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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: 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: Lung cancer is a heterogeneous group of diseases in both morphology and molecular subtypes. There are two main histological categories of lung cancer: small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Although overall lung cancer mortality is declining in Italy, little is known about mortality trends by cancer subtype at the population level because death certificates do not record subtype information. This observational epidemiological study, using data from the Reggio Emilia Cancer Registry, evaluated the incidence, mortality, and survival trends of lung cancer according to the specific subtype. This study confirms the decline in the incidence and mortality of lung cancer in males, mainly squamous cell forms, inversely associated with cigarette smoking and the introduction of new drugs since 2013. This study assessed the incidence, mortality, and survival of lung cancer subtypes of NSCSLC (non-small-cell lung cancer), SCLC (small-cell lung cancer), and other morphologies. It is an observational epidemiological study using 7197 cases from the Reggio Emilia Cancer Registry recorded between 2001 and 2020 in males and females. The incidence of NSCLC in 5104 males indicates a significant 3% annual increase until 2013 and then a decline of −3.2% that is not statistically significant; until 2014, mortality increased significantly (3.2%), but it then decreased non-significantly (−12.1%), especially squamous cell cancer. In 2093 females, the incidence and mortality trends continued to rise significantly through 2012, and then they began to slightly decline (not statistically significant). The two-year relative survival of NSCLC increased from 32% to 38% in males and from 42% to 56% in females. SCLC in males decreased significantly both in incidence and mortality, while in women, it showed a slight increase (significantly for incidence but not for mortality). This study is important because it analyzes the decrease in lung cancer in males and the increase in females in relation to the different histotypes. Our study's findings confirmed a decline in male incidence and death beginning in 2013. We were unable to determine if the drop in cigarette smoking and the introduction of new drugs such as EGFR in first-line therapy were responsible for the lower incidence. [ABSTRACT FROM AUTHOR]

Simple Summary: The malignant transformation risk of oral lichen planus (OLP) is still a dilemma in the literature. The first report of oral squamous cell carcinoma with the origin of OLP was in 1910. Initially, the reported risk in the literature was high after this date; then, with the application of restricted criteria for the diagnosis of OLP, the reported risk become too low. Currently, there is a recommendation to conduct further studies in which other variables are considered, such as smoking and drinking habits and the type and localization of the lesion. This is in order to evaluate the exact risk of OLP and, correspondingly, to avoid the clinical underestimation by medical staff of the risk of malignant transformation of OLP. This study aims to retrospectively assess the potential risk of malignant transformation in patients with diagnosed oral lichen planus (OLP) between 2015 and 2022, and to evaluate the influence of different risk factors. The department's database and medical records from 2015 to 2022 were searched for patients with a confirmed diagnosis of OLP based on both clinical and histological parameters. A total of 100 patients (59 females and 41 males) were found with a mean age of 64.03 years. In the considered period, the percentage of diagnosed OLP patients was 1.6%, while the percentage of diagnosed OLP patients with transformation to oral squamous cell carcinoma (OSCC) was 0.18%. A statistically significant difference was found with age (p = 0.038), tobacco status (p = 0.022), and radiotherapy (p = 0.041). The analysis revealed the presence of significant risk in ex-smokers (>20 pack-years), with an odds ratio (OR) of 10.0000 (95% confidence interval (95% CI) 1.5793–63.3186); in alcohol-drinker patients, with an OR of 4.0519 (95% CI 1.0182–16.1253); in ex-smoker and alcohol-drinker patients, with OR of 17.6250 (95% CI 2.2464–138.2808); and in patients who had undergone radiotherapy, with OR of 6.3000 (95% CI 1.2661–31.3484). The malignant transformation of oral lichen planus was slightly higher than thought, and the results revealed a possible association with age, tobacco and alcohol status, and history of radiotherapy. An elevated risk of malignant transformation was observed in heavy ex-smoker patients, alcohol-drinker patients, and alcohol-drinker patients with a history of smoking (ex-smokers). Persuading the patient to quit tobacco and alcohol consumption and periodic follow-ups are recommended in general, but particularly in the presence of these risk factors. [ABSTRACT FROM AUTHOR]

Simple Summary: National cancer registry data showed that segmental ureterectomy is not associated with inferior survival compared to radical nephroureterectomy in upper-tract urothelial carcinoma patients. Segmental ureterectomy provides a valid surgical approach that does not meaningfully sacrifice survival outcomes within appropriately selected patients of upper urothelial carcinoma of the ureter. Given the potential renal functional preservation benefits, segmental ureterectomy should be considered for selected patients, especially if there is an increased probability of requiring adjuvant chemotherapy. Segmental ureterectomy (SU) is an alternative to radical nephroureterectomy (RNU) in the treatment of upper-tract urothelial carcinoma (UTUC) of the ureter. SU generally preserves renal function, at the expense of less intensive cancer control. We aim to assess whether SU is associated with inferior survival compared to RNU. Using the National Cancer Database (NCDB), we identified patients diagnosed with localized UTUC of the ureter between 2004–2015. We used a propensity-score-overlap-weighted (PSOW) multivariable survival model to compare survival following SU vs. RNU. PSOW-adjusted Kaplan–Meier curves were generated and we performed a non-inferiority test of overall survival. A population of 13,061 individuals with UTUC of the ureter receiving either SU or RNU was identified; of these, 9016 underwent RNU and 4045 SU. Factors associated with decreased likelihood of receiving SU were female gender (OR, 0.81; 95% CI, 0.75–0.88; p < 0.001), advanced clinical T stage (cT4) (OR, 0.51; 95% CI, 0.30–0.88; p = 0.015), and high-grade tumor (OR, 0.76; 95% CI, 0.67–0.86; p < 0.001). Age greater than 79 years was associated with increased probability of undergoing SU (OR, 1.18; 95% CI, 1.00–1.38; p = 0.047). There was no statistically significant difference in OS between SU and RNU (HR, 0.98; 95% CI, 0.93–1.04; p = 0.538). SU was not inferior to RNU in PSOW-adjusted Cox regression analysis (p < 0.001 for non-inferiority). In weighted cohorts of individuals with UTUC of the ureter, the use of SU was not associated with inferior survival compared to RNU. Urologists should continue to utilize SU in appropriately selected patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy revolutionized the treatment of cutaneous melanoma and greatly improved treatment outcomes in this group of patients. Mucosal melanoma is a rare disease, biologically distinct from the cutaneous subtype. There is little real-world data on immunotherapy efficacy in mucosal melanoma. Therefore, we aimed to analyze and describe experiences in mucosal melanoma treatment in five high volume oncology centers in Europe. Furthermore, we evaluated if concomitant radiotherapy may improve the outcomes of these patients. We conclude that immunotherapy with anti-PD1 antibodies is a safe and effective treatment of mucosal melanoma. Concomitant radiotherapy may be beneficial in a selected subgroup of patients with advanced mucosal melanoma. Mucosal melanoma is a rare disease epidemiologically and molecularly distinct from cutaneous melanoma developing from melanocytes located in mucosal membranes. Little is known about its therapy. In this paper, we aimed to evaluate the results of immunotherapy and radiotherapy in a group of patients with advanced mucosal melanoma, based on the experience of five high-volume centers in Poland and Italy. There were 82 patients (53 female, 29 male) included in this retrospective study. The median age in this group was 67.5 (IQR: 57.25–75.75). All patients received anti-PD1 or anti-CTLA4 antibodies in the first or second line of treatment. Twenty-three patients received radiotherapy during anti-PD1 treatment. In the first-line treatment, the median progression-free survival (PFS) reached six months in the anti-PD1 group, which was statistically better than 3.1 months in the other modalities group (p = 0.004). The median overall survival (OS) was 16.3 months (CI: 12.1–22.3) in the whole cohort. Patients who received radiotherapy (RT) during the anti-PD1 treatment had a median PFS of 8.9 months (CI: 7.4–NA), whereas patients treated with single-modality anti-PD1 therapy had a median PFS of 4.2 months (CI: 3.0–7.8); this difference was statistically significant (p = 0.047). Anti-PD1 antibodies are an effective treatment option in advanced mucosal melanoma (MM). The addition of RT may have been beneficial in the selected subgroup of mucosal melanoma patients. [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: After breast and prostate cancer, colorectal (CRC) is the third most frequent cancer in men and women. It is unclear if protein-rich diets other than red meat elevate risk or even lower CRC occurrence at specific colon locations. The aim of this study is to assess the associations of animal and plant protein intakes with CRC risk in middle-aged Italian men and women. Our findings show that replacing animal proteins with plant proteins was associated with a lower risk of rectal cancer but not of colon cancer, while replacing animal proteins with plant-based proteins from high-glycemic-index (GI) foods was associated with an increased colon cancer risk. These results have important public health implications as they suggest that both refined high-GI foods and meat might have site-specific roles in the pathogenesis of CRC. We prospectively investigated the associations of protein intake with colorectal cancer (CRC) risk in middle-aged Italian men and women. Food consumption was assessed by validated Epic semiquantitative food-frequency questionnaires. Multivariable Cox models stratified by center, age, and sex, adjusted for confounders, estimated the associations of animal and plant protein consumption with CRC risk by subsite. Among 44,824 men and women, we identified 539 incident CRCs after a median follow-up of 14 years. Replacing animal proteins with plant proteins was associated with a decreased risk of rectal (HR, 0.71; 95% CI, 0.55–0.92) but not colon cancer. By contrast, replacing animal proteins with plant proteins from high-glycemic-index (GI) foods was associated with an increased risk of proximal and distal (including sigma) colon cancer (HR, 1.23; 95% CI, 1.07–1.40) but not when animal proteins were replaced with plant proteins from low-GI foods (HR, 0.93; 95% CI, 0.79–1.11). Further evaluation revealed that the increased colon cancer risk was limited to the substitution of proteins from red and processed meat, as well as dairy and eggs, with vegetable proteins from high-GI foods. Participants in the highest quintile of animal protein intake had higher plasma glucose and cholesterol levels than those in the lowest quintile. By contrast, higher intake of plant proteins from low-GI foods was inversely associated with fasting insulin and HOMA-IR levels. In conclusion, replacing animal proteins with plant proteins from high-GI foods was associated with an increased risk of colon cancer. [ABSTRACT FROM AUTHOR]

Abstract: Immunohistochemical loss of the succinate dehydrogenase subunit B (SDHB) has recently been reported as a surrogate biomarker of malignancy in sporadic and familial pheocromocytomas and paragangliomas through the activation of hypoxia pathways. However, data on the prevalence and the clinical implications of SDHB immunoreactivity in ileal neuroendocrine tumors are still lacking. Thirty-one consecutive, advanced primary midgut neuroendocrine tumors and related lymph node or liver metastases from 24 males and seven females were immunohistochemically assessed for SDHB. All patients were G1 tumors (Ki-67 labeling index ⩽2%). SDHB immunohistochemistry results were expressed as immunostaining intensity and scored as low or strong according to the internal control represented by normal intestinal cells. Strong positivity for SDHB, with granular cytoplasmatic reactivity, was found in 77% of primary tumors (T), whilst low SDHB expression was detected in 90% of metastases (M). The combined analysis (T+M) confirmed the loss of SDHB expression in 82% of metastases compared to 18% of primary tumors. SDHB expression was inversely correlated with Ki-67 labeling index, which accounted for 1.54% in metastastic sites and 0.7% in primary tumors. A correlation between SDHB expression loss, increased Ki-67 labeling index and biological aggressiveness was shown in advanced midgut neuroendocrine tumors, suggesting a role of tumor suppressor gene. [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]

Simple Summary: Our study investigated DNA methylation differences in easily accessible white blood cells (WBCs) between malignant pleural mesothelioma (MPM) cases and asbestos-exposed cancer-free controls. A multiple regression model highlighted that the methylation level of two single CpGs (cg03546163 in FKBP5 and cg06633438 in MLLT1) are independent MPM markers. The epigenetic changes at the FKBP5 and MLLT1 genes were robustly associated with MPM in asbestos-exposed subjects. Interaction analyses showed that MPM cases and cancer-free controls showed DNAm differences which may be linked to asbestos exposure. Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive tests aimed at an MPM risk assessment tool that might improve life expectancy. Three hundred asbestos-exposed subjects (163 MPM cases and 137 cancer-free controls), from the same geographical region in Italy, were recruited. The evaluation of asbestos exposure was conducted considering the frequency, the duration and the intensity of occupational, environmental and domestic exposure. A genome-wide methylation array was performed to identify novel blood DNA methylation (DNAm) markers of MPM. Multiple regression analyses adjusting for potential confounding factors and interaction between asbestos exposure and DNAm on the MPM odds ratio were applied. Epigenome-wide analysis (EWAS) revealed 12 single-CpGs associated with the disease. Two of these showed high statistical power (99%) and effect size (>0.05) after false discovery rate (FDR) multiple comparison corrections: (i) cg03546163 in FKBP5, significantly hypomethylated in cases (Mean Difference in beta values (MD) = −0.09, 95% CI = −0.12|−0.06, p = 1.2 × 10−7), and (ii) cg06633438 in MLLT1, statistically hypermethylated in cases (MD = 0.07, 95% CI = 0.04|0.10, p = 1.0 × 10−6). Based on the interaction analysis, asbestos exposure and epigenetic profile together may improve MPM risk assessment. Above-median asbestos exposure and hypomethylation of cg03546163 in FKBP5 (OR = 20.84, 95% CI = 8.71|53.96, p = 5.5 × 10−11) and hypermethylation of cg06633438 in MLLT1 (OR = 11.71, 95% CI = 4.97|29.64, p = 5.9 × 10−8) genes compared to below-median asbestos exposure and hyper/hypomethylation of single-CpG DNAm, respectively. Receiver Operation Characteristics (ROC) for Case-Control Discrimination showed a significant increase in MPM discrimination when DNAm information was added in the model (baseline model, BM: asbestos exposure, age, gender and white blood cells); area under the curve, AUC = 0.75; BM + cg03546163 at FKBP5. AUC = 0.89, 2.1 × 10−7; BM + cg06633438 at MLLT1. AUC = 0.89, 6.3 × 10−8. Validation and replication procedures, considering independent sample size and a different DNAm analysis technique, confirmed the observed associations. Our results suggest the potential application of DNAm profiles in blood to develop noninvasive tests for MPM risk assessment in asbestos-exposed subjects. [ABSTRACT FROM AUTHOR]

Simple Summary: The analyses presented, based on data from the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study, evaluated patients' reported quality of life outcomes related to bowel function and bother over a 2-year period from the diagnosis. Growth mixture models were considered for patients who underwent radiotherapy, including treatments that were associated or not associated with androgen deprivation therapy. Our data revealed that the proportion of patients that were radiotherapy-treated with persisting significant bowel worsening at the 24 months interval is very limited. The absence of comorbidities and the use of intensity or volumetric radiotherapy techniques with image guidance were found to be related with a better tolerance to radiotherapy in terms of bowel side effects. These findings could be relevant for treatment selection and accurate patient information. Radiotherapy (RT) represents an important therapeutic option for the treatment of localized prostate cancer. The aim of the current study is to examine trajectories in patients' reported quality of life (QoL) aspects related to bowel function and bother, considering data from the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study, analyzed with growth mixture models. Data for patients who underwent RT, either associated or not associated with androgen deprivation therapy, were considered. QoL outcomes were assessed over a 2-year period from the diagnosis, using the Italian version of the University of California Los Angeles-Prostate Cancer Index (Italian-UCLA-PCI). Three trajectories were identified for the bowel function; having three or more comorbidities and the use of 3D-CRT technique for RT were associated with the worst trajectory (OR = 3.80, 95% CI 2.04–7.08; OR = 2.17, 95% CI 1.22–3.87, respectively). Two trajectories were identified for the bowel bother scores; diabetes and the non-Image guided RT method were associated with being in the worst bowel bother trajectory group (OR = 1.69, 95% CI 1.06–2.67; OR = 2.57, 95% CI 1.70–3.86, respectively). The findings from this study suggest that the absence of comorbidities and the use of intensity modulated RT techniques with image guidance are related with a better tolerance to RT in terms of bowel side effects. [ABSTRACT FROM AUTHOR]

Background: The incidence and prognosis of SARS-CoV-2-positive cancer patients on active oncologic treatment remain unknown. Retrospective data from China reported higher incidence and poorer outcomes with respect to the general population. We aimed to describe the real-word incidence of SARS-CoV-2 in cancer patients and the impact of oncologic therapies on the infection. Materials & Methods: In this study, we analysed all consecutive cancer patients with solid tumours undergoing active intravenous treatment (chemotherapy, immunotherapy, targeted therapy, alone or in combination) between 21 February and 30 April 2020, in a high-volume cancer centre in Lombardy, Italy. We focused on SARS-CoV-2-positive patients, reporting on the clinical characteristics of the cancer and the infection. Results: We registered 17 SARS-CoV-2-positive patients among 1267 cancer patients on active treatment, resulting in an incidence of 1.3%. The median age was 69.5 years (range 43–79). Fourteen patients (82%) required hospitalisation for COVID-19 with a median in-hospital stay of 11.5 days (range 3–58). Fourteen of the seventeen (82%) were treated for locally advanced or metastatic disease. We could not demonstrate any correlation between SARS-CoV-2 infection and tumour or treatment type. The COVID-19-related fatality rate was 29% (5/17), which was higher than that of the general population cared for in our centre (20%). Conclusions: Active oncologic treatments do not represent a risk factor for SARS-CoV-2 infection in cancer patients. However, the prognosis of infected cancer patients appears to be worse compared with that of the non-oncologic population. Given the low number of SARS-CoV-2-positive cases and the uncertainties in risk factors that may have an impact on the prognosis, we advocate for the continuum of cancer care even during the current pandemic. [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]