transrectal MRI-Fusion Targeted Prostate Biopsy at a Tertiary Referral Academic Centre: An Audit to Guide the Transition to the Transperineal Approach.

Despite transrectal prostate biopsy (TRPB) being still widespread globally, the EAU Guidelines strongly recommend the transperineal approach, due to the reported lower infectious risk. Our study aims to evaluate the impact of a standardized clinical pathway for TRPB on post-operative complications. We prospectively collected data from all patients undergoing mpMRI-targeted TRPB at our Academic Centre from January 2020 to December 2022. All patients followed a standardized, structured multistep pathway. Post-procedural complications were collected and classified according to the Clavien-Dindo (CD) Classification. Among 458 patients, post-procedural adverse events were reported by 203 (44.3%), of which 161 (35.2%) experienced CD grade 1 complications (hematuria [124, 27.1%], hematochezia [22, 4.8%], hematospermia [14, 3.1%], or a combination [20, 4.4%]), and 45 (9.0%) reported CD grade 2 complications (acute urinary retention or hematuria needing catheterization, as well as urinary tract infections, of which 2 cases required hospitalization). No major complications, including sepsis, were observed. At uni- and multivariable analysis, age > 70 years and BMI > 25 kg/ m2 for patients were identified as predictors of post-operative complications. The results of our study confirm that TRPB is a safe and cost-effective procedure with a low risk of severe adverse events in experienced hands and following a standardized pathway.

Plasma EBV DNA as a prognostic factor in EBV associated gastric cancer: a multicenter, prospective study (EBV PRESAGE study).

Purpose: The Cancer Genome Atlas Research Network identified Epstein-Barr-Virus (EBV)-positive gastric cancer as a distinct molecular subtype. The prevalence is 8-9% and the histological examination shows pronounced lymphocytic infiltration, elevated levels of IFN-γ and consequently overexpression of PD-L1. The role of plasma EBV DNA load as a prognostic factor in patients with this cancer subtype is still to be defined. Methods and analysis: The present multicenter prospective observational study "EBV PRESAGE", involving German and Italian cancer centers, aims to evaluate the prognostic role of plasma EBV DNA in EBV-related gastric cancer (GC). The objective is to study the association between plasma EBV DNA load at different consecutive time points and the patient's prognosis. Every patient with a new diagnosis of gastric cancer (including gastroesophageal junction adenocarcinoma) will be screened for Epstein-Barr encoded small Region (EBER) on tissue biopsies using in situ hybridization (ISH). If EBER ISH is positive, blood analysis for plasma EBV DNA will be conducted. The plasma EBV quantitative analysis will be centralized, and extraction, detection, and quantification of EBV DNA in plasma samples will be performed using real-time PCR. Discussion: We hypothesized that plasma EBV DNA represents a non-invasive tool for monitoring EBV-related GC and might be valuable as a prognostic marker.

Advanced Cutaneous Squamous Cell Carcinoma Management in Immunotherapy Era: Achievements and New Challenges.

Introduction of immunotherapy (IT) has radically changed the therapeutic scenario in patients affected by locally advanced and/or metastatic cutaneous squamous cell carcinoma (cSCC) patients. If it is well consolidated the role of immunotherapy in the setting of a disease not amenable to curative surgery and/or radiation, how to integrate immune checkpoint inhibitors in the curative setting is still under evaluation. Surgery combined or not with adjuvant radiotherapy remains the mainstay of curative treatment in localized cSCC; however, promising data with neoadjuvant or perioperative immunotherapy could pave the way towards treatment de-escalation according to the response achieved. On the other side, data on adjuvant treatment with pembrolizumab and cemiplimab after surgery and radiation are still awaited. Several questions related to the activity and the safety of immunotherapy in the real-world setting still remain without answer, and several points need to be better explored. In the current review we will explore the updated literature on the use of immunotherapy in cSCC, and we will show the current challenges in its use.

The Evolving Treatment Landscape of Medullary Thyroid Cancer.

OPINION STATEMENT: Genetic assessment is crucial to address the correct treatment for advanced medullary thyroid cancer (MTC). Multi tyrosine kinase inhibitors (mTKIs) cabozantinib and vandetanib are good first line options, even vandetanib prescription is currently limited to RET mutated patients. Selective RET inhibitors such as pralsetinib could be a preferred upfront treatment in case of RET mutated MTC presenting common or gatekeeper RET mutations (e.g. M918T; V804L/M). Selpercatinib, otherwise, can be prescribed as the second line after disease progression to mTKIs. The best option for subsequent lines is to consider inclusion in clinical trials or alternatively other mTKIs such as sunitinib, sorafenib, lenvatinib, or pazopanib could be evaluated. New perspectives include next-generation RET inhibitors able to overcome resistance mechanisms responsible for disease progression to standard mTKIs and RET inhibitors, and immunotherapy for MTC presenting with high tumor mutational burden.

Feasibility and Activity of Megestrol Acetate in Addition to Etoposide, Doxorubicin, Cisplatin, and Mitotane as First-Line Therapy in Patients with Metastatic/Unresectable Adrenocortical Carcinoma with Low Performance Status.

(1) Background: The standard first-line therapy for advanced adrenocortical carcinoma (ACC) is represented by EDP-M (etoposide, doxorubicin, cisplatin + mitotane). Progestins have shown cytotoxic activity both in vitro and in vivo on ACC; better EDP-M tolerability and efficacy have been hypnotized due to the association with progestins. (2) Methods: The feasibility and tolerability of EDP-M combined with oral megestrol acetate (EDP-MM) were tested in 24 patients (pts) affected by metastatic ACC with a low performance status (PS); the case group was compared with a 48 pts control group according to the propensity score. The secondary objectives were clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS). (3) Results: Thirteen pts (54.2%) in the EDP-MM population experienced progestin-related toxicities; in particular, five pts experienced vaginal bleeding (20.8%); four pts experienced weight gain (16.7%); and thromboembolic events, worsening of hypertension, skin rashes, and hyperglycemia were registered in one patient each (4.2%). This led to the discontinuation of megestrol acetate in four pts (16.7%). EDP-M-related toxicities were similar in both groups. No differences in PFS and OS curves were observed; the CBR was 75.0% and 60.4%, respectively. (4) Conclusions: The association of EDP-M + megestrol acetate in ACC pts with a low PS is feasible and well tolerated; its efficacy appeared to be non-inferior to EDP-M administered to pts with a good PS.

Is weight gain preventable in women with early breast cancer undergoing chemotherapy? A real-world study on dietary pattern, physical activity, and body weight before and after chemotherapy.

PURPOSE: We aimed to investigate the role of a lifestyle intervention and clinical and therapeutic factors for preventing weight gain in early breast cancer (BC) patients from one week before to 12 months after chemotherapy. METHODS: Dietary assessments were conducted by a trained dietician using a food-frequency questionnaire at each clinical assessment. Total energy, macronutrients intakes, and physical activity were estimated and the Mediterranean Diet Score (MDS) for adherence to Mediterranean diet was calculated. At each follow-up visit, patients were provided with dietary advices according to Mediterranean and Italian guidelines by a registered dietician, after evaluation of their food records. The associations of clinical characteristics, dietary pattern, and physical activity with weight gain were evaluated by multiple logistic regression, with weight gain ≥5% from baseline value as a dichotomous dependent variable. RESULTS: 169 early BC patients who met all follow-up visits and provided complete data were included in the analysis. From baseline to last assessment, weight loss (≥5% decrease from baseline value), stable weight, and weight gain were observed in 23.1%, 58%, and 18.9% women, respectively. Overall, a 0.68 kg mean decrease in women's weight (-1.1% from baseline) was observed. The risk of gaining weight increased for having normal weight/underweight at baseline, receiving hormone therapy, MDS worsening, and physical activity decreasing from baseline to last assessment. CONCLUSION: Providing simple suggestions on Mediterranean diet principles was effective for preventing weight gain in normal weight women and favoring weight loss in overweight and obese women.

Muscle quality and not quantity as a predictor of survival in head and neck squamous cell carcinoma.

BACKGROUND: Sarcopenia is frequent in head and neck squamous cell carcinoma (HNSCC), as a consequence of malnutrition related to risk factors or tumoral mass. Treatment is associated with toxicities that lead to reduced calories intake and muscle mass wasting. Sarcopenia has been negatively associated with tumor control and survival outcomes. PURPOSE: Our aim is to evaluate the prognostic impact of sarcopenia on overall survival (OS) and progression free survival (PFS) in HNSCC patients undergoing chemoradiation therapy within a prospective clinical trial of chemoradiation vs induction chemotherapy followed by radiation and cetuximab (INTERCEPTOR). MATERIALS AND METHODS: On baseline CT or MRI, we investigated the association between OS and PFS with radiological markers of sarcopenia, measured at the third cervical vertebra level. We studied paravertebral skeletal muscles area (cm2), muscle density (HU), muscle index (cm2/m2), and intermuscular adipose tissue (IMAT) area (cm2). RESULTS: Imaging of 128 patients was evaluable. We found out that higher body mass index (BMI) was associated with better OS (p = 0.02), and PFS (p = 0.04). Skeletal muscle area (p = 0.02), and IMAT (p = 0.02) were negatively associated with PFS. IMAT was positively correlated with muscle area (Correlation coefficient 0.6, CI95% 0.47-0.7), and negatively associated with muscle density (Correlation coefficient -0.37, CI95% -0.53 - -0.18). CONCLUSIONS: IMAT can be used as predictor of PFS in HNC patients undergoing chemoradiation therapy. The amount of intermuscular fat deposits induces alterations of muscle quality, without alterations of muscle quantity, influencing patients' prognosis.

Oncological results and cancer control definition in focal therapy for Prostate Cancer: a systematic review.

INTRODUCTION: Focal therapy (FT) is a promising alternative to whole-gland treatments for Localized Prostate Cancer. Ten different FT modalities have been described in literature. However, FT is not yet recommended by the International Guidelines, due to the lack of robust data on Oncological Outcomes. The objective of our Narrative Review is to evaluate the oncological profile of the available FT modalities and to offer a comprehensive overview of the definitions of Cancer Control for FT. MATERIAL AND METHODS: Literature search was performed on 21st February 2023 using PubMed, EMBASE, and Scopus, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). Articles reporting whole gland-treatments were excluded. All articles reporting oncological outcomes were included. RESULTS: One-hundred-twenty-four studies, reporting data on more than 8000 patients treated with FT, were included. Overall, 40 papers were on High Intensity Focal Ultrasound (HIFU), 24 on Focal Cryotherapy, 13 on Irreversible Electroporation (IRE), 11 on Focal brachytherapy, 10 on Focal Laser Ablation (FLA), 8 on Photo-Dynamic Therapy (PDT), 3 on Microwave ablation, 3 on Robotic Partial Prostatectomy, 2 on bipolar Radio Frequency Ablation (bRFA), 1 on Prostatic Artery Embolization (PAE) and 9 comparative papers. Overall, the Biochemical Recurrence (BCR) rate ranged from 0% (Focal Brachytherapy) to 67.5% (HIFU); the Salvage treatment rate ranged from 1% (IRE) to 54% (HIFU) considering re-treatment with FT and from 0% (Focal Brachytherapy) to 66.7% considering standard Radical Treatments. There is no univocal definition of Cancer Control, however the "Phoenix criteria" for BCR were the most commonly used. CONCLUSIONS: FT is a promising alternative treatment for localized prostate cancer in terms of Oncological Outcomes, however there is a wide heterogeneity in the definition of cancer control, the reporting of oncological outcomes and a lack of high-quality clinical trials. Solid comparative studies with standard treatments and an unambiguous consensus on how to describe Cancer Control in the field of Focal Therapy are needed.

Functional outcomes and safety of focal therapy for prostate cancer: a systematic review on results and patient-reported outcome measures (PROMs).

INTRODUCTION: Focal therapy (FT) is a promising alternative with curative intent for Low- to Intermediate-risk localized Prostate Cancer (PCa), claiming better functional outcomes and safety profile than standard whole-gland treatments. Ten different FT modalities have been described in the literature. The objective of our narrative review is to evaluate the safety profile and functional outcomes of these different modalities and the current most used tools of assessment for those outcomes. MATERIAL AND METHODS: Literature search was performed on 21st February 2023 using PubMed, EMBASE, and Scopus, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). Articles reporting whole-gland treatments were excluded. All articles reporting functional outcomes were included. RESULTS: One-hundred-seven studies, reporting data on 6933 patients, were included (26 on High Intensity Focal Ultrasound, 22 on Focal Cryotherapy, 14 on Irreversible Electroporation, 11 on Focal brachytherapy, 10 on Focal Laser Ablation, 8 on Photodynamic Therapy, 3 on Microwave ablation, 3 on Robotic Partial Prostatectomy, 2 on bipolar Radio Frequency Ablation, 1 on Prostatic Artery Embolization, and 7 studies comparing different FTs). Post-operative pad-free rate ranged between 92.3-100%. Greater heterogeneity exists considering the Change in Erectile Function, with Changing in Erectile function- rates ranging between 0-94.4% (Cryotherapy). The most used Patient-Reported Outcome Measures (PROMs) were the International Prostate Symptom Score and the International Index of Erectile Function for incontinence/urinary function and potency, respectively. The most common reported complications were hematuria, infections, and urethral strictures, with rates widely ranging among different treatments. The Clavien-Dindo Classification was the most used (40/88 papers) to describe adverse events. CONCLUSION: FT is a promising treatment for localized PCa, achieving excellent results in terms of safety and functional outcomes. There is a wide heterogeneity in the definition of PROMS and time of collection between studies. High quality comparative studies with standard treatments are needed to reinforce these findings.

Anticoagulation in acute ischemic stroke patients with mechanical heart valves: To bridge or not with heparin. The ESTREM study.

INTRODUCTION: The best therapeutic strategy for patients with mechanical heart valves (MHVs) having acute ischemic stroke during treatment with vitamin K antagonists (VKAs) remain unclear. Being so, we compared the outcomes for: (i) full dose heparin along with VKA (bridging therapy group) and (ii) restarting VKA without heparin (nonbridging group). PATIENTS AND METHODS: For this multicenter observational cohort study, data on consecutive acute ischemic stroke patients with MHV was retrospectively collected from prospective registries. Propensity score matching (PSM) was adopted to adjust for any treatment allocation confounders. The primary outcome was the composite of stroke, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding at 90 days. RESULTS: Overall, 255 out of 603 patients (41.3%) received bridging therapy: 36 (14.1%) had combined outcome, compared with 28 (8.0%) in the nonbridging group (adjusted OR 1.83; 95% CI 1.05-3.18; p = 0.03). Within the bridging group, 13 patients (5.1%) compared to 12 (3.4%) in the nonbridging group had an ischemic outcome (adjusted OR 1.71; 95% CI 0.84-3.47; p = 0.2); major bleedings were recorded in 23 (9.0%) in the bridging group and 16 (4.6%) in the nonbridging group (adjusted OR 1.88; 95% CI 0.95-3.73; p = 0.07). After PSM, 36 (14.2%) of the 254 bridging patients had combined outcome, compared with 23 (9.1%) of 254 patients in the nonbridging group (OR 1.66; 95% CI 0.95-2.85; p = 0.07). CONCLUSION: Acute ischemic stroke patients with MHV undergoing bridging therapy had a marginally higher risk of ischemic or hemorrhagic events, compared to nonbridging patients.

How Useful Is the SSN-Nipple Distance? An Analytical Questionnaire Survey on Anthropometric Measurements for the Aesthetically Ideal Positioning of the Nipple-Areolar Complex.

Several studies have attempted to identify the optimal anthropometric measurement for the aesthetically ideal positioning of the nipple-areolar complex. However, no standardised solutions and measurements for planning surgical procedures have been reached. The aim of this study is to identify the optimal anthropometric measurement between the suprasternal notch (SSN)-nipple distance and mid-clavicle (MC)-nipple distance for the aesthetic position of the nipple-areola complex (NAC) on the breast. A detailed online survey was sent to 300 board-certified plastic surgeons and residents of plastic surgery departments of hospitals in German, Austrian, and Swiss. A similar survey was also provided to 100 patients who had planned or had already undergone breast surgery. All participants were asked to rank the attractiveness of a series of women's breasts in images with different NAC position measurements. The images showed breasts from two different measurements and distances: all the breasts had equal dimensions and proportions and the same areola size. Complete datasets were obtained from 203 of the 300 board-certified plastic surgeons and residents of plastic surgery departments in German-speaking countries (recall 68%) and from 100 patients. The majority of doctors and patients find a symmetrical breast with a mirrored position of the nipple-areola complex more attractive than a non-symmetrical breast. In cases with minor measurement differences, such as 0.5 cm (SSN vs. MC), there is no relevant difference in the breast symmetry. However, at larger distances, the MC-to-nipple distance is superior for achieving aesthetically appealing symmetry compared with the SSN-to-nipple distance. Using the MC-to-nipple distance seems to be superior for correct nipple positioning than the SSN-to-nipple distance and is a valuable preoperative measurement option for breast symmetry with correct nipple height. Further studies on this topic involving a more general population should be conducted to confirm the improvements in perception with the preoperative measurements using the anatomical landmarks.

Clinical presentation and outcome of patients with enteric-type adenocarcinoma of the lung: A pooled analysis of published cases.

Enteric-type adenocarcinoma of the lung (lung-ETAC, former pulmonary enteric adenocarcinoma, PEAC) is a rare subtype of non-small cell lung cancer (NSCLC), which shares morphological and immunohistochemical features with lung and colorectal adenocarcinoma. Few data are available on patient prognosis, possible prognostic factors and systemic approach to metastatic disease. We performed a pooled analysis and a systematic review of published lung-ETAC, along with an additional case description. Thirty-one eligible publications were identified, providing data from 126 patients. In the 127 patients overall analyzed, median overall survival (OS) was 56.0 (range 36.7-75.3) months in early-stage patients and 14.0 (range 4.5-23.5) months in those with advanced/metastatic disease. Median disease-free survival (DFS) after radical surgery was 24 (range 22.6-35.1) months. Smoking status (HR 4.304, 95% CI: 1.261-14.693, p = 0.020) and node involvement (HR 1.853, 95% CI: 1.179-2.911, p = 0.007) were the negative independent prognostic factors at multivariate analysis. As regards systemic therapies for advanced cases, no firm conclusions were drawn about the efficacy of lung cancer-oriented chemotherapy regimens as opposed to colon cancer-oriented ones. Molecular analysis of lung-ETAC revealed a relatively high mutational rate, with alterations in several druggable molecular pathways, KRAS and NRAS (31%) were the most frequently mutated oncogenes, followed by ROS1 (15%), RET (13%), BRAF (11%), EGFR (8%) and ALK (6%). Moreover, 3 (15%) out of 20 cases showed DNA mismatch repair deficiency (dMMR). In conclusion, advanced lung-ETAC patients appeared to have a better prognosis compared to other subtypes of NSCLC. Moreover, the mutational rate and microsatellite instability found in lung-ETACs suggest that a significant proportion of these patients could benefit from target therapies and immunotherapy.

Androgen serum levels in male patients with adrenocortical carcinoma given mitotane therapy: A single center retrospective longitudinal study.

Objective: Hypogonadism is common in male patients with adrenocortical carcinoma (ACC) who are under treatment with mitotane, but the phenomenon is underestimated, and its prevalence has been poorly studied. This single-center retrospective longitudinal study was undertaken to assess the frequency of testosterone deficiency before and after mitotane therapy, the possible mechanism involved, and the relationship between hypogonadism with serum mitotane levels and prognosis. Research design and methods: Consecutive male ACC patients followed at the Medical Oncology of Spedali Civili Hospital in Brescia underwent hormonal assessment to detect testosterone deficiency at baseline and during mitotane therapy. Results: A total of 24 patients entered the study. Of these patients, 10 (41.7%) already had testosterone deficiency at baseline. During follow-up, total testosterone (TT) showed a biphasic evolution over time with an increase in the first 6 months followed by a subsequent progressive decrease until 36 months. Sex hormone binding globulin (SHBG) progressively increased, and calculated free testosterone (cFT) progressively decreased. Based on cFT evaluation, the proportion of hypogonadic patients progressively increased with a cumulative prevalence of 87.5% over the study course. A negative correlation was observed between serum mitotane levels >14 mg/L and TT and cFT. Conclusion: Testosterone deficiency is common in men with ACC prior to mitotane treatment. In addition, this therapy exposes these patients to further elevated risk of hypogonadism that should be promptly detected and counteracted, since it might have a negative impact on quality of life.

The association of cemiplimab plus sonidegib for synchronous cutaneous squamous cell carcinoma and basal cell carcinoma of the head and neck: Two case reports.

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequent cancers in humans, with cumulative ultraviolet radiation exposure, aging, and immunodepression as the main risk factors. In most cases, these malignancies arise in the head and neck area, and they can be treated with locoregional therapies. A minority of cases require systemic therapy. Currently, Sonic Hedgehog inhibitors (i.e., vismodegib and sonidegib) have been approved for advanced BCC, while the PD-1 checkpoint inhibitor cemiplimab has been approved as a first-line treatment for cSCC and as a second-line treatment for BCC. Nevertheless, there is a clinical need for an effective and safe systemic therapies for advanced synchronous (syn) BCC/cSCC not amenable to local treatments. International guidelines do not provide specific recommendations for patients affected by this condition, and no case reports on the full-dose association of these medications have been previously reported. Here, we present the cases of two elderly patients affected by synBCC/cSCC of the head and neck, who received combined therapy with cemiplimab and sonidegib at full dose and standard schedule, achieving remarkable clinical benefit and long-term responses, without major adverse events. The instance of a feasible treatment for patients with advanced synBCC/cSCC will become increasingly frequent with the advancement of life expectancy in the global population, and the synergistic activity of targeted therapies and immunotherapy-administered either in association or sequentially-deserves to be further explored.

Urinary Continence Recovery after Robotic Radical Prostatectomy without Anterior or Posterior Reconstruction: Experience from a Tertiary Referral Center.

BACKGROUND: The aim of our study is to evaluate the prevalence and predictive factors of short- (30 d) and mid-term continence in a contemporary cohort of patients treated with robotic-assisted laparoscopic prostatectomy (RALP) without any posterior or anterior reconstruction at our referral academic center. METHODS: Data from patients undergoing RALP between January 2017 and March 2021 were prospectively collected. RALP was performed by three highly experienced surgeons following the principles of the Montsouris technique, with a bladder-neck-sparing intent and maximal preservation of the membranous urethra (if oncologically safe) without any anterior/posterior reconstruction. (Self-assessed urinary incontinence (UI) was defined as the need of one or more pads per die (excluding the need for a safety pad/die. Univariable and multivariable logistic regression analysis was used to assess the independent predictors of early incontinence among routinely collected patient- and tumor-related variables). RESULTS: A total of 925 patients were included; of these, 353 underwent RALP (38.2%) without nerve-sparing intent. The median patient age and BMI were 68 years (IQR 63-72) and 26 (IQR 24.0-28.0), respectively. Overall, 159 patients (17.2%) reported early (30 d) incontinence. In multivariable analysis adjusting for patient- and tumor-related features, a non-nerve-sparing procedure (OR: 1.57 [95% CI: 1.03-2.59], p = 0.035) was independently associated with the risk of urinary incontinence in the short-term period, while the absence of cardiovascular diseases before surgery (OR: 0.46 [95% CI: 0.320.67], p ≤ 0.01) was a protective factor for this outcome. At a median follow-up of 17 months (IQR 10-24), 94.5% of patients reported to be continent. CONCLUSIONS: In experienced hands, most patients fully recover urinary continence after RALP at mid-term follow-up. On the contrary, the proportion of patients who reported early incontinence in our series was modest but not negligible. The implementation of surgical techniques advocating anterior and/or posterior fascial reconstruction might improve the early continence rate in candidates for RALP.

Treatment and outcome of metastatic parathyroid carcinoma: A systematic review and pooled analysis of published cases.

Background: Parathyroid carcinoma (PC) is an extremely rare malignant tumor with an incidence of about 6 new cases per 10 million inhabitants per year. While several papers have been published on treatments and outcomes of PC patients with loco-regional disease, little is known about the prognosis, treatment strategies, and prognostic factors of patients with distant metastasis. Materials and methods: We performed a systematic review and a pooled analysis of histopathologically confirmed PC cases published in literature using the following keywords: "metastasis-metastatic-secondary nodes" AND "parathyroid carcinoma". Original case reports and case series reporting metastatic parathyroid carcinoma were included. Data from 58 articles were extracted in a piloted form by five reviewers on a shared database. Results: Seventy-nine patients with metastatic PC were identified between 1898 and 2018. Ten (13%) patients had synchronous metastases, while metachronous metastases occurred in 43 (54%) patients. The remaining 26 patients developed metastatic disease concomitantly to local recurrence. Primary hyperparathyroidism guided the diagnosis of metastatic recurrence in 58 (73%) patients. Surgery was the main primary approach adopted, as it was performed in 43 (54%) patients. Twenty (25%) patients underwent systemic antineoplastic therapy, consisting of chemotherapy, immunotherapy, tyrosine kinase inhibitors, and hexestrol therapy. Bone resorption inhibitors had a limited efficacy in the long-term control of hypercalcemia. After a median follow-up of 37.5 months, 43 (55%) patients died, 22 (51%) due to the consequences of uncontrolled PHPT. The median overall survival was 36 months (range: 1-252). Surgery was associated with a better OS (HR 0.48, 95% CI 0.26-0.88), whereas bone metastases represented a negative prognostic factor (HR 2.7, 95% CI 1.4-5.2). Conclusion: Metastatic PC has a relatively poor prognosis. The main goals of treatment are to counteract tumor growth and control hypercalcemia. Surgery of metastases is the best approach to achieve rapid control of PHPT and longer survival. Target therapies and immunotherapy deserve to be extensively tested in metastatic PC and strategies to better control hypercalcemia should be implemented.