Prediction of Response to Anti-Angiogenic Treatment for Advanced Colorectal Cancer Patients: From Biological Factors to Functional Imaging.

Colorectal cancer (CRC) is a leading tumor worldwide. In CRC, the angiogenic pathway plays a crucial role in cancer development and the process of metastasis. Thus, anti-angiogenic drugs represent a milestone for metastatic CRC (mCRC) treatment and lead to significant improvement of clinical outcomes. Nevertheless, not all patients respond to treatment and some develop resistance. Therefore, the identification of predictive factors able to predict response to angiogenesis pathway blockade is required in order to identify the best candidates to receive these agents. Unfortunately, no predictive biomarkers have been prospectively validated to date. Over the years, research has focused on biologic factors such as genetic polymorphisms, circulating biomarkers, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and microRNA. Moreover, research efforts have evaluated the potential correlation of molecular biomarkers with imaging techniques used for tumor assessment as well as the application of imaging tools in clinical practice. In addition to functional imaging, radiomics, a relatively newer technique, shows real promise in the setting of correlating molecular medicine to radiological phenotypes.

Immunotherapy and Cancer: The Multi-Omics Perspective.

Immunotherapies have revolutionized cancer treatment approaches. Because not all patients respond positively to immune therapeutic agents, it represents a challenge for scientists who strive to understand the mechanisms behind such resistance. In-depth exploration of tumor biology, using novel technologies such as omics science, can help decode the role of the tumor immune microenvironment (TIME) in producing a response to the immune blockade strategies. It can also help to identify biomarkers for patient stratification and personalized treatment. This review aims to explore these new models and highlight their possible pivotal role in changing clinical practice.

Understanding the User's Point of View: When the Doctor Gets Sick with Cancer and Seeks Help.

Background: When physicians confront a serious personal illness, they may discover that the transition to the "sick" role is challenging and not easy. We conducted a qualitative study in which a group of doctors with cancer (DP) was compared with a group of patients with cancer, not doctors (NDP) but with a degree of education, qualifications, and a professional role comparable to that of a doctor. Objectives: The main objective was to evaluate the effect of the diagnosis and the treatment of cancer on both the patient's personal and professional life. It was also designed to understand the effect that the experience of cancer may have on the subsequent clinical practice of DP. Methods: The eligibility criteria included diagnosis of tumors of different sites and at any stage of disease treated with local (surgery, radiotherapy) or systemic (chemotherapy, hormonal, target) therapies or a combination of both; patients actively working. A semi-structured interview was used to collect information about the patient's cancer experiences. In both groups, six main themes and ten subthemes were identified. Results: From July to November 2021, 59 patients were enrolled in the study. Among them, 29 were DP and 30 were NDP. The median age and gender were 55.9 years ± 9.3 SD (range 38-82 y), M/F ratio 12/17 for DP, and 56.3 years ± 8.9 SD (range 40-83 y), M/F ratio 11/19 for NDP, respectively. The main themes were: theme 1, practical aspects related to diagnosis: most of the DP did not encounter difficulties in performing the tests necessary to confirm the diagnosis of cancer, unlike what was observed in NDP. Theme 2, cancer diagnosis experience: Many DP and NDP felt prepared for their own cancer experience. Two-thirds of DP already knew their cancer prognosis from their previous background knowledge and one-third of NDP did not want to discuss the prognosis in depth with their referring oncologists for the fear of learning that their cancer had a poor prognosis. Theme 3, treatment experience: for many DP, having a professional background contributed to more active participation in care and also in the management of side effects of treatments. Most NDP were satisfied with the treatment received in the hospital and the relationship with the health professionals. Theme 4, changes in work: None of the patients from both the groups stopped working permanently or lost their job because of the disease. A higher number of DP and NDP reported a loss of interest in their job. Theme 5, changes in personal/family life and friendships: more than half of the patients in both groups developed a new perspective on their private lives. Theme 6, comfort from faith: most of the patients in both groups who followed a faith, found comfort in that faith. For DP only, we explored the theme of the change in the doctor/patient relationship. Important findings from our study included positive changes in the doctor's clinical practice including having a more empathic relationship with patients, greater consideration of the psychological impact of cancer, and greater attention to certain symptoms of cancer reported by patients. Conclusion: This study suggests the need to know the special needs of professional patients, in particular, related to the emotional difficulties, maintenance of privacy, and the need for support on their return to work. These results can help to foster improvements in current cancer care practices.

HE4 Tissue Expression as A Putative Prognostic Marker in Low-Risk/Low-Grade Endometrioid Endometrial Cancer: A Review.

Low-grade stage I endometrioid endometrial carcinomas should have an excellent prognosis, but a small subset of these cancers can relapse. The search for putative immunohistochemical prognostic markers for relapse in low-risk/low-grade endometrioid endometrial cancers remains open. Among the candidate molecules that may implicate the roles of immunohistochemical risk markers, we focused our attention on human epididymis protein 4 (HE4) after a review of the literature. Few authors have devoted themselves to this topic, and none have found a correlation between the tissue expression of HE4 and the molecular classification of endometrial cancer. Five different variants of HE4 mRNA and multiple protein isoforms of HE4 were identified many years ago, but current HE4 assays only measure the total HE4 expression and do not distinguish the different proteins encoded by different mRNA variants. It is important to have an approach to distinguish specific variants in the future.

How to improve metastatic pancreatic ductal adenocarcinoma patients' selection: Between clinical trials and the real-world.

As underlined in the minireview by Blomstrand et al, given the poor prognosis and the paucity of data on a therapeutic sequence in pancreatic ductal adenocarcinoma (PDAC), additional randomized controlled trials and real-world evidence studies addressing current and novel regimens are needed. The real-world outcomes of first-line chemotherapy regimens such as FOLFIRINOX and gemcitabine/nab-paclitaxel are thoroughly reviewed and seem to be largely generalizable in a real-world context. Regarding second-line chemotherapy, the key question about the optimal sequence of regimens remains uncertain. Precisely in this setting, it is therefore useful to encourage the implementation of clinical studies that may contribute to the scarcity of data available up to now. We report our experience with a small group of patients treated with second-line liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin. To improve the treatment of patients affected by PDAC, it is useful to identify subgroups of patients who may benefit from target treatments (e.g., BRCA mutant) and it is also important to focus on any prognostic factors that may affect the survival and treatment of these patients.

Alcohol Consumption Is a Modifiable Risk Factor for Breast Cancer: Are Women Aware of This Relationship?

AIMS: Despite alcohol consumption being a dose-dependent risk factor for breast cancer, a recent study conducted in the UK found <20% of women attending breast screening programmes were aware of this relationship and proposed proper information campaigns need to be conducted. We aimed to investigate the awareness of this relationship among a related sample of Italian women to evaluate whether similar information campaigns should also be conducted in Italy. METHODS: The questionnaire used by the UK study was translated into Italian, slightly modified for the Italian context, validated and submitted to a sample of Italian women. RESULTS: Overall 507 women were interviewed. Among them, 160 were classified as breast cancer screening attenders (SG), 44 as symptomatic breast clinic attenders (CAG) and 303 as non-screening group (NSG). Alcohol was correctly identified as a risk factor for breast cancer by 16.9, 11.4 and 14.9% of participants of SG, CAG and NSG, respectively without differences between the three groups. Despite the methodological differences, the rates of participants who correctly identified alcohol as a risk factor among women attending breast screening programmes were surprisingly similar between the study conducted in UK (15.7%) and the present study (16.9%). CONCLUSION: The results of the present study confirm the limited awareness of the relationship between alcohol consumption and risk of developing breast cancer among women and suggest the urgent need to conduct proper awareness-raising campaigns to counter this in the Italian female population.

Innate lymphoid cell recovery and occurrence of GvHD after hematopoietic stem cell transplantation.

Lymphocytes are essential for microbial immunity, tumor surveillance, and tissue homeostasis. However, the in vivo development and function of helper-like innate lymphoid cells (ILCs) in humans remain much less well understood than those of T, B, and NK cells. We monitored hematopoietic stem cell transplantation (HSCT) to determine the kinetics of ILC development in both children and adults. It was found that, unlike NK cells, helper-like ILCs recovered slowly, mirroring the pattern observed for T cells, with normalization achieved at 1 year. The type of graft and the proportion of CD34+ cells in the graft did not significantly affect ILC reconstitution. As HSCT is often complicated by acute or chronic graft-versus-host disease (GVHD), the potential role of ILC subsets in maintaining tissue integrity in these conditions was also analyzed. It was found that GVHD was associated with lower levels of activated and gut-homing NKp44+ ILCP, consistent with a non-redundant role of this ILC subset in preventing this life-threatening disorder in lymphopenic conditions.

PAX8 Positivity, Abnormal p53 Expression, and p16 Negativity in a Primary Endometrial Squamous Cell Carcinoma: A Case Report and Review of the Literature.

Primary endometrial squamous cell carcinoma (PESCC) is a rare entity. As the clinicopathologic features and the immunophenotype have not been completely defined yet, here we report our experience and review of the literature on this topic. A 73-yr-old nulliparous woman presented with pelvic pain and vaginal bleeding. Endometrial biopsy showed a carcinoma with squamous differentiation infiltrating the myometrium. Total hysterectomy with bilateral salpingo-oophorectomy and selective pelvic lymphadenectomy was performed. Definitive diagnosis was squamous carcinoma of the endometrium, with one lymph node metastasis (stage IIIC1). Immunohistochemistry evidenced immunoreactivity of the tumor cells for cytokeratin 5, p63, cytokeratin 7, PAX8, PTEN, and cyclin D1, aberrant p53 overexpression, and Ki-67 reactivity in ~70% of the tumor cells. Estrogen and progesterone receptor, PAX2, WT1, and p16 were negative. Our case was the first PAX8-positive PESCC in the literature, underlining the Mullerian system origin of this neoplasm. Abnormal p53 expression of this case confirmed its role in the pathogenesis of PESCC. Further studies on a large number of cases are needed to better understand the pathologic features and the immunophenotype of PESCC.

Circulating tumour DNA in gastrointestinal cancer in clinical practice: Just a dream or maybe not?

The evaluation of circulating tumor DNA (ctDNA) is increasingly integrated into the management of diagnosis and treatment of gastrointestinal cancer as it represents an innovative and minimally invasive biomarker that could allow us to reach clinical needs not met yet in randomized clinical trials. Recent research provided an interesting overview of the role of circulating tumor DNA in gastric, biliary, liver, pancreatic, and colorectal cancer. Data regarding upper gastrointestinal tumors are currently not practice changing. Tumor detection rates are low in the early stages, while in advanced stages ctDNA is useful for molecular tracking evaluation. Most of the evidence comes from colorectal cancer studies, where ctDNA was evaluated both in the early and advanced stages with the post-surgery minimal residual disease assessment and the response assessment, respectively. ctDNA qualifies as a promising tool in the era of precision medicine, with potential applications in the entire management of gastrointestinal cancer patients. Further evidence is needed to establish which setting may be influenced greatly by liquid biopsy in clinical practice.

The association between Major Depressive Disorder and premature death risk in hematologic and solid cancer: a longitudinal cohort study.

BACKGROUND: the aim was to verify the association between Major Depressive Disorders (MDD) and the risk of premature death in people with oncological diseases, and to collect evidence about the causality of a possible association from a longitudinal perspective. DESIGN AND METHODS: it is a cohort study lasting 9 months, involving people with solid or hematologic cancers. The assessment was conducted by an ad hoc form to collect socio-demographic and clinical-oncological data, the PHQ-9 to screen MDD (cut-off ≥10) and the SF-12 to evaluate HRQoL. Relative Risk (RR) of early death between MDD exposed and not-exposed and Kaplan-Meier survival were carried out. RESULTS: people exposed to MDD during the follow-up were 107/263 (40.7%). Among them, 36 deceased during the observation period. Overtime, having MDD and death' occurrence showed a strong association (RR=2.15; 95% CI (1.10-4.20); χ²=5.224, p=0.0022), confirmed by Kaplan-Meier survival analysis (χ²=4.357, p=0.037). Among people who died, there was not any association between MDD, age, gender, HRQoL, cancer stage and site. CONCLUSIONS: the study confirms the association between MDD and early death in people with cancer. The absence of any association between the onset of MDD and advanced stage of cancer may suggest that it could be due to the consequences of MDD in worsening the clinical conditions related to cancer. The findings point out the relevance of MDD' early detention among people with cancer.

The Quality of Life of People with Solid Cancer is Less Worse than Other Diseases with better Prognosis, Except in the Presence of Depression.

Background: Suffering from Solid Cancer (SC) may adversely impact the Health-related Quality of Life (H-QoL). The aims of this study are to measure the H-QoL in a sample of people suffering from SC and to clarify the role of the co-occurrence of depressive episodes. Results were compared with a healthy control group and with groups of other disorders. Methods: In 151 patients with SC (mean±sd age 63.1±11.5; female 54.3%), H-QoL was assessed by SF-12, depressive episodes were identified by PHQ-9. The attributable burden of SC in impairing H-QoL was calculated as the difference between SF-12 score of a community sex and age » matched healthy control group and that of the study sample. The attributable burden of SC was compared with other chronic diseases using specific diagnostic groups drawn from case-control studies that used the same database for selecting control samples. Results: H-QoL in people with SC was significantly worse than in the healthy control group (p<0.0001). The attributable burden in worsening the H-QoL due to SC was similar to those of severe chronic diseases, but lower than Multiple Sclerosis (p<0.0001) or Fibromyalgia (p<0.00001). Having a depressive episode was a strong determinant of decreasing H-QoL, regardless of the severity of cancer. Conclusion: The findings confirm a strong impact of SC but showed that H-QoL in SC was higher than in chronic diseases with better "quoad vitam" outcome. Since depression was a strong determinant, its prevention, early detection and therapy are the main objectives that must be reached in cancer patients.

An Overview of the International Literature on Health-Related Quality of Life, Mental Health and Psychosocial Issues in People with Cancer.

Background: Cancer is one of the most important leading causes of death worldwide. Early detection, screening and diagnosis have been demonstrated to significantly improve patients' survival rates and increase awareness of the benefit of prompt therapies and healthy lifestyles. In this context, Health-related Quality of Life (HRQoL) and several psychosocial difficulties are of relevance as prognostic factors for the trajectory of the diseases of people living with cancer. Methods: This Special Issue aims to present a set of systematic reviews and research studies focusing on several psychosocial aspects in people suffering from hematologic and solid cancer. Results: Three systematic reviews regard HRQoL, the quality of patient-physician communication, depression and other stress-related difficulties, respectively. One review pointed out the difficulties in diagnosing depression in the elderly with solid cancer; another one regards the risk of cancer in severe mental illnesses, such as schizophrenia, bipolar disorders, and severe depressive disorders. One additional review regards HRQoL in people with cancer in the present era of COVID-19 pandemic. Furthermore, some research studies pointed out the usefulness of a validated instrument to assess satisfaction with care in the oncology field, as well as of the self-reinforcing feedback loop to improve fatigue, insomnia and depression in people with cancer. Other two research studies evaluate, respectively, the attributable burden in worsening HRQoL in people suffering both from cancer and depression and the Type D personality as a risk factor for stress-related difficulties in women with breast cancer. Conclusion: This Special Issue is a contribution to enhance future research mainly about such interventions useful to assess and improve HRQoL and overall well-being in people with cancer.

The Difficult Task of Diagnosing Depression in Elderly People with Cancer: A Systematic Review.

Background: Depression is a common psychiatric problem in the elderly and oncology patients. In elderly people with cancer, depression has a peculiar phenomenology. It has a significant impact on the quality of life. Moreover, it is associated with poor adherence to treatments, increased risk of suicide, and mortality. Nevertheless, the topic of depression in elderly people with cancer remains unexplored. Objective: The main goal of this article is to review the literature from the past 20 years on the relationships between depression, cancer, and aging. Methods: The methods followed the Prisma model for eligibility of studies. The articles in which the keywords "depression", "cancer", " elderly, aging, or geriatric" were present, either in the text or in the abstract, were selected. 8.056 articles, by matching the keywords "depression and elderly and cancer," were identified. Only 532 papers met the eligibility criteria of search limits and selection process. Out of 532 papers, 467 were considered irrelevant, leaving 65 relevant studies. Out of 65 suitable studies, 39 (60.0%) met our quality criteria and were included. Results: The risk factors associated with depression in elderly people with cancer can be divided into 4 groups: 1) tumor-related; 2) anticancer treatment-related; 3) patients-related; 4) number and type of comorbidity. The main obstacles in diagnosing depression in elderly patients with cancer are the overlap of the symptoms of cancer and side effects of treatment with the symptoms of depression but also the different ways of reporting depressive symptoms of elderly people and the different clinical types of depression. There is a lack of data regarding validated scales to assess depression in geriatric patients with cancer. Any mental illness, specifically co-occurring anxiety and depression, increases the risk of diagnosis delay and anticancer treatment adherence. Cancer and the diagnosis of mental disorders prior to cancer diagnosis correlate with an increased risk for suicide. A non-pharmacological therapeutic approach, pharmacological treatment and/or a combination of both can be used to treat elderly patients with cancer, but a detailed analysis of comorbidities and the assessment of polypharmacy is mandatory in order to avoid potential side-effects and interactions between antidepressants and the other drugs taken by the patients. Conclusion: Future research should be conducted with the aim of developing a modified and adapted assessment method for the diagnosis and treatment of depression in elderly people with cancer in order to improve their clinical outcomes and quality of life.

Health Related Quality of Life in Patients with Onco-hematological Diseases.

BACKGROUND: HRQoL is generally conceptualized as a broad multidimensional construct that refers to patients' perceptions of the impact of disease and its treatment on their physical, psychological, and social functioning and well-being. Little is known in patients with onco-hematological cancer in comparison with the general population and other chronic diseases. OBJECTIVE: We assessed HRQoL in patients diagnosed with haematological cancers in comparison with the general population and other chronic diseases. METHODS: The questionnaire Short Form (SF)-12 was administered to 62 patients with onco-hematological disease and results were compared with 702 controls (184 healthy people, 37 Major Depression, 201 Multiple Sclerosis; 23 Wilson disease; 46 Carotidal Atherosclerosis; 60 Celiac disease; 151 solid tumours). RESULTS: HRQoL in patients diagnosed with a haematological cancer was significantly worse in comparison with the general population (F= 43.853, p <0.00001) but similar when compared with solid tumour and other chronic diseases such as Major Depression and Carotid Atherosclerosis. In addition, HRQoL in patients diagnosed with a haematological cancer was significantly higher than that due to Celiac disease (p <0.00001) and Wilson's disease (p= 0.02), and lower than that due to Multiple Sclerosis (p= 0.032). CONCLUSION: This study confirmed that haematological cancers negatively affects overall HRQoL. The results showed an impact of haematological cancers on HRQoL that is similar to what found in patients with solid tumors, Major Depression and Carotid Atherosclerosis. Current successful therapeutic strategy achieved in the treatment of haematological cancers not only positively impact on survival rate but also could improve the overall HRQoL.

Molecular-Biology-Driven Treatment for Metastatic Colorectal Cancer.

BACKGROUND: Metastatic CRC (mCRC) is a molecular heterogeneous disease. The aim of this review is to give an overview of molecular-driven treatment of mCRC patients. METHODS: A review of clinical trials, retrospective studies and case reports was performed regarding molecular biomarkers with therapeutic implications. RESULTS: RAS wild-type status was confirmed as being crucial for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies and for rechallenge strategy. Antiangiogenic therapies improve survival in first- and second-line settings, irrespective of RAS status, while tyrosine kinase inhibitors (TKIs) remain promising in refractory mCRC. Promising results emerged from anti-HER2 drugs trials in HER2-positive mCRC. Target inhibitors were successful for BRAFV600E mutant mCRC patients, while immunotherapy was successful for microsatellite instability-high/defective mismatch repair (MSI-H/dMMR) or DNA polymerase epsilon catalytic subunit (POLE-1) mutant patients. Data are still lacking on NTRK, RET, MGMT, and TGF-ß, which require further research. CONCLUSION: Several molecular biomarkers have been identified for the tailored treatment of mCRC patients and multiple efforts are currently ongoing to increase the therapeutic options. In the era of precision medicine, molecular-biology-driven treatment is the key to impro patient selection and patient outcomes. Further research and large phase III trials are required to ameliorate the therapeutic management of these patients.

Number and function of circulatory helper innate lymphoid cells are unaffected by immunosuppressive drugs used in solid organ recipients - a single centre cohort study.

In transplanted intestines, depletion of T cells together with long-term persistence of ILC is observed, suggesting ILC insensitivity to immunosuppressive drugs. To further analyze helper ILC (hILC) apparent resistance to therapy, cytotoxic ILC (NK cells), hILC subsets (ILC1, ILC2, and ILC precursors (ILCP)), and their signature cytokines (IFNγ, IL4 + IL13, and IL22) were analyzed in peripheral blood of kidney and liver transplant recipients. Early after transplantation (posTx), transplanted patients showed significantly lower Lin + and NK cells, whereas total hILC, ILC1, ILC2, and ILCP numbers were similar in patients and controls. Between paired pre- and posTx samples, Lin + cell and NK cell counts significantly decreased, whereas all three hILC counts and their cytokine production remained similar. ILC1, ILC2, and ILCP numbers were also similar in patients under thymoglobulin or basiliximab (BAS), patients without induction (only maintenance therapy) and controls. hILC showed lower TMG binding comparing to Lin + cells, reduced expression of CD25 (BAS target), and diminished calcineurin activity with undetectable calcineurin and FKBP12 (tacrolimus target). hILC counts were not related to delayed graft function or biopsy-proven acute rejection. Thus, hILC remain stable early after transplantation and seem unaffected by immunosuppressors, which may be related to reduced targets expression and low calcineurin activity.

Sense of coherence and physical health-related quality of life in Italian chronic patients: the mediating role of the mental component.

OBJECTIVE: To examine the relationship between sense of coherence (SOC) and physical health-related quality of life in patients with chronic illnesses by focusing on the mediating role of the mental component of quality of life. DESIGN: Cross-sectional survey design. SETTING: Secondary care; three departments of an Italian university hospital. METHODS: The participants (n=209) in the study were adult (≥18 years) outpatients with a chronic pathology (eg, diabetes, thyroid disorders or cancer) at any phase in the care trajectory (eg, pre-treatment, undergoing treatment, follow-up care). They agreed to participate in the study after providing their informed consent. Data were collected using a structured self-reporting questionnaire. Data analysis was carried out using SPSS, and mediation analysis was performed via PROCESS macro. RESULTS: The SOC score of the study sample was equivalent to that of the general population (mean difference=-2.50, 95% CI -4.57 to 0.00). Correlation analysis showed that SOC was mainly correlated to the mental component (MCS) (r=0.51, p<0.01) of quality of life and then to the physical component (PCS) (r=0.35, p<0.01). Mediation analysis showed that SOC was directly related to MCS (p<0.001, 95% CI 0.62 to 0.99) but not to PCS (p=0.42, 95% CI -0.27 to 0.12). In turn, MCS was directly related to PCS (p<0.001, 95% CI 0.76 to 1.01). The indirect effect of SOC on PCS through MCS was significant (0.71, p<0.001, bootstrap 95% CI 0.54 to 0.91), thus supporting the mediating role of the mental component of quality of life. CONCLUSION: The indirect effect suggests that SOC is a marker of quality of life, especially of the mental component. The findings show that SOC is a psychological process that impacts patients' mental health status, which in turn affects physical health. Better knowledge of a person's SOC and how it affects his/her quality of life may help to plan tailoring interventions to strengthen SOC and improve health-related quality of life.

Regorafenib-induced hypothyroidism and cancer-related fatigue: is there a potential link?

OBJECTIVE: Thyroid dysfunction has been reported during Regorafenib (Reg) administration, but no detailed study is presently available. DESIGN: Prospective, observational cohort study. Patients with documented metastatic colorectal cancer and progression of disease during or within 3 months after the last standard therapy, with no evidence and history of previous thyroid disease were enrolled. METHODS: Twenty-five consecutive patients were evaluated before and 8-50 weeks after initiating Reg therapy by monthly clinical, ultrasound and laboratory (thyrotropin (TSH), free thyroxine (fT4), antithyroglobulin (TgAb) and antithyroid peroxidase (TPOAb)) evaluation. RESULTS: Thirteen/25 patients (52%) became hypothyroid (TSH: 12.5 ± 4.01 IU/L, range: 4.6-22.0) within 5 months of therapy. TPOAb became detectable (99-155 IU/mL) in 2/25 (8%) patients. Thyroid volume progressively decreased (from 8.6 ± 2.2 mL to 4.9 ± 2.4 mL after 5 months of Reg therapy, P < 0.0001). The progression-free survival (PFS) was longer in patients developing hypothyroidism (43 weeks) than in those remaining euthyroid (17 weeks, P < 0.01). Fatigue (the most common general serious Reg adverse event) was associated with hypothyroidism severity and reversed after levothyroxine therapy (L-T4). CONCLUSIONS: Reg rapidly causes hypothyroidism in about 50% of patients and in a minority of them also triggers thyroid autoimmunity. Reg-induced hypothyroidism was strictly related to fatigue, easily reversed by L-T4 administration and associated to longer survival. These results suggest that prompt recognition of hypothyroidism in patients with severe fatigue may prevent unnecessary Reg dose reduction or withdrawal.

Position paper of the Italian Association of Medical Oncology on early palliative care in oncology practice (Simultaneous Care).

One of the priorities of personalized medicine regards the role of early integration of palliative care with cancer-directed treatments, called simultaneous care. This article, written by the Italian Association of Medical Oncology (AIOM) Simultaneous and Continuous Care Task Force, represents the position of Italian medical oncologists about simultaneous care, and is the result of a 2-step project: a Web-based survey among medical oncologists and a consensus conference. We present the opinion of more than 600 oncologists who helped formulate these recommendations. This document covers 4 main aspects of simultaneous care: 1) ethical, cultural, and relational aspects of cancer and implications for patient communication; 2) training of medical oncologists in palliative medicine; 3) research on the integration between cancer treatments and palliative care; and 4) organizational and management models for the realization of simultaneous care. The resulting recommendations highlight the role of skills and competence in palliative care along with implementation of adequate organizational models to accomplish simultaneous care, which is considered a high priority of AIOM in order to grant the best quality of life for cancer patients and their families.