Perceptions of Death Among Patients with Advanced Cancer Receiving Early Palliative Care and Their Caregivers: Results from a Mixed-Method Analysis.

BACKGROUND: Oncologists are often concerned that talking about death with patients may hinder their relationship. However, the views of death held by patients have not been thoroughly investigated. This study aimed to describe the perception of death among patients with advanced cancer receiving early palliative care (EPC) and their caregivers. MATERIAL AND METHODS: Qualitative and quantitative analyses were performed on 2 databases: (a) transcripts of open-ended questionnaires administered to 130 cancer patients receiving EPC with a mean age of 68.4 years and to 115 primary caregivers of patients on EPC with a mean age of 56.8; (b) texts collected from an Italian forum, containing instances of web-mediated interactions between patients and their caregivers. RESULTS: Quantitative analysis shows that: (a) patients and caregivers are not afraid of speaking about death; (b) patients and caregivers on EPC use the word "death" significantly more than patients on standard oncology care (SOC) and their caregivers (P < .0001). For both participants on EPC and SOC, the adjectives and verbs associated with the word "death" have positive connotations; however, these associations are significantly more frequent for participants on EPC (verbs, Ps < .0001; adjectives, Ps < .003). Qualitative analysis reveals that these positive connotations refer to an actual, positive experience of the end of life in the EPC group and a wish or a negated event in the SOC group. CONCLUSIONS: EPC interventions, along with proper physician-patient communication, may be associated with an increased acceptance of death in patients with advanced cancer and their caregivers.

Perceptions of Hope Among Bereaved Caregivers of Cancer Patients Who Received Early Palliative Care: A Content and Lexicographic Analysis.

BACKGROUND: Oncologists' fear of taking away hope from patients when proposing early palliative care (EPC) is a barrier to the implementation of this model. This study explores hope perceptions among bereaved caregivers of onco-hematologic patients who received EPC. MATERIALS AND METHODS: Open-ended questionnaires were administered to 36 primary caregivers of patients who received EPC (26 solid and 10 hematologic cancer patients; mean age: 51.4 years, range age: 20-74), at 2 cancer centers, 2 months to 3 years after a patient death. Definitions of hope in the caregivers' narratives were analyzed through a directed approach to content analysis. Results were complemented with automated lexicographic analysis. RESULTS: Caregivers perceived hope mainly as resilience and as expectations based on what they were told about the patients' clinical conditions. Their hope was bolstered by trusting relationships with the healthcare teams. EPC interventions were recalled as the major support for hope, both during the illness and after the death of the patient. The automated quantitative lexical analysis provided deeper insights into the links between hope, truth, and trust. CONCLUSIONS: Our findings suggest that telling the truth about an incurable onco-hematologic disease and beginning EPC might be the combination of factors triggering hope in the setting of incurable cancer.

Prognostic Role of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma: A Large, Multicenter, Prospective Trial.

BACKGROUND: Circulating tumor cells (CTCs) correlate with adverse prognosis in patients with breast, colorectal, lung, and prostate cancer. Little data are available for renal cell carcinoma (RCC). MATERIALS AND METHODS: We designed a multicenter prospective observational study to assess the correlation between CTC counts and progression-free survival (PFS) in patients with metastatic RCC treated with an antiangiogenic tyrosine kinase inhibitor as a first-line regimen; overall survival (OS) and response were secondary objectives. CTC counts were enumerated by the CellSearch system at four time points: day 0 of treatment, day 28, day 56 and then at progression, or at 12 months in the absence of progression. RESULTS: One hundred ninety-five eligible patients with a median age of 69 years were treated with sunitinib (77.5%) or pazopanib (21%). At baseline, 46.7% of patients had one or more CTCs per milliliter (range, 1 to 263). Thirty patients had at least three CTCs, with a median PFS of 5.8 versus 15 months in the remaining patients (p = .002; hazard ratio [HR], 1.99), independently of the International Metastatic RCC Database Consortium score at multivariate analysis (HR, 1.91; 95% confidence interval [CI], 1.16-3.14). Patients with at least three CTCs had a shorter estimated OS of 13.8 months versus 52.8 months in those with fewer than three CTCs (p = .003; HR, 1.99; multivariate analysis HR, 1.67; 95% CI, 0.95-2.93). Baseline CTC counts did not correlate with response; neither did having CTC sequencing counts greater than or equal to one, two, three, four, or five. CONCLUSION: We provide prospective evidence that the presence of three or more CTCs at baseline is associated with a significantly shorter PFS and OS in patients with metastatic RCC. IMPLICATIONS FOR PRACTICE: This prospective study evaluated whether the presence of circulating tumor cells (CTCs) in the peripheral blood correlates with activity of first-line tyrosine kinase inhibitors in metastatic renal cell carcinoma (RCC). This study demonstrated that almost half of patients with metastatic RCC have at least one CTC in their blood and that those patients with at least three CTCs are at increased risk of early progressive disease and early death due to RCC. Studies incorporating CTC counts in the prognostic algorithms of metastatic RCC are warranted.

Changes in Cancer Patients' and Caregivers' Disease Perceptions While Receiving Early Palliative Care: A Qualitative and Quantitative Analysis.

BACKGROUND: Little is known about the underlying mechanisms through which early palliative care (EPC) improves multiple outcomes in patients with cancer and their caregivers. The aim of this study was to qualitatively and quantitatively analyze patients' and caregivers' thoughts and emotional and cognitive perceptions about the disease prior to and during the EPC intervention, and in the end of life, following the exposure to EPC. MATERIALS AND METHODS: Seventy-seven patients with advanced cancer and 48 caregivers from two cancer centers participated in semistructured interviews. Their reports were qualitatively and quantitatively analyzed by the means of the grounded theory and a text-analysis program. RESULTS: Participants reported their past as overwhelmed by unmanaged symptoms, with detrimental physical and psychosocial consequences. The EPC intervention allowed a prompt resolution of symptoms and of their consequences and empowerment, an appreciation of its multidimensional approach, its focus on the person and its environment, and the need for EPC for oncologic populations. Patients reported that conversations with the EPC team increased their acceptance of end of life and their expectation of a painless future. Quantitative analysis revealed higher use of Negative Affects (p < .001) and Biological Processes words (p < .001) when discussing the past; Agency words when discussing the present (p < .001); Positive Affects (p < .001), Optimism (p = .002), and Insight Thinking words (p < .001) when discussing the present and the future; and Anxiety (p = .002) and Sadness words (p = .003) when discussing the future. CONCLUSION: Overall, participants perceived EPC to be beneficial. Our findings suggest that emotional and cognitive processes centered on communication underlie the benefits experienced by participants on EPC. IMPLICATIONS FOR PRACTICE: By qualitative and quantitative analyses of the emotional and cognitive perceptions of cancer patients and their caregivers about their experiences before and during EPC interventions, this study may help physicians/nurses to focus on the disease perception by patients/caregivers and the benefits of EPC, as a standard practice. The analysis of words used by patients/caregivers provides a proxy for their psychological condition and support in tailoring an EPC intervention, based on individual needs. This study highlights that the relationship of the triad EPC team/patients/caregivers may rise as a therapeutic tool, allowing increasing awareness and progressive acceptance of the idea of death.

Activity and safety of metronomic cyclophosphamide in the modern era of metastatic castration-resistant prostate cancer.

AIM: To evaluate activity of metronomic cyclophosphamide (mCTX) in heavily pretreated metastatic castration-resistant prostate cancer (mCRPC) patients. PATIENTS & METHODS: We retrospectively evaluated a consecutive series of 74 mCRPC patients treated with at least one new agent after docetaxel failure, who received once-daily oral mCTX treatment at a fixed dose of 50 mg. RESULTS: The treatment was well tolerated. Sixteen percent of the patients experienced a major biochemical response. Median progression-free survival was 4.0 months, and median overall survival was 8.1 months. CONCLUSIONS: In the modern context of mCRPC, mCTX may represent a valuable and inexpensive alternative to new agents, which have shown similar activity in heavily pretreated patients.

Correction to: Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide? A PERNO prospective study.

The members of the PERNO Study Group were not individually captured in the metadata of the original publication. They are included in the metadata of this publication.

Negative prognostic factors and resulting clinical outcome in patients with metastatic renal cell carcinoma included in the Italian nivolumab-expanded access program.

AIM: We report the outcomes observed with nivolumab in metastatic renal cell carcinoma patients with poor prognostic features enrolled in the Italian expanded access program. PATIENTS & METHODS: Nivolumab was available for patients who relapsed after at least one prior systemic treatment in the advanced or metastatic setting. RESULTS: Of 389 patients, 32 (8%) had brain metastasis, 129 (33%) had liver and 193 (50%) had bone metastasis. These subpopulations achieved a disease control rate of 53, 45 and 47%, respectively. Fifty-one patients had G4 tumor, and they showed 23% objective response rate. The safety profile of the subgroups was in line with the expanded access program population. No new safety signals were reported. CONCLUSION: Patients with poor prognostic features may derive relevant benefits from nivolumab.

Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide? A PERNO prospective study.

The role of temozolomide concurrent with and adjuvant to radiotherapy (RT/TMZ) in elderly patients with glioblastoma (GBM) remains unclear. We evaluated the outcome of patients >70 years in the context of the Project of Emilia-Romagna Region in Neuro-Oncology (PERNO), the first Italian prospective observational population-based study in neuro-oncology. For this analysis the criteria for selecting patients enrolled in the PERNO study were: age >70 years; PS 0-3; histologically confirmed GBM; postoperative radiotherapy (RT) after surgery with or without concomitant temozolomide (TMZ) or postsurgical TMZ alone. Between January 2009 and December 2010, 76 GBM elderly patients were identified in the prospective PERNO study. Twenty-three patients did not receive any treatment after surgery, and 53 patients received postsurgical treatments (25 patients received RT alone and 28 patients RT/TMZ). Median survival was 11.1 months (95 % CI 8.8-13.5), adding temozolomide concomitant and adjuvant to radiotherapy it was 11.6 months (95 % CI 8.6-14.6), and 9.3 months (95 % CI 8.1-10.6) in patients treated with RT alone (P = 0.164). However, patients with MGMT methylated treated with RT/TMZ obtained a better survival (17.2 months, 95 % CI 11.5-22.9) (P = 0.042). No difference in terms of survival were observed if patients with MGMT unmethylated tumor received RT alone, or RT/TMZ or, in MGMT methylated tumor, if patients received radiotherapy alone. In elderly patients RT/TMZ represent a widely used approach but it is effective with methylated MGMT tumors only.

Clinical outcomes in octogenarians treated with docetaxel as first-line chemotherapy for castration-resistant prostate cancer.

AIM: To assess clinical outcomes in octogenarians treated with docetaxel (DOC) for metastatic castration-resistant prostate cancer. PATIENTS & METHODS: The multicenter retrospective study was based on a review of the pre- and post-DOC clinical history, DOC treatment and outcomes. RESULTS: We reviewed the records of 123 patients (median age: 82 years) who received DOC every 3 weeks or weekly, without significant grade 3-4 toxicities. Median progression-free survival was 7 months; median overall survival from the start of DOC was 20 months, but post-progression treatments significantly prolonged overall survival. CONCLUSION: The findings of this study suggest that toxicity is acceptable, survival is independent of patient's age and survival can be significantly prolonged by the use of new agents.

Positive Psychological Well-Being in Early Palliative Care: A Narrative Review of the Roles of Hope, Gratitude, and Death Acceptance.

In the advanced cancer setting, low psychological functioning is a common symptom and its deleterious impact on health outcomes is well established. Yet, the beneficial role of positive psychological well-being (PPWB) on several clinical conditions has been demonstrated. Early palliative care (EPC) is a recent value-based model consisting of the early integration of palliative care into standard care for solid tumors and hematologic malignancies. While the late palliative care primary offers short-term interventions, predominantly pharmacological in nature and limited to physical symptom reduction, EPC has the potential to act over a longer term, enabling specific interventions aimed at promoting PPWB. This narrative review examines nine English studies retrieved from MEDLINE/PubMed, published up to October 2023, focusing on EPC and three dimensions of PPWB: hope, gratitude, and death acceptance. These dimensions consistently emerge in our clinical experience within the EPC setting for advanced cancer patients and appear to contribute to its clinical efficacy. The choice of a narrative review reflects the novelty of the topic, the limited existing research, and the need to incorporate a variety of methodological approaches for a comprehensive exploration.

Assessing the effectiveness and safety of lenvatinib and everolimus in advanced renal cell carcinoma: insights from the RELIEVE study's analysis of heavily pretreated patients.

Background: The treatment of heavily pretreated patients with metastatic renal cell carcinoma (mRCC) represents an unmet medical need and is still challenging. Objectives: The primary objective was to assess the effectiveness of the lenvatinib plus everolimus combination and the secondary objective was the toxicity profile of this combination. Design: We conducted a longitudinal retrospective study examining mRCC patients pre-treated with one or more lines of therapy among different cancer centers in Italy. Methods: The study included patients who received the combination of lenvatinib plus everolimus as either a second-line treatment or beyond. We assessed progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), response rate (RR), and toxicity profile. In addition, we explored the potential relationship between treatment effectiveness and clinical and laboratory parameters. Results: In all, 33 patients were assessed, the median age was 60 years, 57% had an Eastern Cooperative Oncology Group performance status of 1-2 and. 63% received ⩾ 3 prior lines of therapy. 62% were 'intermediate risk' according to the International Metastatic Renal Cell Carcinoma Database Consortium and 30% were 'poor risk'. The RR was 42% (no complete response), 18% stable disease. Median OS was 11.2 months (95% CI 6.8-19.9), median PFS was 6.7 months (95% CI 0.6-30.8), and median TTF was 6.7 months (95% CI 4.8-16.6). A shorter OS was significantly associated with lymph node metastases (p = 0.043, 95% CI), neutrophils/ lymphocytes ratio (NLR) ⩾ 3 (p = 0.007), hemoglobin/red cell distribution width ratio cutoff value <0.7 was significant (p = 0.03) while a shorter PFS was associated with lung (p = 0.048) and brain metastases (p = 0.023). The most frequent G1 toxicity was diarrhea (24%), G2 was fatigue (30%), and hypertension and skin toxicity (6%) for G3. Conclusion: Our findings suggest a clinically relevant effectiveness of lenvatinib plus everolimus combination with an acceptable toxicity profile for heavily pretreated patients with mRCC.

Stigma of Palliative Care among Patients with Advanced Cancer and Their Caregivers on Early Palliative Care.

The early referral to palliative care (PC) represents a successful value-based model with proven benefits regarding the quality of life and clinical outcomes for advanced cancer patients and their caregivers. Yet, its provision remains typically confined to the last weeks of life as per the historical, late PC model. The stigma according to which PC represents end-of-life care has been identified as the root of the problem. To explore the presence and effects of the stigma in a clinical context, we surveyed 78 patients and 110 caregivers (mean age: 71.7 and 60.7, respectively) on early PC to study what their perception of PC was before their direct experience. The responses were analyzed through a qualitative descriptive approach. The participants explicitly mentioned a lack of knowledge about PC (53% of the sample), which they identified also among physicians and the population (13%); an identification of PC with the late PC model (53%); and a detrimental reaction to the proposal of an early PC referral (83%). However, the participants explicitly mentioned that a direct experience of early PC allowed for an acquired awareness of early PC meaning and benefits (52%), as well as a comprehension of its differences with late PC (34%); the regret for the delayed referral (8%); the perception of the word "palliative" as a barrier (21%); and the belief that early PC should be part of the cancer routine practice (25%). A comprehensive multi-level intervention is necessary for a widespread understanding of the essence of anticipated PC.

Impact of influenza vaccination on survival of patients with advanced cancer receiving immune checkpoint inhibitors (INVIDIa-2): final results of the multicentre, prospective, observational study.

Background: The prospective multicentre observational INVIDIa-2 study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving immune checkpoint inhibitors (ICI). In this secondary analysis of the original trial, we aimed to assess the outcomes of patients to immunotherapy based on vaccine administration. Methods: The original study enrolled patients with advanced solid tumours receiving ICI at 82 Italian Oncology Units from Oct 1, 2019, to Jan 31, 2020. The trial's primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020, the results of which were reported previously. Secondary endpoints (data cut-off Jan 31, 2022) included the outcomes of patients to immunotherapy based on vaccine administration, for which the final results are reported herein. A propensity score matching by age, sex, performance status, primary tumour site, comorbidities, and smoking habits was planned for the present analysis. Only patients with available data for these variables were included. The outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease-control rate (DCR). Findings: The original study population consisted of 1188 evaluable patients. After a propensity score matching, 1004 patients were considered (502 vaccinated and 502 unvaccinated), and 986 of them were evaluable for overall survival (OS). At the median follow-up of 20 months, the influenza vaccination demonstrated a favourable impact on the outcome receiving ICI in terms of median OS [27.0 months (CI 19.5-34.6) in vaccinated vs. 20.9 months (16.6-25.2) in unvaccinated, p = 0.003], median progression-free survival [12.5 months (CI 10.4-14.6) vs. 9.6 months (CI 7.9-11.4), p = 0.049], and disease-control rate (74.7% vs. 66.5%, p = 0.005). The multivariable analyses confirmed the favourable impact of influenza vaccination in terms of OS (HR 0.75, 95% C.I. 0.62-0.92; p = 0.005) and DCR (OR 1.47, 95% C.I. 1.11-1.96; p = 0.007). Interpretation: The INVIDIa-2 study results suggest a favourable immunological impact of influenza vaccination on the outcome of cancer patients receiving ICI immunotherapy, further encouraging the vaccine recommendation in this population and supporting translational investigations about the possible synergy between antiviral and antitumour immunity. Funding: The Federation of Italian Cooperative Oncology Groups (FICOG), Roche S.p.A., and Seqirus.

Nivolumab in Combination with Stereotactic Body Radiotherapy in Pretreated Patients with Metastatic Renal Cell Carcinoma. Results of the Phase II NIVES Study.

BACKGROUND: Nivolumab showed an overall survival (OS) benefit in pretreated metastatic renal cell carcinoma (mRCC). The role of stereotactic body radiotherapy (SBRT) in mRCC remains to be defined. OBJECTIVE: Our aim was to evaluate the efficacy and safety of SBRT in combination with nivolumab in second- and third-line mRCC patients. DESIGN, SETTING, AND PARTICIPANTS: The NIVES study was a phase II, single-arm, multicenter trial in patients with mRCC with measurable metastatic sites who progressed after antiangiogenic therapy, of whom at least one was suitable for SBRT. INTERVENTION: The patients received SBRT to a lesion at a dose of 10 Gy in three fractions for 7 d from the first infusion of nivolumab. Nivolumab was given at an initial dose of 240 mg every 14 d for 6 mo and then 480 mg q4-weekly in responding patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We hypothesized that nivolumab plus SBRT improves the objective response rate (ORR) compared with nivolumab alone from 25% (derived from historical controls) to 40%. Secondary endpoints were progression-free survival (PFS), OS, disease control rate (DCR) of irradiated and nonirradiated metastases, and safety. RESULTS AND LIMITATIONS: Sixty-nine patients were enrolled from July 2017 to March 2019. The ORR was 17% and the DCR was 55%. The median PFS was 5.6 mo (95% confidence interval [CI], 2.9-7.1) and median OS 20 mo (95% CI, 17-not reached). After 1.5 yr of follow-up, 23 patients died. The median time to treatment response was 2.8 mo and median duration of response was 14 mo. No new safety concerns arose. CONCLUSIONS: We did not find sufficient evidence to suggest that nivolumab in combination with SBRT provides an added benefit in pretreated mRCC patients; it should however be evaluated in patients with oligometastatic or oligoprogressive disease. PATIENT SUMMARY: Nivolumab in combination with stereotactic body radiotherapy does not provide evidence of increased outcomes in metastatic renal cell carcinoma patients. However this approach was safe and showed a good response of the irradiated lesions.

Cabozantinib beyond progression improves survival in advanced renal cell carcinoma patients: the CABEYOND study (Meet-URO 21).

BACKGROUND: Cabozantinib improves survival in metastatic renal cell carcinoma (mRCC) after prior antiangiogenics. The best treatment at disease progression (PD) is unknown. Being also a AXL/MET inhibitor, involved in acquired resistance, we hypothesized a prolonged tumor growth control in patients continuing cabozantinib despite PD. RESEARCH DESIGN AND METHODS: This retrospective multicenter study enrolled patients receiving cabozantinib after the first line between 2014 and 2020. We compared patients maintaining cabozantinib after first PD due to clinical benefit and good tolerability with those who changed therapy. The postprogression survival (PPS) of both was our primary endpoint. RESULTS: We analyzed 89 patients: 45 received cabozantinib beyond PD and 44 switched therapy. 40.4%, 31.5%, and 28.1% of patients received 1, 2, or >2 prior treatment, respectively. 84.3% were intermediate-poor International Metastatic Renal Cell Carcinoma Database risk. Patients continuing cabozantinib showed a higher response rate to cabozantinib before PD (46.7% vs 25%, p = 0.03) and were more heavily pretreated. Continuing cabozantinib showed a significantly longer PPS compared with switching therapy (median PPS 16.9 vs 13.2 months, HR 0.66, 95%CI 0.48-0.92, p = 0.011). CONCLUSIONS: We observed longer PPS in patients continuing cabozantinib beyond PD, suggesting that this could be an effective option.

Role of Bone Metastases in Patients Receiving Immunotherapy for Pre-Treated Urothelial Carcinoma: The Multicentre, Retrospective Meet-URO-1 Bone Study.

BACKGROUND: Considerable numbers of patients with metastatic urothelial carcinoma (mUC) develop bone metastases (BoM). Their impact on the efficacy of immune-checkpoint inhibitors (ICIs) is not yet investigated. METHODS: Between July 2014 and August 2020 data on pts treated with single-agent ICIs after failure of at least 1 previous line of chemotherapy for advanced disease, were retrospectively collected across 14 Italian centers. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Cox regression analysis was performed evaluating potential prognostic factors for OS and PFS. Each factor was evaluated in univariable (UVA) and multivariable analysis (MVA). RESULTS: A total of 208 evaluable patients treated with ICIs were identified, including 122 (59%) without BoM (BoM-) and 86 (41%) with bone metastases (BoM+). After a median follow-up of 22.3 months, BoM+ patients showed shorter OS (median 3.9 vs 7.8 months, HR 1.59 [95%CI, 1.15-2.20], P = .005) and shorter PFS (median 2.0 vs 2.6 months, HR 1.76 [95%CI, 1.31-2.37], P < .001). Probability of being alive was 62% vs 40% after 6 months, 38% vs 23% after 1 year and 24% vs 13% after 2 years, in BoM- and BoM+ respectively. Within each Bellmunt score, OS and PFS of BoM+ patients were shorter. Both presence of BoM and higher Bellmunt risk score were significantly associated with shorter OS and PFS in UVA and MVA. CONCLUSION: Patients treated with single-agent ICIs for BoM+ mUC have a dismal prognosis compared to BoM-. Further research is needed to understand the mechanism behind these outcomes.

Different semantic and affective meaning of the words associated to physical and social pain in cancer patients on early palliative/supportive care and in healthy, pain-free individuals.

Early palliative/supportive care (ePSC) is a medical intervention focused on patient's needs, that integrates standard oncological treatment, shortly after a diagnosis of advanced/metastatic cancer. ePSC improves the appropriate management of cancer pain. Understanding the semantic and emotional impact of the words used by patients to describe their pain may further improve its assessment in the ePSC setting. Psycholinguistics assumes that the semantic and affective properties of words affect the ease by which they are processed and comprehended. Therefore, in this cross-sectional survey study we collected normative data about the semantic and affective properties of words associated to physical and social pain, in order to investigate how patients with cancer pain on ePSC process them compared to healthy, pain-free individuals. One hundred ninety patients and 124 matched controls rated the Familiarity, Valence, Arousal, Pain-relatedness, Intensity, and Unpleasantness of 94 words expressing physical and social pain. Descriptive and inferential statistics were performed on ratings in order to unveil patients' semantic and affective representation of pain and compare it with those from controls. Possible effects of variables associated to the illness experience were also tested. Both groups perceived the words conveying social pain as more negative and pain-related than those expressing physical pain, confirming previous evidence of social pain described as worse than physical pain. Patients rated pain words as less negative, less pain-related, and conveying a lower intense and unpleasant pain than controls, suggesting either an adaptation to the pain experience or the role played by ePSC in improving patients' ability to cope with it. This exploratory study suggests that a chronic pain experience as the one experienced by cancer patients on ePSC affects the semantic and affective representation of pain words.

Impact of Previous Nephrectomy on Clinical Outcome of Metastatic Renal Carcinoma Treated With Immune-Oncology: A Real-World Study on Behalf of Meet-URO Group (MeetUro-7b).

BACKGROUND: Immune-Oncology (IO) improves Overall Survival (OS) in metastatic Renal Cell Carcinoma (mRCC). The prognostic impact of previous Cytoreductive Nephrectomy (CN) and radical nephrectomy (RN), with curative intent, in patients treated with IO is not well defined. The aim of our paper is to evaluate the impact of previous nephrectomy on outcome of mRCC patients treated with IO. METHODS: 287 eligible patients were retrospectively collected from 16 Italian referral centers adhering to the MeetUro association. Patients treated with IO as second and third line were included, whereas patients treated with IO as first line were excluded. Kaplan-Meier method and log-rank test were performed to compare Progression Free Survival (PFS) and OS between groups. In our analysis, both CN and RN were included. The association between nephrectomy and other variables was analyzed in univariate and multivariate setting using the Cox proportional hazard model. RESULTS: 246/287 (85.7%) patients had nephrectomy before IO treatment. Median PFS in patients who underwent nephrectomy (246/287) was 4.8 months (95%CI 3.9-5.7) vs 3.7 months (95%CI 1.9-5.5) in patients who did not it (HR log rank 0.78; 95%CI 0.53 to 1.15; p = 0.186). Median OS in patients who had previous nephrectomy (246/287) was 20.9 months (95%CI 17.6-24.1) vs 13 months (95%CI 7.7-18.2) in patients who did not it (HR log rank 0.504; 95%CI 0.337 to 0.755; p = 0.001). In the multivariate model, nephrectomy showed a significant association with OS (HR log rank 0.638; 95%CI 0.416 to 0.980), whereas gland metastases were still associated with better outcome in terms of both OS (HR log rank 0.487; 95%CI 0.279 to 0.852) and PFS (HR log rank 0.646; 95%CI 0.435 to 0.958). CONCLUSIONS: IO treatment, in patients who had previously undergone nephrectomy, was associated with a better outcome in terms of OS. Further prospective trials would assess this issue in order to guide clinicians in real word practice.

Clinical Outcomes of Patients With Metastatic Urothelial Carcinoma After Progression to Immune Checkpoint Inhibitors: A Retrospective Analysis by the Meet-Uro Group (Meet-URO 1 Study).

BACKGROUND: Immune checkpoint inhibitors (ICIs) are currently the standard of care for metastatic urothelial cancer (mUC) after the failure of previous platinum-based chemotherapy. The choice of further therapy after ICI progression is a new challenge, and scarce data support it. We aimed to examine the outcomes of mUC patients after progression to ICI, especially when receiving chemotherapy. METHODS: Data were retrospectively collected from clinical records of mUC patients whose disease progressed to anti-programmed death 1 (PD-1)or programmed death ligand 1 (PD-L1) therapy at 14 Italian centers. Patients were grouped according to ICI therapy setting into SALVAGE (ie, ICI delivered ⩾ second-line therapy after platinum-based chemotherapy) and NAÏVE (ie, first-line therapy) groups. Progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared among subgroups. Cox regression assessed the effect of treatments after progression to ICI on OS. Objective response rate (ORR) was calculated as the sum of partial and complete radiologic responses. RESULTS: The study population consisted of 201 mUC patients who progressed after ICI: 59 in the NAÏVE cohort and 142 in the SALVAGE cohort. Overall, 52 patients received chemotherapy after ICI progression (25.9%), 20 (9.9%) received ICI beyond progression, 115 (57.2%) received best supportive care only, and 14 (7.0%) received investigational drugs. Objective response rate to chemotherapy in the post-ICI setting was 23.1% (28.0% in the NAÏVE group and 18.5% in the SALVAGE group). Median PFS and OS to chemotherapy after ICI-PD was 5 months (95% confidence interval [CI]: 3-11) and 13 months (95% CI: 7-NA) for the NAÏVE group; 3 months (95% CI: 2-NA) and 9 months (95% CI: 6-NA) for the SALVAGE group, respectively. Overall survival from ICI initiation was 17 months for patients receiving chemotherapy (hazard ratio [HR] = 0.09, p < 0.001), versus 8 months for patients receiving ICI beyond progression (HR = 0.13, p < 0.001), and 2 months for patients who did not receive further active treatment (p < 0.001). CONCLUSIONS: Chemotherapy administered after ICI progression for mUC patients is advisable irrespective of the treatment line.

Clinical Outcomes of Metastatic Renal Carcinoma Following Disease Progression to Programmed Death (PD)-1 or PD-L1 Inhibitors (IO): A Meet-URO Group Real World Study (Meet-Uro 7).

OBJECTIVES: The aim of our study was to collect data about of the outcome of metastatic renal cell carcinoma patients who progressed after immune checkpoint inhibitors in order to enhance data about efficacy and safety of treatment beyond immune-oncology (IO). MATERIALS AND METHODS: A total of 162 eligible patients, progressing to IO, were enrolled from 16 Italian referral centers adhering to the Meet-Uro association. Baseline characteristics, outcome data and toxicities were retrospectively collected. Descriptive analysis was made using median values and ranges. Kaplan-Meier method and Mantel-Haenszel log-rank test were performed to compare differences between groups. RESULTS: A total of 111 patients (68.5%) were treated after IO progression. In all, 51 patients (31.5%) did not receive further treatment for clinical deterioration. Median IO progression free survival (PFS) was 4 months (95% confidence interval [CI]: 3.1-4.8). IO-PFS tends to be longer in patients reporting adverse events (AE) of any grade (5.03 [95% CI: 3.8-6.1] vs. 2.99 [95% CI: 2.4-3.5] months P=0.004). Subsequent therapies included cabozantinib (n=79, 48%), everolimus (n=11, 6.7%), and others (n=21, 12.9%).Median PFS post-IO was 6.5 months (95% CI: 5.1-7.8). Cabozantinib showed longer PFS compared with everolimus (7.6 mo [95% CI: 5.2-10.1] vs. 3.2 mo [95% CI: 1.8-4.5]) (hazard ratio: 0.2; 95% CI: 0.1026-0.7968) and other drugs (4.3 mo [95% CI: 1.3-7.4]) (hazard ratio: 0.6; 95% CI: 0.35-1.23). All grade AE were reported in 83 patients (74%) and G3 to G4 AE in 39 patients (35%). Target therapies post-IO showed median overall survival of 14.7 months (95% CI: 0.3-21.4). CONCLUSIONS: In our real world experience after progression to IO, vascular endotelial groth factor-tyrosine kinase inhibitors, given to patients, proved to be active and safe choices. Cabozantinib was associated with a better outcome in terms of median PFS.