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Rationale: Metastatic castration-resistant prostate cancer has a poor prognosis especially when harboring DNA damage repair gene mutations, nevertheless, in the case of pathogenic BRCA gene mutations, PARPi demonstrated a survival benefit and is a validated treatment. Nowadays, there is no data regarding unusual metastases after these drugs. Cutaneous metastases appear rarely in prostate cancer and were associated with a worse prognosis. Moreover, there are no consolidated data concerning skin tropism of prostate cancer cells, neither in the case of BRCA-associated cancers., Patient Concerns: Here, we report the case of a patient with a long history of BRCA1-mutated metastatic castration-resistant prostate cancer who developed a skin lesion on the scalp while on his fifth line of systemic therapy with olaparib. After a complete radical surgical excision, the pathology report showed prostate cancer localization., Diagnoses: A diagnosis of skin metastasis from prostate cancer was reported., Outcomes: The patient then continued olaparib therapy; after 7 months from excision, he experienced further bone and biochemical progression but not cutaneous progression., Lessons: A literature review of all reported cases of cutaneous metastasis in prostate cancer was conducted to shed light on the incidence, clinical presentation, diagnosis, treatment, and prognosis of this entity. We also reviewed published cases of skin metastasis in BRCA-associated cancers with an effort to correlate skin involvement with PARPi treatment, BRCAness status, and prognosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Benefits of early palliative care referral in oncology are well-validated. At the Veneto Institute of Oncology-IRCCS, a simultaneous-care outpatient clinic (SCOC) has been active since 2014, where patients with advanced cancer are evaluated by an oncologist together with a palliative care team. We prospectively assessed SCOC patients’ characteristics and SCOC outcomes through internal procedure indicators. Data were retrieved from the SCOC prospectively maintained database. There were 753 eligible patients. The median age was 68 years; primary tumor sites were gastrointestinal (75.2%), genitourinary (15.0%) and other sites (9.8%). Predominant symptoms were psychological issues (69.4%), appetite loss (67.5%) and pain (65.9%). Dyspnea was reported in 53 patients (7%) in the referral form, while it was detected in 226 patients (34.2%) during SCOC visits (p < 0.0001). Median survival of patients after the SCOC visit was 7.3 months. Survival estimates by the referring oncologist were significantly different from the actual survival. Psychological intervention was deemed necessary and undertaken in 34.6% of patients, and nutritional support was undertaken in 37.9% of patients. Activation of palliative care services was prompted for 77.7% of patients. Out of 357 patients whose place of death is known, 69.2% died at home, in hospice or residential care. With regard to indicators’ assessment, the threshold was reached for 9 out of 11 parameters (81.8%) requested by the procedure. This study confirmed the importance of close collaboration between oncologists and palliative care teams in responding properly to cancer patients’ needs. The introduction of a procedure with indicators allowed punctual assessment of a team’s performance.

Background: Perioperative FLOT (5-fluorouracil, oxaliplatin and docetaxel) has recently become the gold standard treatment for fit patients with operable gastric (GC) or gastroesophageal (GEJ) adenocarcinoma, getting a 5-year overall survival (OS) of 45%, over 23% with surgery alone., Methods: RealFLOT is an Italian, multicentric, observational trial, collecting data from patients with resectable GC or GEJ adenocarcinoma treated with perioperative FLOT. Aim of the study was to describe feasibility and safety of FLOT, pathological complete response rate (pCR), surgical outcomes and overall response rate (ORR) in an unselected real-world population. Additional analyses evaluated the correlation between pCR and survival and the prognostic role of microsatellite instability (MSI) status., Results: Of 206 patients enrolled that received perioperative FLOT at 15 Italian centers, 124 (60.2%) received at least 4 full-dose cycles, 190 (92.2%) underwent surgery, and 142 (68.9%) started the postoperative phase. Among patients who started the postoperative phase, 105 (51.0%) received FLOT, while 37 (18%) received de-intensified regimens, depending on clinical condition or previous toxicities. pCR was achieved in 7.3% of cases. Safety profile was consistent with literature. Neutropenia was the most common G 3-4 adverse event (AE): 19.9% in the preoperative phase and 16.9% in the postoperative phase. No toxic death was observed and 30-day postoperative mortality rate was 1.0%. ORR was 45.6% and disease control rate (DCR) was 94.2%. Disease-free survival (DFS) and OS were significantly longer in case of pCR (p = 0.009 and p = 0.023, respectively). A trend towards better DFS was observed among MSI-H patients., Conclusions: These real-world data confirm the feasibility of FLOT in an unselected population, representative of the clinical practice. pCR rate was lower than expected, nevertheless we confirm pCR as a predictive parameter of survival. In addition, MSI-H status seems to be a positive prognostic marker also in patients treated with taxane-containing triplets., (© 2021. The Author(s).)

Malnutrition and muscle wasting are frequently reported in cancer patients, either linked to the tumor itself or caused by oncologic therapies. Understanding the value of nutritional care during cancer treatment remains crucial. In fact, cancer-associated sarcopenia plays a key role in determining higher rates of morbidity, mortality, treatment-induced toxicities, prolonged hospitalizations and reduced adherence to anticancer treatment, worsening quality of life and survival. Planning baseline screening to intercept nutritional troubles earlier, organizing timely reassessments, and providing adequate counselling and dietary support, healthcare professional may positively interfere with this process and improve patients' overall outcomes during the whole disease course. Several screening tools have been proposed for this purpose. Nutritional Risk Screening (NRS), Mini Nutritional Assessment (MNA), Patient Generated Subjective Global Assessment (PG-SGA) are the most common studied. Interestingly, second-level tools including skeletal muscle index (SMI) and bioelectric impedance analysis (BIA) provide a more precise assessment of body composition, even if they are more complex. However, nutritional assessment is not currently used in clinical practice and procedures must be standardized in order to improve the efficacy of standard chemotherapy, targeted agents or even checkpoint inhibitors that is potentially linked with the patients' nutritional status. In the present review, we will discuss about malnutrition and the importance of an early nutritional assessment during chemotherapy and treatment with novel checkpoint inhibitors, in order to prevent treatment-induced toxicities and to improve survival outcomes.

The role of nutritional support for cancer patients in palliative care is still a controversial topic, in part because there is no consensus on the definition of a palliative care patient because of ambiguity in the common medical use of the adjective palliative. Nonetheless, guidelines recommend assessing nutritional deficiencies in all such patients because, regardless of whether they are still on anticancer treatments or not, malnutrition leads to low performance status, impaired quality of life (QoL), unplanned hospitalizations, and reduced survival. Because nutritional interventions tailored to individual needs may be beneficial, guidelines recommend that if oral food intake remains inadequate despite counseling and oral nutritional supplements, home enteral nutrition or, if this is not sufficient or feasible, home parenteral nutrition (supplemental or total) should be considered in suitable patients. The purpose of this narrative review is to identify in these cancer patients the area of overlapping between the two therapeutic approaches consisting of nutritional support and palliative care in light of the variables that determine its identification (guidelines, evidence, ethics, and law). However, nutritional support for cancer patients in palliative care may be more likely to contribute to improving their QoL when part of a comprehensive early palliative care approach.

Purpose: In metastatic colorectal cancer (MCRC), mucinous histology has been associated with poor response rate and prognosis. We investigated whether bevacizumab combined with different chemotherapy regimens may have an impact on clinical outcomes of MCRC patients with mucinous histology., Methods: 685 MCRC patients were classified in mucinous adenocarcinoma (MC) and non-mucinous adenocarcinoma (NMC) and were treated with first-line bevacizumab plus fluoropyrimidine (FP)-based, oxaliplatin (OXA)-based, irinotecan (IRI)-based, or FOLFOXIRI., Results: Ninety-four (13.7%) patients had MC. With a median follow-up of 50 months, MC patients had a median overall survival (OS) of 28.2 months compared with 27.7 months for the NMC group [hazard ratio (HR) = 0.92; 95% confidence interval (CI) 0.70-1.19, P = 0.530]. The overall response rates for MC and NMC were 41.5% (95% CI 31.5-51.4) and 62.4% (95% CI 58.4-66.3), respectively (Chi-square test, P <0.003). After correcting for significant prognostic factors by multivariate Cox regression analysis, age, resection of the primary tumour, and number of metastatic sites were found to be associated with poorer OS, but not mucinous histology., Conclusion: Compared with NMC, MCRC patients with mucinous histology treated with bevacizumab plus chemotherapy had comparable OS despite lower overall response rate.

One of the challenges during chemotherapy and radiotherapy is to complete the planned cycles and doses without dose-limiting toxicity. Growing evidence clearly demonstrates the relationship between dose-limiting toxicity and low muscle mass. Moreover, malnutrition leads to low performance status, impaired quality of life, unplanned hospital admissions, and reduced survival. In the past, the lack of clear and authoritative recommendations and guidelines has meant that oncologists have not always fully appreciated the importance of nutritional therapy in patients receiving anticancer treatments. Therefore, collaboration between oncologists and clinical nutrition specialists needs to be urgently improved. Recent guidelines from scientific societies and practical recommendations by inter-society consensus documents can be summarized as follows: 1) timely nutritional therapy should be carefully considered if patients undergoing anticancer treatments are malnourished or at risk of malnutrition due to inadequate oral intake; 2) if oral intake is inadequate despite counseling and oral nutritional supplements, supplemental enteral nutrition or, if this is not sufficient or feasible, parenteral nutrition should be considered; 3) home artificial nutrition should be prescribed and regularly monitored using defined protocols developed between oncologists and clinical nutrition specialists; 4) appropriate nutritional management in the context of simultaneous care should become a guaranteed right for all patients with cancer. The purpose of this review is to provide oncologists with an overview of the aims and current evidence about nutrition in oncology, together with updated practical and concise recommendations on the application of nutritional therapy in cancer patients receiving chemoradiotherapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Purpose: The international guidelines recommend the use of supplemental parenteral nutrition (SPN) in cancer patients when they are malnourished and hypophagic and where enteral nutrition is not feasible. However, there are limited data on the short-term effects of SPN in this patient population., Methods: The aim of this bicentric single-arm clinical trial (NCT02828150) was to evaluate the effects of early 7-day SPN on bioimpedance vectorial analysis (BIVA)-derived body composition, handgrip strength (HG), and serum prealbumin (PAB) in 131 hypophagic, hospitalized cancer patients at nutritional risk, with contraindications for enteral nutrition., Results: One hundred eighteen patients (90.1%) completed the 7-day SPN support regimen and 102 of them (86.4%) were in advanced disease stage. SPN induced a significant improvement of phase angle (PhA, + 0.25 [95% CI 0.11, 0.39]; p = 0.001), standardized phase angle (SPA, + 0.33 [95% CI 0.13, 0.53]; p = 0.002), HG (+ 2.1 kg -95% CI 1.30, 2.81]; p < 0.001), and PAB (+ 3.8 mg/dL [95% CI 2.1, 5.6]; p < 0.001). In multivariable analysis, the effects on BIVA parameters were more pronounced in patients (N = 90, 76.3%) in whom estimated protein and calorie requirements were both satisfied (adjusted difference: PhA, + 0.39 [95% CI 0.04, 0.73]; p = 0.030; SPA, + 0.62 [95% CI 0.16, 1.09]; p = 0.009). No significant changes in hydration status were detected and no severe metabolic or other complications occurred., Conclusions: Early 7-day SPN resulted in improved body composition, HG and PAB levels in hypophagic, and hospitalized cancer patients at nutritional risk in the absence of any relevant clinical complications. Further trials, aimed at verifying the efficacy of this early nutritional intervention on mid- and long-term primary clinical endpoints in specific cancer types, are warranted.

Objectives: Although gastric cancer (GC) incidence rises with age, older patients are poorly represented in clinical trials, whose results are therefore difficult to translate into standard management of older patients. Purpose of this study was to compare clinico-pathological features and survival outcomes between older and non-older patients with advanced GC treated with at least two chemotherapy lines., Materials and Methods: Clinico-pathological characteristics, basal values, and treatment data of older (≥70 years at second-line start) and non-older patients were compared using chi-square test or 2-tailed Fisher exact test. The Kaplan-Meier estimation was used to calculate progression-free survival (PFS) and overall survival (OS), which were examined by log-rank test., Results: Older patients represented 31.8% of the population (N = 868). Intestinal type was more frequent in older patients (P = .02). Poorly differentiated tumours were more often observed in non-older patients (P = .009). At stage IV diagnosis, the rate of liver metastases was higher in older patients (P = .02), while peritoneal spread was more represented in non-older patients (P = .002). Although older patients were more often treated with monotherapy (P = .001), they had similar PFS (HR 0.86, 95%CI 0.71-1.03, P = .102) and OS (HR 0.82, 95%CI 0.65-1.02, P = .08) compared to the non-older counterpart. No statistical differences were observed in treatment-related adverse events, hospital admissions, or further treatment lines between age groups., Conclusion: In our large cohort study, despite some differences in tumour characteristics and treatment intensity, no survival difference was found between older and non-older patients with advanced GC treated with at least two chemotherapy lines. Incidence of adverse events was similar between age groups., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Early palliative care (EPC) has shown a positive impact on quality of life (QoL), quality of care, and healthcare costs. We evaluated such effects in patients with advanced gastric cancer., Methods: In this prospective, multicenter study, 186 advanced gastric cancer patients were randomized 1:1 to receive standard cancer care (SCC) plus on-demand EPC (standard arm) or SCC plus systematic EPC (interventional arm). Primary outcome was a change in QoL between randomization (T0) and T1 (12 weeks after T0) in the Trial Outcome Index (TOI) scores evaluated through the Functional Assessment of Cancer Therapy-Gastric questionnaire. Secondary outcomes were patient mood, overall survival, and family satisfaction with healthcare and care aggressiveness., Results: The mean change in TOI scores from T0 to T1 was - 1.30 (standard deviation (SD) 20.01) for standard arm patients and 1.65 (SD 22.38) for the interventional group, with a difference of 2.95 (95% CI - 4.43 to 10.32) (p = 0.430). The change in mean Gastric Cancer Subscale values for the standard arm was 0.91 (SD 14.14) and 3.19 (SD 15.25) for the interventional group, with a difference of 2.29 (95% CI - 2.80 to 7.38) (p = 0.375). Forty-three percent of patients in the standard arm received EPC., Conclusions: Our results indicated a slight, albeit not significant, benefit from EPC. Findings on EPC studies may be underestimated in the event of suboptimally managed issues: type of intervention, shared decision-making process between oncologists and PC physicians, risk of standard arm contamination, study duration, timeliness of assessment of primary outcomes, timeliness of cohort inception, and recruitment of patients with a significant symptom burden., Clinical Trial Registration: ClinicalTrials.gov (NCT01996540).

Objectives: The aim of this study was to investigate the prevalence of cancer patients changing their diet in relation to cancer site, sex, age and geographic distribution. Furthermore, we aimed to explore the rationale behind dietary changes and to identify sources of information in order to plan specific educational training., Methods: Patients ≥18 y of age who accessed the Italian Cancer Patients, Families and Friends Association information points were invited to participate. An ad hoc self-report questionnaire was used. The questionnaire asked patients about changes made to the major food groups. A minimum sample of 100 patients for the most common cancers was planned. We analyzed 1257 questionnaires. We assessed the prevalence of, reasons for, and type of dietary changes. Logistic regression was used to analyze the main determinants of dietary changes., Results: Of the 1257 patients, 705 (56.1%) reported changes since receiving the diagnosis of cancer. On the logistic regression analysis, age and tumor site were significantly associated with dietary changes (P <0.001), mainly in patients <50 y of age and in those with upper gastrointestinal cancers. Slightly more than half (50.8%) of patients adopted a healthier diet, with 31.3% doing so to deal with eating-related side effects and 17.9% due to cancer sites. Regardless of the reasons for changing, the most common food items to result in a decrease in consumption were alcohol, red and processed meats, and sugary drinks. Only 15% of patients reported receiving specific nutrition indication., Conclusion: Italian patients are attentive to the importance of diet during cancer treatment. Personal choices reflect some indications for cancer prevention as there is still a shortage of guidelines for a correct diet during treatment. Nutrition indications are rarely given within the oncologic center., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The impact of free triiodothyronine (FT 3 )/free thyroxine (FT 4 ) ratio on survival in hospitalized geriatric patients was recently described. Up today, there are no data regarding the prognostic role of FT 3 /FT 4 ratio in patients with advanced cancer. We evaluated the impact of FT 3 /FT 4 ratio on survival in patients with refractory colorectal cancer (CRC) treated with regorafenib., Methods: Patients with metastatic CRC treated with regorafenib with available clinical data and baseline measurement of FT 3 , FT 4 , and thyroid-stimulating hormone (TSH) were considered eligible. Exploratory analyses included subjects treated at Istituto Oncologico Veneto. A confirmatory analysis was planned based on FT 3 /FT 4 ratio tertile results, and a validation cohort was built on data retrieved from University of Cagliari., Results: In an exploratory cohort, the median overall survival in patients with low, intermediate, and high FT 3 /FT 4 ratios, according to tertiles' value, was 4.8, 5.0, and 7.6 months, respectively (P = .003). The differences were significant in the multivariate model (hazard ratio, 0.43; 95% confidence interval, 0.28-0.68; P = .0003). Confirmatory results were obtained in a validation cohort, both in univariate (P = .0002) and in multivariate (hazard ratio, 0.56; 95% confidence interval, 0.36-0.88; P = .0118) models., Conclusions: High baseline FT 3 /FT 4 ratio is strongly associated to better outcome in patients with progressive metastatic CRC treated with regorafenib. Further investigations are ongoing to draw definitive conclusions regarding a potential predictive effect., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The cytotoxic agent, eribulin represents a new standard of care in the treatment of heavily pretreated metastatic breast cancer patients. Here, we describe our experience with eribulin in a patient with a controlled primary breast cancer, who showed an aggressive recurrence of the primary tumor, including metastatic disease. Treatment management of the second primary tumor included six lines of chemotherapy and three lines of hormonal therapy, including eribulin as sixth line among all chemotherapies received. Eribulin treatment achieved a fast response to all metastatic sites and decelerated the aggressive evolution of the second disease.

The structure-activity relationship (SAR) of 1,2,4-triazolo[1,5-a]-1,3,5-triazine derivatives related to ZM241385 as antagonists of the A(2A) adenosine receptor (AR) was explored through the synthesis of analogues substituted at the 5 position. The A(2A) AR X-ray structure was used to propose a structural basis for the activity and selectivity of the analogues and to direct the synthetic design strategy to provide access to solvent-exposed regions. Thus, we have identified a point of substitution for the attachment of solubilizing groups to enhance both aqueous solubility and physicochemical properties, maintaining potent interactions with the A(2A) AR and, in some cases, receptor subtype selectivity. Among the most potent and selective novel compounds were a long-chain ether-containing amine congener 20 (K(i) 11.5 nM) and its urethane-protected derivative 14 (K(i) 17.8 nM). Compounds 20 and 31 (K(i) 11.5 and 16.9 nM, respectively) were readily water-soluble up to 10 mM. The analogues were docked in the crystallographic structure of the hA(2A) AR and in a homology model of the hA(3) AR, and the per residue electrostatic and hydrophobic contributions to the binding were assessed and stabilizing factors were proposed.

Unlabelled: Superior sulcus tumour (SST) is an uncommon neoplasia whose optimal treatment remains controversial. Usually resected after induction RT or treated with definitive chemo-radiotherapy, it has recently aroused more interest because of preoperative chemo-radiotherapy. Treatment consisted of a platinum-based chemotherapy: carboplatin AUC 5 on days 1 and 22, combined with mitomycin-C 8 mg/m(2) on days 1 and 22, and vinblastine 4 mg/m(2) on days 1, 8, 22 and 29 (MVC) from 1994 to 1999, or combined with navelbine 25mg/m(2) on days 1, 8, 22 and 29 (NC), from 2000 to 2007. Radiotherapy was administered 5 days/week, 30 Gy in 10 fractions on days 22-35 (from 1994 to 1996), or 44 Gy in 22 fractions on days 22-52 (from 1997 to 2007). SURGERY was planned after 2-3 weeks since the completion of radiotherapy. Since 1994, 37 pts were treated with induction chemo-radiotherapy, 1 with induction radiotherapy only. Induction chemotherapy: 16 pts had MVC (43%) and 21 NC (57%); induction radiotherapy: 7 patients treated with MVC had 30 Gy/10F, 9 had 44 Gy/22F; all the patients treated with NC had 44 Gy/22F, but 2 of them did not complete radiotherapy because of early death (after 16 Gy/8F) and toxicity (after 38 Gy/19F). Grade 3-4 haematological toxicity of induction chemo-radiotherapy was found in 13 patients (35%); the most frequent non-haematological toxicities were constipation and oesophagitis. One complete, 18 partial and 8 minimal responses/stable disease were observed. Moreover, 1 progression disease and 1 early death occurred., Surgery: 30 upper lobectomies (17 right, 13 left) and 4 segmentectomies, with chest wall resections, were performed (89% resection rate); 4 pts were not operated. Radical resections were achieved in 74% of the patients, with 5 pathologic complete remissions at resection. Twenty-seven patients (71%) had improvement of shoulder/arm pain. Median progression-free survival was 64 weeks and median survival was 148 weeks. The 5-year overall and progression-free survivals were 40% and 29%, respectively. In the multimodality treatment of SST, concurrent carboplatin-based chemotherapy plus radiotherapy were active and feasible without major toxicities. This resulted in high resectability rate and favourable progression-free and overall survival rates., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study was to examine in vitro, by means of kinetic analysis and molecular docking simulations, the effects of the flavone diosmetin and its flavanone analog hesperetin on CYP (cytochrome P450) 2C9-mediated drug metabolism. To this purpose, the conversion of diclofenac to 4'-hydroxydiclofenac by human liver microsomes was used as a model assay for assessing the CYP2C9 inhibitory activity of these two flavonoids. Kinetic analyses showed that diosmetin and hesperetin were reversible, dead-end inhibitors of 4'-hydroxydiclofenac formation; their mean K(i) (inhibitor dissociation constant) values were 1.71 ± 0.58 and 21.50 ± 3.62 µM, respectively. Diosmetin behaved as a competitive inhibitor, since it increased markedly the K(m) (substrate concentration yielding 50% of V(max)) of the reaction without affecting the V(max) (maximum velocity of reaction). Hesperetin modified markedly K(m) and to a lesser extent also modified V(max), thus acting as a mixed competitive-noncompetitive inhibitor. The results of molecular docking simulations were consistent with those of kinetic analysis, since they showed that the putative binding sites of both diosmetin and hesperetin coincided with the CYP2C9 substrate binding site. The demonstration that diosmetin and hesperetin inhibit CYP2C9-mediated diclofenac metabolism at low micromolar concentrations is of potential clinical relevance because CYP2C9 is responsible for the biotransformation of various therapeutically important drugs that have narrow therapeutic indexes.

The hypothesis that increasing cytotoxic dose intensity will improve cancer cure rates is compelling. Although supporting evidence for this hypothesis has accrued for several tumor types, including lymphomas, breast cancer, and testicular cancers, it remains unproven. Small-cell lung cancer is extremely chemo- and radiosensitive, with a response rate of 80% achieved routinely, but few patients are cured by chemoradiotherapy. In this setting, increased cytotoxic dose intensity might improve cure rates. The finding that response rates in small-cell lung cancer correlate with received cytotoxic dose intensity merely confirms that "less is worse" and "more is better." Within conventional ranges, dose intensity can be increased with the support of hematopoietic growth factors and/or by shortening treatments intervals; however, dose intensity could be increased by only 20%-30%, and a survival advantage has not been clearly demonstrated. Given its high chemosensitivity, small-cell lung cancer was one of the first malignancies deemed suitable for increasing dose intensity and even for the use of a megadose with the support of autologous bone marrow transplantation. Some interest is emerging again due to improvements in supportive care, such as the availability of hematopoietic growth factors and peripheral blood progenitor cells.