Allies not enemies-creating a more empathetic and uplifting patient experience through technology and art.

OBJECTIVE: To understand whether art and technology (mainly conversational agents) may help oncology patients to experience a more humanized journey. METHODS: This narrative review encompasses a comprehensive examination of the existing literature in this field by a multicenter, multidisciplinary, and multiprofessional team aiming to analyze the current developments and potential future directions of using art and technology for patient engagement. RESULTS: We identified three major themes of patient engagement with art and three major themes of patient engagement with technologies. Two real-case scenarios are reported from our experience to practically envision how findings from the literature can be implemented in different contexts. CONCLUSION: Art therapy and technologies can be ancillary supports for healthcare professionals but are not substitutive of their expertise and responsibilities. Such tools may help to convey a more empathetic and uplifting patient journey if properly integrated within clinical practice, whereby the humanistic touch of medicine remains pivotal.

Outcomes and Prognostic Factors of Patients with Unresectable or Metastatic Esophageal Squamous Cell Carcinoma Undergoing Immunotherapy- Versus Chemotherapy-Based Regimens: Systematic Review and Pooled Analyses.

OBJECTIVE: Immunotherapy-based regimens (IMT) versus cytotoxic chemotherapy (CHT) improved overall survival (OS) of patients with unresectable or metastatic esophageal squamous cell carcinoma (mESCC), but the role of prognostic variables is unclear. The study aims to explore the interaction of prognostic factors with survival after IMT or CHT. METHODS: A systematic review was performed to select trials comparing IMT and CHT regimens in mESCC patients. A meta-analysis of upfront IMT + CHT vs. CHT trials evaluated the overall effect size and heterogeneity between studies. In view of the expected differences between chemotherapy and immunotherapy on the survival curve, to better explore the effect of any prognostic variables on OS, before and after progression, the treatment arms were evaluated as independent cohorts, and ten baseline variables were extracted and assessed by linear regression. RESULTS: Fourteen trials were identified. Seven studies compared upfront CHT + IMT vs. CHT documenting longer OS for CHT + IMT (HR 0.69, CI 0.65-0.72), without heterogeneity (Q = 1.43, p value = 0.968) or differences in the most represented subgroups. Twenty-nine study cohorts were selected from the 14 trials. Median OS and PPS, but not PFS, were significantly increased after IMT compared with CHT. The analysis of baseline variables after CHT documented a favorable prognostic effect for advanced age (ß = 0.768, p value = 0.016), involvement of 0-1 metastasis sites (ß = 0.943, p value = 0.005), and absence of previous radiation therapy (ß = - 0.939, p value = 0.006), while none of them influenced prognosis after IMT. CONCLUSION: The introduction of upfront IMT prolonged mESCC patients OS, mostly improving the outcomes of young patients, with multiple metastasis sites and without previous radiotherapy.

Effect of Subgroups on Study Outcomes in Unresectable Hepatocellular Carcinoma Undergoing Upfront Systemic Treatment: A Meta-analysis.

OBJECTIVES: Immunotherapy improved the outcome of patients with unresectable hepatocellular carcinoma, but not all studies are in agreement, nor is it clear whether certain subgroups have really benefited. This study aims to perform an updated meta-analysis of trials comparing upfront immunotherapy-based regimens versus tyrosin-kinase inhibitors, and some exploratory analyses. METHODS: After a systematic review, randomized trials of immunotherapy-based regimens versus tyrosin-kinase inhibitors were selected. A meta-analysis assessed the relationship between treatment arm and overall survival. Based on the resulting heterogeneity, a further investigation of 11 variables by meta-regression and an exploration of subgroups were planned. RESULTS: Eight studies were selected. From the meta-analysis, the overall survival improvement for the immunotherapy-based arms was consistent (HR: 0.77, CI: 0.68-0.88), although heterogeneity between studies was significant ( Q =16.37; P =0.0373; I2 =51.1%). After meta-regression, the effect of the experimental arm was more pronounced in the elderly and lost among patients with HCV-related liver disease. Subgroups suggested a favorable effect of immunotherapy in patients with HBV-related hepatocellular carcinoma, extrahepatic dissemination, and elevated alpha-fetoprotein. CONCLUSION: The study results confirm the significant overall survival improvement after immunotherapy-based regimens but suggest different effects on the outcome depending on age, etiology of liver disease, and tumor burden.

The importance of integrated therapies on cancer: Silibinin, an old and new molecule.

In the landscape of cancer treatments, the efficacy of coadjuvant molecules remains a focus of attention for clinical research with the aim of reducing toxicity and achieving better outcomes. Most of the pathogenetic processes causing tumour development, neoplastic progression, ageing, and increased toxicity involve inflammation. Inflammatory mechanisms can progress through a variety of molecular patterns. As is well known, the ageing process is determined by pathological pathways very similar and often parallel to those that cause cancer development. Among these complex mechanisms, inflammation is currently much studied and is often referred to in the geriatric field as 'inflammaging'. In this context, treatments active in the management of inflammatory mechanisms could play a role as adjuvants to standard therapies. Among these emerging molecules, Silibinin has demonstrated its anti-inflammatory properties in different neoplastic types, also in combination with chemotherapeutic agents. Moreover, this molecule could represent a breakthrough in the management of age-related processes. Thus, Silibinin could be a valuable adjuvant to reduce drug-related toxicity and increase therapeutic potential. For this reason, the main aim of this review is to collect and analyse data presented in the literature on the use of Silibinin, to better understand the mechanisms of the functioning of this molecule and its possible therapeutic role.

Radiographic and serologic response in patients with unresectable hepatocellular carcinoma receiving systemic antineoplastic treatments: A trial-level analysis.

BACKGROUND: In a disease like unresectable hepatocellular carcinoma, overall survival is an inadequate outcome measure for evaluating the effectiveness of treatments given the high risk of death from liver failure. There is an unmet need for reliable alternative end points for clinical trials and daily clinical practice. To evaluate treatment response in patients with unresectable or metastatic hepatocellular carcinoma (mHCC), imaging-related end points are often used, whereas serologic end points have been developed for patients with serum alpha-fetoprotein levels >20 ng/mL. The objective of this study was to evaluate clinical trials that report concomitant assessment of radiographic and serologic response in patients with mHCC. METHODS: After a systematic review, studies that evaluated response according to radiographic and serologic criteria were selected. A correlation between progression-free survival (PFS) and overall survival (OS) was performed, and a linear regression of each response-related outcome measure with OS was reported. Finally, the effect of eight baseline variables on OS and response-related measures was evaluated. RESULTS: Twenty-six studies were included, including 16 first-line studies and 10 second-line studies. PFS and response rates demonstrated a significant relationship with OS, whereas disease control rates did not. The responses were correlated with OS, particularly in the first-line setting, after targeted therapy, and whenever assessment was early. Among the baseline variables, only performance status had a prognostic role, whereas hepatitis B virus-related liver disease was associated with higher radiographic response rates. CONCLUSIONS: PFS and radiographic and serologic response rates appear to be reliable intermediate end points in patients with mHCC who are undergoing systemic antineoplastic therapy. However, the serologic response is available earlier.

Prognostic Effect of Performance Status on Outcomes of Patients with Colorectal Cancer Receiving First-Line Chemotherapy: A Meta-analysis.

BACKGROUND: Performance status (PS) is a variable derived from the assessment of a patient's functional status, originally proposed to predict drug toxicity. However, despite its characteristic of being subjective and unidimensional, it has become one of the most important prognostic variables for patients with metastatic colorectal cancer (mCRC). In light of the considerable progressive prolongation of median overall survival (OS) of patients with mCRC, it is unclear whether PS continues to be a valid prognostic factor. This article aims to perform a meta-analysis to verify the current prognostic role of PS. METHODS: A search on two databases of prospective trials of first-line chemotherapy in mCRC patients, published in English from 1991 to 2020, was done by predefined criteria. After the selection of phase III trials evaluating the prognostic role of PS, a meta-analysis has been performed. RESULTS: Thirteen trials were included in the meta-analysis. They reported a reduction in the risk of death with a PS 0 compared to a PS 1 or more (HR 0.63, CI 0.54-0.72; 13 studies), which was confirmed for the comparison between PS 0 and PS 1. However, the study found significant heterogeneity (Q = 68.10; p-value < 0.001) and high-grade inconsistency (I2 = 82.38%). Therefore, to explore the reasons for the heterogeneity, a univariate meta-regression was performed, which suggested a possible moderating activity for liver metastases and timing of metastasis. CONCLUSIONS: PS is a reliable prognostic factor for patients with mCRC receiving first-line chemotherapy but is poorly evaluated in phase III trials.

The Impact of HAPPY (Humanity Assurance Protocol in Interventional Radiotherapy) on the Psychological Well-being of Gynecological Cancer Patients.

BACKGROUND: HAPPY (Humanity Assurance Protocol in interventional radiotherapy) reports the necessity for gynecological cancer patients to undergo interventional radiotherapy (IRT, also called brachytherapy). The present paper has evaluated how some precautions may improve the psychological well-being of the patients during IRT. METHODS: Patients with gynecological cancer undergoing IRT-HDR were analyzed. Patients answered three questionnaires before the IRT procedure (T0) and at the end of IRT (T1): Distress Thermometer (DT), Numerical Rating Scale for IRT procedure distress (NRS), and Hospital Anxiety and Depression Scale (HADS). Correlations have been calculated pairwise through pandas. corrwith with a Pearson algorithm, and the p-values have been calculated through scipy.stats.pearsonr. Plots have been generated through seaborn and matplotlib. A Wilcoxon test was used. RESULTS: 55 patients were selected for this study. The median age of the patients was 64 (range, 39-84) years. 52 patients were with stage I endometrial cancer, whereas 3/3 patients with cervical cancer had locally advanced stages (IIB-IVA). 26 patients had a high education level (47.3%), and 38 were married or with a partner (69.1%). Only 14/55 (25.45%) patients were working. The HADS, DT, and NRS averages before the IRT procedure (T0) were 10.2, 3.8, and 4.3, respectively. After applying the HAPPY protocol, the HADS, DT, and NRS averages after IRT (T1) were 9.4, 3.4, and 2.6, respectively. The Wilcoxon signed rank test analysis showed a significant improvement in NRS (p < 0.00001) and HADS (p = 0.034). Living with a partner, parents or relatives was the only parameter statistically significantly associated with better DT pre-IRT (p = 0.04), HADS pre-IRT (p = 0.01), DT post-IRT (p = 0.01), and HADS post-IRT (p = 0.04). CONCLUSION: In our study, the HAPPY protocol was associated with a significant reduction in patients' distress, anxiety, and discomfort.

Sarcopenia Diagnosis and Management in Hematological Malignancies and Differences with Cachexia and Frailty.

Sarcopenia is a geriatric syndrome characterized by a progressive loss of systemic muscle mass and decreased muscle strength or physical function. Several conditions have a role in its pathogenesis, significantly impacting adverse outcomes such as falls, functional decline, frailty, disability, multiple hospitalizations, and mortality. In the oncological setting, sarcopenia is associated with an increased risk of treatment toxicity, postoperative complications, and a higher mortality rate related to other causes (e.g., pneumonia). In the hematological field, even more so, sarcopenia predicts toxicity and response to treatments. In patients with hematologic malignancy, low muscle mass is associated with adverse outcomes and is a predictor of overall survival and non-relapse mortality. Therefore, it is essential to correctly recognize sarcopenia, evaluate the risk factors and their impact on the patient's trajectory, and effectively treat sarcopenia. Sarcopenia is a reversible condition. The most effective intervention for reversing it is physical exercise combined with nutrition. The objective of clinical assessment focused on sarcopenia is to be able to carry out a "tailor-made treatment".

KIT 1 (Keep in Touch) Project-Televisits for Cancer Patients during Italian Lockdown for COVID-19 Pandemic: The Real-World Experience of Establishing a Telemedicine System.

To evaluate the adoption of an integrated eHealth platform for televisit/monitoring/consultation during the COVID-19 pandemic. METHODS: During the lockdown imposed by the Italian government during the COVID19 pandemic spread, a dedicated multi-professional working group was set up in the Radiation Oncology Department with the primary aim of reducing patients' exposure to COVID-19 by adopting de-centralized/remote consultation methodologies. Each patient's clinical history was screened before the visit to assess if a traditional clinical visit would be recommended or if a remote evaluation was to be preferred. Real world data (RWD) in the form of patient-reported outcomes (PROMs) and patient reported experiences (PREMs) were collected from patients who underwent televisit/teleconsultation through the eHealth platform. RESULTS: During the lockdown period (from 8 March to 4 May 2020) a total of 1956 visits were managed. A total of 983 (50.26%) of these visits were performed via email (to apply for and to upload of documents) and phone call management; 31 visits (1.58%) were performed using the eHealth system. Substantially, all patients found the eHealth platform useful and user-friendly, consistently indicating that this type of service would also be useful after the pandemic. CONCLUSIONS: The rapid implementation of an eHealth system was feasible and well-accepted by the patients during the pandemic. However, we believe that further evidence is to be generated to further support large-scale adoption.

Myocardial bridge in a patient with castration-resistant metastatic prostate cancer treated with enzalutamide.

INTRODUCTION: Myocardial bridge is a morphological anomaly of the heart characterised by the presence of a myocardial segment above a coronary artery, which results in a higher risk of cardiovascular events. In patients with prostate cancer treated with androgen receptor-targeted agents, a higher risk of cardiotoxicity was observed. CASE REPORT: An 88 years old man with metastatic castration-resistant prostate cancer in treatment with enzalutamide, denosumab, and triptorelin presented to our attention complaining dyspnoea and angina pectoris. MANAGEMENT AND OUTCOME: Blood examinations revealed normal Troponin I levels. Transthoracic echocardiography revealed no signs of acute myocardial ischaemia. The treadmill stress test revealed S-T tract under levelling in V4-V6 with a very slow resolution. Coronary angiography identified a myocardial bridge in the medium tract of the interventricular anterior artery. Due to these findings, ranolazine and simvastatin were started and, after multidisciplinary assessment, we decided to continue the treatment with enzalutamide. At the first follow-up visit echocardiography found out the cardiological reports stability and no therapy changes were performed. During follow-up visit cardiological revaluation showed reports stability and no therapy changes were performed. DISCUSSION: Due to the high prevalence of prostate cancer in elderly patients at high cardiovascular risk and the increasing use of androgen receptor-targeted agent, a multidisciplinary approach is highly recommended to weigh survival benefits on toxicities. This case report may support the use of androgen receptor-targeted agent in elderly patients with controlled cardiovascular diseases, a population that is often excluded from randomised trials.

Causes of deaths in long-term care and hospice care facilities during the first year of COVID-19 pandemic: a snapshot of Italy during 2020.

BACKGROUND: Older adults living in long-term care facilities (LTCF) have been severely affected by COVID-19. Hospice care (HC) facilities and palliative care are essential in treating patients dying from COVID-19. In Italy, little is known about the impact of COVID-19 on deaths in LTCF and the care provided in HC to COVID-19 patients. AIM: To assess overall and case-specific mortality in 2020 in LTC and HC facilities in comparison to the previous five years (2015-2019). METHODS: We performed a descriptive study using data derived from the Italian national "Cause of Death" registry-managed by the Italian National Institute of Statistics-on deaths occurred in LTC and HC facilities during 2020 and the period 2015-2019. RESULTS: Number of deaths significantly increased in 2020 compared with 2015-2019 in LTCF (83,062 deaths vs. 59,200) and slightly decreased in hospices (38,788 vs. 39,652). COVID-19 caused 12.5% of deaths in LTCF and only 2% in hospices. Other than COVID-19, in 2020, cancer accounted for 77% of all deaths that occurred in HC, while cardiovascular diseases (35.6%) and psychotic and behavioral disorders (10%) were the most common causes of death in LTCF. Overall, 22% of the excess mortality registered in Italy during 2020 is represented by the deaths that occurred in LTCF. DISCUSSION AND CONCLUSION: LTCF were disproportionally affected by COVID-19, while the response to the pandemic in HC was limited. These data can help plan strategies to limit the impact of future epidemics and to better understand residential care response to COVID-19 epidemic.

Recommendations of the International Society of Geriatric Oncology on skin cancer management in older patients.

INTRODUCTION: Non-melanoma skin cancer (NMSC) is becoming ever more prevalent among older adults. However, older adults with NMSC are often underrepresented in clinical trials and guidelines on effective management is still unclear. The International Society of Geriatric Oncology (SIOG) created a multi-disciplinary task force to explore the potential in developing practical guidelines for the treatment of older patients with basal cell carcinoma (BCC) and skin (cutaneous) squamous cell carcinoma (cSCC). MATERIALS AND METHODS: A systematic literature search to identify relevant and up-to-date literature on treatment of NMSC in older adults was conducted on various databases including MEDLINE, Embase, CINAHL, Cochrane, and PubMed. The resulting papers were discussed by an expert panel, leading to a consensus recommendation. RESULTS: A total of 154 articles were identified for the expert panel to utilise in generating consensus recommendations. A major focus on geriatric assessment and management options including surgery, radiotherapy, systemic therapy, clinical monitoring, and medical/medicophysical therapy were reviewed for recommendations. DISCUSSION: Patient age should not be the sole deciding factor in the management of patients with NMSC. Assessment from a multidisciplinary team (MDT) is crucial, and the decision-making process should consider the patient's lifestyle, needs, and expectations. A comprehensive geriatric assessment should also be considered. Patients should feel empowered to advocate for themselves and have their views considered a part of the MDT discussion.

Neutrophil-to-lymphocyte ratio predicts survival of patients with rectal cancer receiving neo-adjuvant chemoradiation followed by radical resection: a meta-analysis.

BACKGROUND: Neutrophil-to-lymphocyte ratio is suggested as a prognostic and predictive factor for patients with rectal cancer. The purpose of the current meta-analysis is to evaluate the relationship between neutrophil-lymphocyte ratio (NLR) and the outcome of patients, with rectal cancer receiving chemoradiation and surgery. METHODS: A systematic review on two databases and a selection of studies were done. Thereafter, two meta-analyses were performed, evaluating the relationship of baseline NLR with overall survival (OS) and disease-free survival (DFS). RESULTS: Thirty-one retrospective studies were selected. Twenty-six studies have documented a significant relationship of NLR to OS (HR 2.05, CI 1.66-2.53), whereas 23 studies have reported a weaker but significant relationship of NLR to DFS (HR 1.78, CI 1.49-2.12). Among the moderator variables, a possible effect for age and sex on the relationship of NLR with DFS is suggested. CONCLUSIONS: Baseline NLR >3 is a simple and reproducible prognostic factor, with a more consistent effect in the elderly. It could be a reliable variable to support clinicians in defining personalized treatment strategies, even though a standardization of the cutoff and a better characterization among microsatellite unstable rectal tumors are necessary.

Integration of art and technology in personalized radiation oncology care: Experiences, evidence, and perspectives.

Cancer diagnoses expose patients to traumatic stress, sudden changes in daily life, changes in the body and autonomy, with even long-term consequences, and in some cases, to come to terms with the end-of-life. Furthermore, rising survival rates underline that the need for interventions for emotional wellbeing is in growing demand by patients and survivors. Cancer patients frequently have compliance problems, difficulties during treatment, stress, or challenges in implementing healthy behaviors. This scenario was highlighted during the COVID-19 emergency. These issues often do not reach the clinical attention of dedicated professionals and could also become a source of stress or burnout for professionals. So, these consequences are evident on individual, interpersonal, and health system levels. Oncology services have increasingly sought to provide value-based health care, considering resources invested, with implications for service delivery and related financing mechanisms. Value-based health care can improve patient outcomes, often revealed by patient outcome measures while seeking balance with economical budgets. The paper aims to show the Gemelli Advanced Radiation Therapy (ART) experience of personalizing the patients' care pathway through interventions based on technologies and art, the personalized approach to cancer patients and their role as "co-stars" in treatment care. The paper describes the vision, experiences, and evidence that have guided clinical choices involving patients and professionals in a co-constructed therapeutic pathway. We will explore this approach by describing: the various initiatives already implemented and prospects, with particular attention to the economic sustainability of the paths proposed to patients; the several pathways of personalized care, both from the patient's and healthcare professional perspective, that put the person's experience at the Gemelli ART Center. The patient's satisfaction with the treatment and economic outcomes have been considered. The experiences and future perspectives described in the manuscript will focus on the value of people's experiences and patient satisfaction indicators, patients, staff, and the healthcare organization.

SUPeRO: A Multidimensional Approach to Prevent and Manage Oncological Frailty in a Radiation Oncology Unit.

Currently, the management of older cancer patients is directed by a personalized approach and, where possible, a tailor-made treatment. Based on our previous experiences and considering the opportunity of combining a geriatric department and a radiation-oncology department, we have developed a path that follows the patient from the beginning of the treatment, taking into account the complications/late toxicities and the survivors. This study aimed to evaluate the impact of remodeling and restructuring some oncology, radiotherapy, and geriatrics services based on the primary evidence for managing older cancer patients. In 2020, Gemelli ART underwent 60,319 radiation-oncology treatments, admitted 943 patients in the radiation-oncology and supportive care ward, and treated and followed 15,268 patients in clinics. The average length of stay of the admitted patients was reduced from 20.6 days to 13.2 days. In 2021, 1196 patients were assessed for frailty, 847 were admitted for toxicity, and 349 patients were evaluated within the geriatric oncology and supportive care outpatient clinic, and it was found that 59.2% were fit, 31.6% were vulnerable, and 9.2% were frail. This experience has shown a reduction in hospitalizations and the average hospital stay of patients in the case of side effects, a high toxicity to treatments, and the possibility of treating patients with a high level of complexity. This approach should represent the future target of geriatric oncology with the global management of older or complex patients with cancer.

Art and digital technologies to support resilience during the oncological journey: The Art4ART project.

Introduction: New digital technologies can become a tool for welcoming the patient through the artistic dimension. Cancer patients, in particular, need support that accompanies and supports them throughout their treatment. Materials and methods: The Art4ART project consist in the structural proposal to cancer patients of a web-based digital platform containing several forms of art as video-entertainments; a multimedia immersive room; an art-based welcoming of the patients with several original paintings; an environment with a peacefulness vertical garden; a reconceptualization of the chemotherapy-infusion seats. Data regarding patients' preference and choices will be stored and analysed also using artificial intelligence (AI) algorithm to measure and predict impact indicators regarding clinical outcomes (survival and toxicity), psychological indicators. Moreover, the same digital platform will contribute to a better organization of the activities. Discussion: Through the systematic acquisition of patient preferences and through integration with other clinical parameters, it will be possible to measure the clinical, psychological, organisational, and social impact of the newly implemented Art4ART project. The use of digital technology leads us to apply the reversal of viewpoint from therapeutic acts to patient-centred care.

Primary tumor resection in patients with unresectable colorectal cancer with synchronous metastases could improve the activity of poly-chemotherapy: A trial-level meta-analysis.

INTRODUCTION: Primary tumor resection (PTR) in patients with metastatic unresectable colorectal cancer is less and less used to prevent local complications. Although its therapeutic effect is debated, poor data are available about the activity of chemotherapy (CHT) after PTR. The study aims to evaluate trials that compared PTR followed by CHT vs. CHT alone. METHODS: After a literature search on two databases by predefined criteria, studies published from 2011 to 2021 were selected. All studies evaluating the progression-free survival (PFS) of patients receiving CHT after PTR or not were included in a meta-analysis. Finally, 18 possible moderating variables were extracted from each study and examined. RESULTS: Eleven trials reported a reduced risk of progression after first-line CHT among patients receiving PTR (HR 0.72, CI 0.66-0.79). The heterogeneity was moderate (Q = 17.52; p-value = 0.093) and the grade of inconsistence intermediate (I2 = 37.21%). Among moderating variables, female sex and low percentage of patients with liver metastases were related with a stronger effect size of PTR on PFS, whereas a longer OS and a trend to better PFS was evident after poly-chemotherapy regimens. CONCLUSION: PTR could improve the results of first-line CHT in patients with unresectable colorectal cancer with low tumor burden only in the subgroup receiving more aggressive chemotherapy.

Modern Management of Esophageal Cancer: Radio-Oncology in Neoadjuvancy, Adjuvancy and Palliation.

The modern management of esophageal cancer is crucially based on a multidisciplinary and multimodal approach. Radiotherapy is involved in neoadjuvant and adjuvant settings; moreover, it includes radical and palliative treatment intention (with a focus on the use of a stent and its potential integration with radiotherapy). In this review, the above-mentioned settings and approaches will be described. Referring to available international guidelines, the background evidence bases will be reviewed, and the ongoing, more relevant trials will be outlined. Target definitions and radiotherapy doses to administer will be mentioned. Peculiar applications such as brachytherapy (interventional radiation oncology), and data regarding innovative approaches including MRI-guided-RT and radiomic analysis will be reported. A focus on the avoidance of surgery for major clinical responses (particularly for SCC) is detailed.