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Simple Summary: Completion lobectomy (CL) entails the resection of the remaining pulmonary lobe subsequent to wedge resection or segmentectomy. Indications for CL include reoperations for multiple or relapsed lung cancers and metastatic lung tumors, and the prognostic advantage of these procedures has been widely reported. However, ipsilateral surgical treatments, particularly within the same lobe, present challenges due to the development of intrapleural adhesions, rendering reoperation more difficult and time-consuming. VATS has emerged as the gold standard in the surgical treatment of early-stage NSCLC, offering superior postoperative outcomes when compared to thoracotomy. Its efficacy has been well established, even during complex procedures. However, its application in ipsilateral reoperations remains anecdotal, and to the best of our knowledge, no studies have analyzed the safety and efficacy of uniportal-VATS in this setting. This paper aims to evaluate the role of iniportal-VATS in CL long after wedge resection or anatomical segmentectomy in the same lobe. Background: Completion lobectomy (CL) following a prior resection in the same lobe may be complicated by severe pleural or hilar adhesions. The role of uniportal video-assisted thoracoscopic surgery (U-VATS) has never been evaluated in this setting. Methods: Data were collected from two Italian centers. Between 2015 and 2022, 122 patients (60 men and 62 women, median age 67.7 ± 8.913) underwent U-VATS CL at least 4 weeks after previous lung surgery. Results: Twenty-eight (22.9%) patients were affected by chronic obstructive pulmonary disease (COPD) and twenty-five (20.4%) were active smokers. Among the cohort, the initial surgery was performed using U-VATS in 103 (84.4%) patients, triportal-VATS in 8 (6.6%), and thoracotomy in 11 (9.0%). Anatomical segmentectomy was the initial surgery in 46 (37.7%) patients, while hilar lymphadenectomy was performed in 16 (13.1%) cases. CL was performed on 110 (90.2%) patients, segmentectomy on 10 (8.2%), and completion pneumonectomy on 2 (1.6%). Upon reoperation, moderate pleural adhesions were observed in 38 (31.1%) patients, with 2 (1.6%) exhibiting strong adhesions. Moderate hilar adhesions were found in 18 (14.8%) patients and strong adhesions in 11 (9.0%). The median operative time was 203.93 ± 74.4 min. In four (3.3%) patients, PA taping was performed. One patient experienced intraoperative bleeding that did not require conversion to thoracotomy. Conversion to thoracotomy was necessary in three (2.5%) patients. The median postoperative drainage stay and postoperative hospital stay were 5.67 ± 4.44 and 5.52 ± 2.66 days, respectively. Postoperative complications occurred in 34 (27.9%) patients. Thirty-day mortality was null. Histology was the only factor found to negatively influence intraoperative outcomes (p = 0.000). Factors identified as negatively impacting postoperative outcomes at univariate analyses were male sex (p = 0.003), age > 60 years (p = 0.003), COPD (p = 0.014), previous thoracotomy (p = 0.000), previous S2 segmentectomy (p = 0.001), previous S8 segmentectomy (p = 0.008), and interval between operations > 5 weeks (p= 0.005). In multivariate analysis, only COPD confirmed its role as an independent risk factor for postoperative complications (HR: 5.12, 95% CI (1.07–24.50), p = 0.04). Conclusions: U-VATS CL seems feasible and safe after wedge resection and anatomical segmentectomy. [ABSTRACT FROM AUTHOR]

Simple Summary: Since the introduction of effective systemic therapies (ESTs) (in the form of both targeted and immuno-based therapies) in the treatment of malignant melanoma, the prognosis of metastatic patients has dramatically changed. The role of metastasectomy in oligometastatic patients has rarely been addressed in this new pharmacological era. Even though lungs represent the most frequent site of melanoma metastases, only limited data are available on the role of surgery in isolated pulmonary metastases from malignant melanoma (PmMM). In this study, we describe the outcomes of patients who underwent metastasectomy of PmMM in the era of ESTs, and identified prognostic factors affecting survival in our multicentric experience. To the best of our knowledge, this is the first paper analyzing in detail the impact of metastasectomy of PmMM in the era of ESTs. In the last decade, the emergence of effective systemic therapies (ESTs) in the form of both targeted and immuno-based therapies has revolutionized the treatment of patients with advanced stage III and stage IV melanoma. Even though lungs represent the most frequent site of melanoma metastases, only limited data are available on the role of surgery in isolated pulmonary metastases from malignant melanoma (PmMM) in the era of ESTs. The aim of this study is to describe the outcomes of patients who underwent metastasectomy of PmMM in the era of ESTs, in order to identify prognostic factors affecting survival and to provide a framework for more informed patient selection of treatmeant with lung surgery in the future. Clinical data of 183 patients who underwent metastasectomy of PmMM between June 2008 and June 2021 were collected among four Italian Thoracic Centers. The main clinical, surgical and oncological variables reviewed were: sex, comorbidities, previous oncological history, melanoma histotypes and primary site, date of primary cancer surgical treatment, melanoma growth phase, Breslow thickness, mutation pattern disease, stage at diagnosis, metastatic sites, DFI (Disease Free Interval), characteristics of lung metastases (number, side, dimension, type of resection), adjuvant therapy after lung metastasectomy, site of recurrence, disease-free survival (DFS) and cancer-specific survival (CSS; defined as the time interval between the first melanoma resection or lung metastasectomy and death from cancer). All patients underwent surgical resection of the primary melanoma before lung metastasectomy. Twenty-six (14.2%) patients already had a synchronous lung metastasis at the time of primary melanoma diagnosis. A wedge resection was performed in 95.6% of cases to radically remove the pulmonary localizations, while an anatomical resection was necessary in the remaining cases. The incidence of major post-operative complications was null, while only 21 patients (11.5%) developed minor complications (mainly air leakage followed by atrial fibrillation). The mean in-hospital stay was 4.46 ± 2.8 days. Thirty- and sixty-day mortality were null. After lung surgery, 89.6% of the population underwent adjuvant treatments (47.0% immunotherapy, 42.6% targeted therapy). During a mean FUP of 107.2 ± 82.3 months, 69 (37.7%) patients died from melanoma disease, 11 (6.0%) from other causes. Seventy-three patients (39.9%) developed a recurrence of disease. Twenty-four (13.1%) patients developed extrapulmonary metastases after pulmonary metastasectomy. The CSS from melanoma resection was: 85% at 5 years, 71% at 10 years, 54% at 15 years, 42% at 20 years and 2% at 25 years. The 5- and 10-year CSS from lung metastasectomy were 71% and 26%, respectively. Prognostic factors negatively affecting CSS from lung metastasectomy at multivariable analysis were: melanoma vertical growth (p = 0.018), previous metastatic sites other than lung (p < 0.001) and DFI < 24 months (p = 0.007). Our results support the evidence that surgical indication confirms its important role in stage IV melanoma with resectable pulmonary metastases, and selected patients can still benefit from pulmonary metastasectomy in terms of overall cancer specific survival. Furthermore, the novel systemic therapies may contribute to prolonged survival after systemic recurrence following pulmonary metastasectomy. Patients with long DFI, radial growth melanoma phase and no site of metastatization other than lung seem to be the best candidate cases for lung metastasectomy; however, to drive stronger conclusions, further studies evaluating the role of metastasectomy in patients with iPmMM are needed. [ABSTRACT FROM AUTHOR]

Simple Summary: This article regards the incidence of long COVID symptoms in a cohort of patients with cancer with or without previous treatment with early therapies anti-SARS-CoV-2 in an out-of-hospital setting. The enrolled patients were invited to take part in the survey by telephone at least 12 weeks after COVID-19 diagnosis in order to evaluate the incidence of long COVID symptoms. To date, no papers have focused on the oncological population managed at home with the early anti-SARS-CoV-2 therapies. The overlap between the symptoms related to the oncological disease/oncological treatment and the symptoms of long COVID is one of the main future challenges that oncologists will have to manage. The incidence of long COVID in a cohort of patients with cancer with or without previous treatment with early therapies anti-SARS-CoV-2 in an out-of-hospital setting have to be elucidated. We prospectively enrolled all patients treated for a solid tumor at the department of Medical Oncology of the Fondazione IRCCS Policlinico San Matteo with a positive SARS-CoV-2 antigen or polymerase chain reaction test from January to September 2022 (Omicron surge). Ninety-seven patients answered the survey questions by telephone at least 12 weeks after COVID-19 diagnosis in order to evaluate the incidence of long COVID symptoms. Only twelve patients (12.4%) reported long COVID. No significant difference between early therapies anti-SARS-CoV-2 31 and long COVID (p = 0.443) was seen. The female sex (p = 0.024) and diabetes mellitus (p = 0.014) are significantly associated with long COVID. No statistically significant difference between the two groups (Long COVID vs. No Long COVID) according to the time to nasal swab viral clearance (p = 0.078). The overlap between the symptoms related to the oncological disease/oncological treatment and the symptoms of long COVID is one of the main future challenges that oncologists will have to manage. [ABSTRACT FROM AUTHOR]

Simple Summary: Interventional oncology provides minimally invasive alternatives to many traditional medical and surgical treatments, offering a potential cure, control, or palliative care for many types of cancer patients. The aim of this article is to comprehensively review new indications for locoregional interventional oncology treatments and summarize the expert discussion and report from the "MIOLive Meets SIO" (Society of Interventional Oncology) session during the last Mediterranean Interventional Oncology Live congress held in Rome, Italy. Interventional oncology (IO) employs image-guided techniques to perform minimally invasive procedures, providing lower-risk alternatives to many traditional medical and surgical therapies for cancer patients. Since its advent, due to rapidly evolving research development, its role has expanded to encompass the diagnosis and treatment of diseases across multiple body systems. In detail, interventional oncology is expanding its role across a wide spectrum of disease sites, offering a potential cure, control, or palliative care for many types of cancer patients. Due to its widespread use, a comprehensive review of the new indications for locoregional procedures is mandatory. This article summarizes the expert discussion and report from the "MIOLive Meet SIO" (Society of Interventional Oncology) session during the last MIOLive 2022 (Mediterranean Interventional Oncology Live) congress held in Rome, Italy, integrating evidence-reported literature and experience-based perceptions. The aim of this paper is to provide an updated review of the new techniques and devices available for innovative indications not only to residents and fellows but also to colleagues approaching locoregional treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: The prevalence of second neoplasms among patients with hairy cell leukemia (HCL) treated with cladribine is not negligible. Immunosuppression, high rate of cure, and aging may have a role in the pathogenesis of second cancers after HCL. We aimed to compare the risk of cancer between patients with HCL treated with cladribine and the general population. Concern has emerged about the prevalence of second cancers among patients with hairy cell leukemia (HCL) treated with purine analogs. We investigated 513 patients with HCL treated with cladribine over the last 30 years at 18 Italian centers and calculated their standardized incidence ratios (SIRs). We identified 24 patients with a second cancer diagnosed at a median time from treatment with cladribine of 59.9 months (range: 9.2–169.7 months). All patients with solid neoplasms presented with a limited-stage disease, except four cases of locally advanced cancer; multiple myeloma patients had a smoldering disease, while lymphoma patients had stage Ie and stage IV diseases. Response to therapy was complete in 19 cases; 1 patient is still receiving treatment for a relapsing bladder disease, while 2 patients progressed during treatment and died. These two patients died from unrelated causes: one from infection and one due to surgery complications. The median OS from HCL was 98.5 months (range: 38.4–409.2 months), while the median OS from second cancer was 27.6 months (range: 1–117.8 months). The SIR was 0.86 (95% CI: 0.54–1.30) for males and 1.13 (95% CI: 0.36–2.73) for females: no statistically significant differences were highlighted. We were not able to demonstrate an excess of second cancer or a significant association with the specific studied neoplasm. [ABSTRACT FROM AUTHOR]

Simple Summary: In situ/microinvasive adenocarcinoma of the uterine cervix represents the majority of cervical glandular lesions and can be treated conservatively. In contrast to squamous lesions, approximately 15–20% of glandular disease may be HPV-negative and therefore associated with a worse prognosis. Furthermore, up to 4% of cases may show recurrence after three years of follow-up. Given the abovementioned risk, knowing the predictive factors of disease recurrence becomes crucial for post-treatment management. In the present study, HPV testing in follow-up was the best predictor for recurrences in women with in situ/microinvasive AC undergoing conservative treatment. So, its use in clinical practice is of pivotal importance. However, attention should be paid to non-high-risk HPV women in follow-up with non-usual-type histopathology, given that it seems to represent a sub-population at increased risk of recurrences. Objective: The present study aimed to assess long-term follow-up outcomes in women with in situ/microinvasive adenocarcinoma (AC) of the uterine cervix treated conservatively. Methods: Retrospective multi-institutional study including women with early glandular lesions and 5-year follow-up undergoing fertility-sparing treatment. Independent variables associated with recurrence were evaluated. Logistic regression analysis and Kaplan–Meier survival analysis with Logrank test were performed. Results: Of 269 women diagnosed with in situ/microinvasive AC, 127 participants underwent conservative treatment. During follow-up, recurrences were found in nine women (7.1%). The only factor associated with recurrence during follow-up was positive high-risk Human Papillomavirus (hr-HPV) testing (odds ratio 6.21, confidence interval 1.47–26.08, p = 0.012). HPV positivity in follow-up showed a recurrence rate of 21.7% against 3.8% in patients who were HPV-negative (p = 0.002, Logrank test). Among women with negative high-risk HPV tests in follow-up, recurrences occurred in 20.0% of non-usual-type histology vs. 2.1% of usual-type cases (p = 0.005). Conclusion: HPV testing in follow-up is of pivotal importance in women with early glandular lesions undergoing conservative treatment, given its recurrence predictive value. However, women who are high-risk HPV-negative in follow-up with non-usual-type histopathology may represent a sub-population at increased risk of recurrences. Further studies should confirm these findings. [ABSTRACT FROM AUTHOR]

Simple Summary: This study was conducted to compare two endoscopic procedures for managing malignant gastric outlet obstruction. The first and most commonly used procedure is enteral stenting, which is safe, easy, and widely available. The second procedure, endoscopic ultrasound-guided gastroenterostomy (EUS-GE), is more challenging, can result in severe adverse events, and requires specific skills. However, EUS-GE, which bypasses the tumor, could have some advantages in terms of the stent dysfunction rate. Our study found that stent dysfunction occurred more frequently after enteral stenting, while stent patency was longer after EUS-GE. However, the early clinical efficacy was comparable between the two procedures and was influenced by patients' performance status. This study suggests that the choice between these two techniques should be personalized based on several factors, including patients' prognosis and life expectancy, clinical success, and local expertise. Background: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) using lumen apposing metal stent has emerged as a minimally invasive treatment for the management of malignant gastric outlet obstruction (mGOO). We aimed to compare EUS-GE with enteral stenting (ES) for the treatment of mGOO. Methods: Patients who underwent EUS-GE or ES for mGOO between June 2017 and June 2023 at two Italian centers were retrospectively identified. The primary outcome was stent dysfunction. Secondary outcomes included technical success, clinical failure, safety, and hospital length of stay. A propensity score-matching analysis was performed using multiple covariates. Results: Overall, 198 patients were included (66 EUS-GE and 132 ES). The stent dysfunction rate was 3.1% and 16.9% following EUS-GE and ES, respectively (p = 0.004). Using propensity score-matching, 45 patients were allocated to each group. The technical success rate was 100% for both groups. Stent dysfunction was higher in the ES group compared with the EUS-GE group (20% versus 4.4%, respectively; p = 0.022) without differences in clinical efficacy (p = 0.266) and safety (p = 0.085). A significantly shorter hospital stay was associated with EUS-GE compared with ES (7.5 ± 4.9 days vs. 12.5 ± 13.0 days, respectively; p = 0.018). Kaplan–Meier analyses confirmed a higher stent dysfunction-free survival rate after EUS-GE compared with ES (log-rank test; p = 0.05). Conclusion: EUS-GE offers lower rates of stent dysfunction, longer stent patency, and shorter hospital stay compared with ES. [ABSTRACT FROM AUTHOR]

Simple Summary: Synchronous oligometastatic non-small cell lung cancer (NSCLC) represents an intermediate state of metastatic disease with a limited number of metastases. It has been suggested that adding local radical treatment (LRT) in this setting may improve the survival outcomes, but there are no validated tools to better select those patients who are most likely to benefit from LRT. The presence of cachexia and sarcopenia at diagnosis seems to be linked to poorer outcomes in local or advanced NSCLC, but it is not clear if these factors can be used to guide the treatment decisions in oligometastatic NSCLC and to preclude a possible radical treatment in patients with baseline cachexia or sarcopenia. For this reason, we evaluated the impact of cachexia and sarcopenia on survival outcomes and toxicities in a group of patients with synchronous oligometastatic NSCLC on an intention-to-treat basis. Considering the different definitions of sarcopenia used among different studies, we used the Psoas Muscle Index (PMI) as a surrogate of sarcopenia. Progression-free survival was longer for patients without cachexia and sarcopenia compared to those with cachexia and/or sarcopenia. Among patients with advanced NSCLC, there is a group of patients with synchronous oligometastatic disease (sOMD), defined as a limited number of metastases detected at the time of diagnosis. As cachexia and sarcopenia are linked to poor survival, incorporating this information could assist clinicians in determining whether a radical treatment should be administered. In a retrospective multicenter study, including all patients with adequately staged (FDG-PET, brain imaging) sOMD according to the EORTC definition, we aimed to assess the relationship between cachexia and/or sarcopenia and survival. Of the 439 patients that were identified between 2015 and 2021, 234 met the criteria for inclusion and were included. The median age of the cohort was 67, 52.6% were male, and the median number of metastasis was 1. Forty-six (19.7%) patients had cachexia, thirty-four (14.5%) had sarcopenia and twenty-one (9.0%) had both. With a median follow-up of 49.7 months, median PFS and OS were 8.6 and 17.3 months, respectively. Moreover, a trend toward longer PFS was found in patients without cachexia and sarcopenia compared to those with cachexia and/or sarcopenia. In multivariate analysis, cachexia and sarcopenia were not associated with an inferior survival, irrespective of receiving radical treatment. High CRP was associated with inferior survival and could be a prognostic factor, helping the decision of clinicians in selecting patients who may benefit from the addition of LRT. However, despite the homogeneous definition of oligometastatic disease and the adequate staging, our subgroups were small. Therefore, further studies are needed to better understand our hypothesis and generating findings. [ABSTRACT FROM AUTHOR]

Simple Summary: Third-line or further treatments are rarely given to patients with refractory mCRC. In this regard, two noteworthy innovative therapy options, with varying toxicity profiles and statistically significant improvements in overall survival (OS), progression-free survival (PFS), and disease control, are regorafenib (R) and trifluridine/tipiracil (T). This study is a subset analysis of a larger retrospective study that we have already published, with the aim of evaluating patient outcomes when R and T were administered in that order. The purpose of this analysis was to evaluate the relationship between survival outcomes and the first drug treatment duration (<3 months, 3 to <6 months, and ≥6 months) in patients who had received the regorafenib-to-trifluridine/tipiracil sequence or vice versa. Our substudy found that administering R three to six months prior to T can prolong both OS and PFS in comparison to the opposite sequence. Background: Patients with refractory metastatic colorectal cancer (mCRC) rarely receive third-line or further treatment. In this context, regorafenib (R) and trifluridine/tipiracil (T) are two important novel therapeutic choices with statistically significant increases in overall survival (OS), progression-free survival (PFS), and disease control, with different toxicity profiles. This study is a subgroup analysis of our larger retrospective study, already published, whose objective was to assess the outcomes of patients when R and T were given sequentially. Patients and Methods: The study involved thirteen Italian cancer centers on a 10-year retrospective observation (2012–2022). In this subgroup analysis, we focused our attention on the correlation between the first drug treatment duration (<3 months, 3 to <6 months and ≥6 months) and survival outcomes in patients who had received the sequence regorafenib-to-trifluridine/tipiracil, or vice versa. Results: The initial study included 866 patients with mCRC who received sequential T/R, or R/T, or T or R alone. This analysis is focused on evaluating the impact of the duration of the first treatment in the sequence on clinical outcomes (OS, PFS) and includes 146 and 116 patients of the T/R and R/T sequences, respectively. Based on the duration of the first drug treatment, subgroups for the T/R sequence included 27 patients (18.4%) who received T for <3 months, 86 (58.9%) treated for 3 to <6 months, and 33 (22.6%) treated for ≥6 months; in the reverse sequence (R as the first drug), subgroups included 18 patients (15.5%) who received their first treatment for <3 months, 62 (53.4%) treated for 3 to <6 months, and 35 (31.0%) treated for ≥6 months. In patients who received their first drug treatment for a period of 3 to <6 months, the R/T sequence had a significantly longer median OS (13.7 vs. 10.8 months, p = 0.0069) and a longer median PFS (10.8 vs. 8.5 months, p = 0.0003) than the T/R group. There were no statistically significant differences between groups with first drug treatment durations of <3 months and ≥6 months. Conclusions: Our analysis seems to suggest that the administration of R for a period of 3 to <6 months before that of T can prolong both OS and PFS, as compared to the opposite sequence. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment with cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), has demonstrated significantly improved progression-free survival in patients with hormone receptor-positive, HER2-negative, advanced breast cancer, when used in combination with endocrine therapies. However, limited data exists on its cutaneous adverse events (AE). The aim of our retrospective study was to investigate the prevalence, types and management of cutaneous AE during CDK4/6i. 79 adult advanced breast cancer patients affected by 125 skin adverse events during treatment with CDK4/6i were recruited at eleven centers. The most frequent cutaneous reactions were pruritus (49/79 patients), alopecia (25/79), and ec-zematous lesions (24/79). We showed that skin reactions are usually mild in severity, and prompt management may limit the negative impact on patients, facilitating beneficial continuation of oncologic treatment. Background: The introduction of cyclin-dependent kinase inhibitors (CDK4/6i) was a great advance in therapeutics for patients with estrogen receptor+/human epidermal growth factor receptor (HER2) locally advanced and metastatic breast cancer. Despite the increasing use of these agents, their adverse drug-related events have not yet been fully characterized. We describe the spectrum of cutaneous adverse reactions occurring in advanced breast cancer patients treated with cyclin-dependent kinase inhibitors, analyzing types, severity, time to onset, and possible treatment outcomes. Methods: We performed a multicentric retrospective study including patients with advanced breast cancer who developed cutaneous lesions during treatment with CDK4/6i in the period from June 2020 to June 2021. Patients > 18 years were recruited at eleven onco-dermatology units located in Albania (1), Argentina (1), France (1), Greece (3), Italy (3), and Spain (2). We evaluated patients' epidemiological and clinical characteristics, types of cutaneous adverse events, their time to onset, and treatment outcomes. The severity of the skin reactions was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 score. Results: Seventy-nine patients (median age: 62.3 years; range 39–83 years) were included in the study, and, collectively, we recorded a total of 165 cutaneous adverse events during follow-up visits. The most frequent cutaneous reactions were pruritus (49/79 patients), alopecia (25/79), and eczematous lesions (24/79). Cutaneous toxicities were usually mild in severity (>65%) and occurred after a median of 6.5 months. Only four patients (5%) required treatment discontinuation due to the severity of the skin lesions. The majority of the skin reactions were managed with topical treatments. Conclusions: To the best of our knowledge, we present the largest case series of cutaneous adverse events developing in advanced breast cancer patients treated with CDK4/6i. We showed that cutaneous toxicities are usually mild in severity, and manageable with standard supportive care; however, in selected cases, they can lead to treatment discontinuation with possible implications for patients' clinical outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Actinic keratosis (AK) is a premalignant skin lesion caused by chronic sun damage, which usually arises in older people on chronically sun-exposed areas of the body, such as the face, scalp, ears, neck, back of the forearms and hands. Actinic keratosis rarely occurs as a single lesion; most often it can involve multiple lesions in a field of cancerization. Since the AKs may progress to invasive squamous cell carcinoma, treatment of any AK regardless of clinical severity is strongly recommended. The goals of AK therapy are to eradicate clinical and subclinical lesions, prevent the progression into invasive squamous cell carcinoma, provide a good cosmetic outcome and reduce the risk of relapses. Multiple treatment options are available for this condition; however, no gold standard therapy has been established. A novel formulation of 4% 5-Fluorouracil with once daily application proved to be a highly effective and safe treatment for multiple actinic keratoses. Background: Actinic keratosis (AK) is one of the most common skin diseases, with a low risk of progression into invasive squamous cell carcinoma. We aim to assess efficacy and safety of a novel formulation of 5-Fluorouracil (5-FU) 4% with once daily application for the treatment of multiple AKs. Methods: A pilot study was performed on 30 patients with a clinical and dermoscopic diagnosis of multiple AKs, enrolled between September 2021 and May 2022 at the Dermatology Departments of two Italian hospitals. Patients were treated with 5-FU 4% cream once daily for 30 consecutive days. The Actinic Keratosis Area and Severity Index (AKASI) was calculated before starting therapy, and at each follow-up, to assess objective clinical response. Results: The cohort analyzed included 14 (47%) males and 16 (53%) females (mean age: 71 ± 12 years). A significant decrease in AKASI score at both 6 and 12 weeks (p < 0.0001) was observed. Only three patients (10%) discontinued therapy, and 13 patients (43%) did not report any adverse reactions; no unexpected adverse events were observed. Conclusions: In the setting of topical chemotherapy and immunotherapy, the new formulation of 5-FU 4% proved to be a highly effective treatment for AKs and field cancerization. [ABSTRACT FROM AUTHOR]

Simple Summary: This Phase 2 double-blind placebo-controlled clinical trial was conducted in 116 stage III/IV head-neck squamous cell carcinoma patients to evaluate the role of SAMITAL in reducing the incidence of severe mucositis induced by concurrent chemo-radiotherapy. SAMITAL does not significantly reduce the incidence of severe mucositis; However, the lower rate of mucositis, together with a significantly better quality of life, suggested that a clinical benefit existed, and further research is needed to validate these findings. This trial is registered with the EU Clinical Trials Register database, number 2012-002046-20, and with ClinicalTrials.gov, NCT01941992. Background: In patients affected by head and neck squamous cell carcinoma, the onset of severe oral mucositis is a decisive factor in completing concurrent chemo-radiotherapy, and few interventions have demonstrated a modest benefit. The primary aim of this clinical study was to evaluate the role of SAMITAL in reducing the incidence of severe mucositis induced by concurrent chemo-radiotherapy; the secondary aims were the tolerability and patient-reported quality of life measures. Methods: Patients were randomized to receive SAMITAL granules for oral suspension of 20 mL, four-time daily or matching placebo in a 1:1 fashion using a stratified-block randomization scheme by disease site and type of chemotherapy. The SAMITAL/placebo was dispensed at the baseline visit and at each weekly visit following radiotherapy initiation. Patients were subjected to weekly endoscopic evaluations to assess the presence of mucositis. In addition, patient-reported outcomes were measured. Results: Among the 116 patients treated with a median total dose of 66 Gy, 59 were randomized to SAMITAL and 57 to placebo. Overall, the incidence of severe mucositis was 51.7%, with 45.8% in the SAMITAL and 57.9% in the placebo arm (OR = 0.6; 95% CI: 0.3–1.3). After chemo-radiotherapy, patients randomized to SAMITAL reported significantly lower xerostomia, coughing and swallowing scores and a better quality of life. Conclusion: SAMITAL did not significantly reduce the incidence of severe mucositis in all studied populations. However, the lower rate of mucositis, together with a significantly better quality of life, suggested that a clinical benefit existed. This trial is registered with the EU Clinical Trials Register database, number 2012-002046-20, and with ClinicalTrials.gov, NCT01941992. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 are an even greater challenge for hematologists. To better clarify their outcome, we describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. Overall, 343 (76.2%) patients received treatment for HM, and an overall response rate was observed in 140 (40.8%) patients after the first line of treatment. Thirty-day mortality was significantly higher in patients not receiving HM treatment (42.1%) than in those receiving treatment (27.4%, p = 0.004). Statistical analysis showed that, together with age, severe/critical COVID-19, ≥2 comorbidities, lack of HM treatment was an independent risk factors for mortality. These observations suggest the importance of HM treatment in these patients; therefore, it should be delivered as soon as possible for patients requiring immediate therapy. Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines. Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients after the first line of treatment. After a median follow-up of 35 days, overall mortality was 177/450 (39.3%); 30-day mortality was significantly higher in patients not receiving HM treatment (42.1%) than in those receiving treatment (27.4%, p = 0.004), either before and/or after COVID-19, or compared to patients receiving HM treatment at least after COVID-19 (15.2%, p < 0.001). Age, severe/critical COVID-19, ≥2 comorbidities, and lack of HM treatment were independent risk factors for mortality, whereas a lymphocyte count >500/mcl at COVID-19 onset was protective. Conclusions: HM treatment should be delivered as soon as possible for patients with simultaneous diagnosis of COVID-19 and HM requiring immediate therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Data regarding the effect of pre-existent sarcopenia on the oncological outcome of advanced thyroid cancer patients treated with tyrosine kinase (TKI) are still lacking. The aim of the study was to investigate the prevalence of pre-treatment sarcopenia in Caucasian patients affected by advanced thyroid carcinoma and the impact of this condition on the response to TKIs treatment. Pre-treatment sarcopenia was found in 20.7% of patients, with an increase of up to 38.5% after 12 months of TKI therapy. Pre-treatment sarcopenia significantly affected treatment outcome, emerging as the parameter that has the greatest impact on Progression Free Survival. Sarcopenia might be used as a prognostic factor of TKI treatment outcome and the prevention of this condition, ideally before starting anticancer treatment, could be the strategy to obtain a better efficacy of therapy. (1) Background: Sarcopenia is associated with poor survival and treatment outcomes in several human cancers. The aim of the study was to investigate the prevalence of sarcopenia in a cohort of 58 Caucasian patients with advanced thyroid cancer before and during TKI treatment. The impact of this condition on the outcome of patients was also evaluated. (2) Methods: Sarcopenia was evaluated using the Skeletal Muscle Index (SMI). (3) Results: Pre-treatment sarcopenia was found in 20.7% of patients and this condition significantly affected treatment outcome, emerging as the parameter that has the greatest impact on Progression Free Survival (PFS) (HR 4.29; 95% CI, 1.21–15.11, p = 0.02). A significant reduction in SMI values was observed 3 (p = 0.002) and 12 months (p < 0.0001) after TKI treatment. At a 12-month follow-up, sarcopenia prevalence increased up to 38.5%. Here, 12-month sarcopenia was predicted by a lower SMI (p = 0.029), BMI (p = 0.02) and weight (p = 0.04) and by the presence of bone metastases (p = 0.02). (4) Conclusions: This is the first study that evaluated sarcopenia prevalence and its change over time in Caucasian patients with advanced thyroid cancer under TKI therapy. Sarcopenia seems to be a prognostic factor of TKI treatment outcome, suggesting the importance of the assessment of the nutritional status and body composition in advanced thyroid cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Disability is a temporary phenomenon for every child, adolescent, and young adult with hematological malignancies during the intensive phases of cancer treatment, but it can become a long-lasting condition for many. Disability is an umbrella term for impairments, activity limitations and participation restrictions, denoting the negative aspects of the interaction between an individual and that individual's contextual, environmental, and personal factors. Adapted precision-based training programs during cancer treatment are an emerging therapeutic option in pediatric oncology and evaluating the impact of tailored exercise on individuals' performance is mandatory for adapting exercise/sports activities. Our research showed that a new intermittent and recovery test, the Yo-Yo AD, provided valid information on an individual's capacity to perform repeated intense exercise and to follow up on the impact of precision-based exercise intervention in childhood hematological malignancies. During cancer treatments in childhood hematological malignancies, reduced exercise tolerance is one of the main hardships. Precision-based training programs help children, adolescents, and young adults and their families to resume regular physical activity, exercise, and sports once they return to their communities after the intensive phases spent in hospital. This study was aimed at verifying whether an intermittent recovery test, the Yo-Yo AD, could provide a simple and valid way to evaluate an individual's capacity to perform repeated intense exercise and to follow up on the impact of tailored exercise in children, adolescents, and young adults with hematological malignancies. The Yo-Yo AD involved the repetition of several shuttles to muscle exhaustion, at pre-established speeds (walking and slow running). The heart rate (HR) and oxygen saturation (SaO2) were monitored during the test. The total distance and the walking/running ability, measured as the slope of the HR vs. distance correlation, were investigated before (T0) and after 11 weeks (T1) of precision exercise intervention. The Yo-Yo AD was also performed by healthy children (CTRL). Ninety-seven patients (10.58 ± 4.5 years, 46% female) were enrolled. The Yo-Yo AD showed the positive impact of the exercise intervention by increasing the distance covered by the individuals (T0 = 946.6 ± 438.2 vs. T1 = 1352.3 ± 600.6 m, p < 0.001) with a more efficient walking/running ability (T0 = 2.17 ± 0.84 vs. T1 = 1.73 ± 0.89 slope, p < 0.0164). CTRLs performed better (1754.0 ± 444.0 m, p = 0.010). They were equally skillful (1.71 ± 0.27 slope) when compared to the patients after they received the precision-based intervention. No adverse events occurred during the Yo-Yo AD and it proved to be an accurate way of correctly depicting the changes in performance in childhood hematological malignancies. [ABSTRACT FROM AUTHOR]

Simple Summary: During first-line treatment of metastatic colorectal cancer, drug holidays (DHs) are usually adopted to limit toxicity. Literature lacks a formal demonstration that first-line continuous treatment, or maintenance, provides longer overall survival compared to DHs. We retrospectively studied the overall survival impact of DHs, demonstrating that a treatment break after initial induction chemotherapy may be considered in carefully clinically selected patients with metastatic colorectal cancer. Our study should reassure medical oncologists dedicated to colorectal cancer on the use of DHs. Different de-escalation strategies have been proposed to limit the risk of cumulative toxicity and guarantee quality of life during the treatment trajectory of patients with metastatic colorectal cancer (mCRC). Programmed treatment interruptions, defined as drug holidays (DHs), have been implemented in clinical practice. We evaluated the association between DHs and overall survival (OS). This was a retrospective study, conducted at the University Hospital of Udine and the IRCCS CRO of Aviano. We retrieved records of 608 consecutive patients treated for mCRC from 1 January 2005 to 15 March 2017 and evaluated the impact of different de-escalation strategies (maintenance, DHs, or both) on OS through uni- and multivariate Cox regression analyses. We also looked at attrition rates across treatment lines according to the chosen strategy. In our study, 19.24% of patients received maintenance therapy, 16.12% DHs, and 9.87% both, while 32.07% continued full-intensity first-line treatment up to progression or death. In uni- and multivariate analyses first-line continuous treatment and early discontinuation (treatment for less than 3 months) were associated to worse OS compared to non-continuous strategies (HR, 1.68; 95% CI, 1.22–2.32; p = 0.002 and HR,4.89; 95% CI, 3.33–7.19; p < 0.001, respectively). Attrition rates were 22.8%, 20.61%, and 19.64% for maintenance, DHs, or both, respectively. For continuous therapy and for treatment of less than 3 months it was 21.57% and 49%. De-escalation strategies are safe and effective options. DHs after initial induction chemotherapy may be considered in clinically selected patients with metastatic colorectal cancer. [ABSTRACT FROM AUTHOR]

Background obesity and sedentary lifestyle have been shown to negatively affect survival in breast cancer (BC). The purpose of this study was to test the efficacy of a lifestyle intervention on body mass index (BMI) and physical activity (PA) levels among BC survivors in Modena, Italy, in order to show an outcome improvement in obese and overweight patients. Methods: This study is a single-arm experimental design, conducted between November 2009 and May 2016 on 430 women affected by BC. Weight, BMI, and PA were assessed at baseline, at 12 months, and at the end of the study. Survival curves were estimated among normal, overweight, and obese patients. Results: Mean BMI decreased from baseline to the end of the study was equal to 2.9% (p = 0.065) in overweight patients and 3.3% in obese patients (p = 0.048). Mean PA increase from baseline to the end of the study was equal to 125% (p < 0.001) in normal patients, 200% (p < 0.001) in overweight patients and 100% (p < 0.001) in obese patients. After 70 months of follow-up, the 5-year overall survival (OS) rate was 96%, 96%, and 93%, respectively in normal, obese, and overweight patients. Overweight patients had significantly worse OS than normal ones (HR = 3.69, 95%CI = 1.82–4.53 p = 0.027) whereas no statistically significant differences were seen between obese and normal patients (HR 2.45, 95%CI = 0.68–8.78, p = 0.169). Conclusions: A lifestyle intervention can lead to clinically meaningful weight loss and increase PA in patients with BC. These results could contribute to improving the OS in obese patients compared to overweight ones. [ABSTRACT FROM AUTHOR]

We analyzed the impact of alloHSCT in a single center cohort of 89 newly diagnosed NPM1mut AML patients, consecutively treated according to the Northern Italy Leukemia Group protocol 02/06 [NCT00495287]. After two consolidation cycles, the detection of measurable residual disease (MRD) by RQ-PCR was strongly associated with an inferior three-year overall survival (OS, 45% versus 84%, p = 0.001) and disease-free survival (DFS, 44% versus 76%, p = 0.006). In MRD-negative patients, post-remissional consolidation with alloHSCT did not provide a significant additional benefit over a conventional chemotherapy in terms of overall survival [OS, 89% (95% CI 71–100%) versus 81% (95% CI 64–100%), p = 0.59] and disease-free survival [DFS, 80% (95% CI 59–100%) versus 75% (95% CI 56–99%), p = 0.87]. On the contrary, in patients with persistent MRD positivity, the three-year OS and DFS were improved in patients receiving an alloHSCT compared to those allocated to conventional chemotherapy (OS, 52% versus 31%, p = 0.45 and DFS, 50% versus 17%, p = 0.31, respectively). However, in this group of patients, the benefit of alloHSCT was still hampered by a high incidence of leukemia relapse during the first year after transplantation (43%, 95% CI 25–60%). Consolidative alloHSCT improves outcomes compared to standard chemotherapy in patients with persistent NPM1mut MRD positivity, but in these high-risk patients, the significant incidence of leukemia relapse must be tackled by post-transplant preemptive treatments. [ABSTRACT FROM AUTHOR]

Vulvar cancer (VC) is a rare disease of which recurrence poses management problems due to patients' advanced age and comorbidities, and to the localization of the disease. Palliative treatments, allowing local disease control in patients previously treated with multimodal therapies or with comorbidities, are lacking. In this study we tested electrochemotherapy (ECT) on recurrent VC refractory to standard therapies to assess the tumor response and to define the selection criteria for patient's candidate to ECT. This is a multicenter observational study carried out in five Italian centers. Data about patients and tumor characteristics, treatment, toxicity, and clinical response were recorded. In all procedures, intravenous bleomycin was administered according to European Standard Operative Procedure ECT (ESOPE) guidelines. Sixty-one patients, with a median age 79 years (range: 39–85) and mainly affected by squamous cellular carcinoma (91.8%), were treated with ECT. No serious adverse events were reported. Patients were discharged after three days (median, range: 0–8 days). Two months after ECT, the clinical response rate was 83.6% and was not related to age, body mass index, International Federation of Gynecology and Obstetrics (FIGO) stage, number of treated nodules, or previous treatments. ECT is a safe procedure with a favorable cost-effectiveness ratio and should be considered as a treatment option for local disease control in patients unsuitable for standard therapies. [ABSTRACT FROM AUTHOR]