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Dyspnea is one of the most common and distressing symptoms in patients with cancer and noncancer advanced diseases. The Japanese Society for Palliative Medicine revised previous guidelines for the management of respiratory symptoms in patients with cancer and newly developed clinical guidelines for managing dyspnea in patients with advanced disease, based on the result of systematic reviews for each clinical question and consensus among experts. We describe the recommendations of the guidelines as well as provide insights into the reasoning behind the recommendations and their development process. There has been a paucity of evidence regarding the interventions for dyspnea in patients with advanced disease. Thus, more clinical research that includes not only randomized controlled trials but also real-world observational studies is warranted. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Oculopharyngodistal myopathy type 4 (OPDM4) arises from a CGG repeat expansion in the 5′ UTR of the RILPL1 gene. Reported cases of OPDM4 have been limited. The aim of this study was to investigate the clinical and myopathological characteristics of OPDM4 patients with advanced disease. Methods: We assessed a total of 8 affected and 12 unaffected individuals in an OPDM4 family with autosomal dominant inheritance. Muscle biopsy tissue from the proband underwent histological, enzyme histochemical, and immunohistochemical stains, and electron microscopy analysis. Whole exome sequencing and repeat primer PCR (RP‐PCR) were conducted to investigate underlying variants. Results: OPDM4 patients displayed a progressive disease course. Most experienced lower limb weakness and diminished walking ability in their 20s and 30s, followed by ptosis, ophthalmoplegia, swallowing difficulties, and dysarthria in their 30s to 50s, By their 50s to 70s, they became non‐ambulatory. Muscle magnetic resonance imaging (MRI) of the proband in advanced disease revealed severe fatty infiltration of pelvic girdle and lower limb muscles. Biopsied muscle tissue exhibited advanced changes typified by adipose connective tissue replacement and the presence of multiple eosinophilic and p62‐positive intranuclear inclusions. Immunopositivity for the intranuclear inclusions was observed with anti‐glycine antibody and laboratory‐made polyA‐R1 antibody. RP‐PCR unveiled an abnormal CGG repeat expansion in the 5′ UTR of the RILPL1 gene. Discussion: The clinical and radiological features in this family broaden the phenotypic spectrum of OPDM4. The presence of intranuclear inclusions in the proliferative adipose connective tissues of muscle biopsy specimens holds diagnostic significance for OPDM4 in advanced disease. [ABSTRACT FROM AUTHOR]

Caring for a parent during emerging adulthood may be a disruptive and non-normative experience. Despite the growing prevalence of emerging adult (EA) caregivers, there remains limited research. We explored the experiences of EAs caring for parents living with advanced disease. Interviews were conducted with 12 EA daughters and analyzed using constructivist grounded theory. The core category was identified as negotiating accelerated adulthood, a dynamic interplay between feeling more of an adult than before and the paradoxical feeling of I'm not where I should be. Prior to the core category, participants' caregiving role is assumed. Availability of support influenced participants' process of negotiating accelerated adulthood. Findings highlight the uniqueness and developmental impact of this experience. Results suggest an interplay of different factors with how the role is assumed, appraised, and experienced by EA daughters. Greater awareness of these experiences may inform the development of tailored interventions and strategies for EA caregivers. [ABSTRACT FROM AUTHOR]

There is limited information on the treatment trajectory and outcomes of patients with advanced cEGFRm NSCLC treated with osimertinib in routine clinical practice in Canada. By using and analyzing population-based administrative data and detailed chart abstraction in the province of Alberta, our objective was to capture Canadian-specific real-world treatment patterns, health outcomes, and healthcare resource utilization (HCRU) in advanced cEGFRm NSCLC patients who were (a) treated with osimertinib and (b) those receiving treatment after osimertinib. In our study cohort, we found that the overall survival rates for real-world patients receiving osimertinib were less favorable than those observed in clinical trials (24.0 versus 38.6 months). The attrition rate after osimertinib was substantial and high HCRU persisted across many years after diagnosis and treatment. This study provides important real-world evidence on contemporary survival, treatment patterns, and healthcare use among cEGFRm NSCLC patients treated with osimertinib and suggests that further research efforts are needed to improve therapeutic options in both the first and subsequent line settings.

There is limited information on the treatment trajectory and outcomes of patients with advanced cEGFRm NSCLC treated with osimertinib in routine clinical practice in Canada. By using and analyzing population-based administrative data and detailed chart abstraction in the province of Alberta, our objective was to capture Canadian-specific real-world treatment patterns, health outcomes, and healthcare resource utilization (HCRU) in advanced cEGFRm NSCLC patients who were (a) treated with osimertinib and (b) those receiving treatment after osimertinib. In our study cohort, we found that the overall survival rates for real-world patients receiving osimertinib were less favorable than those observed in clinical trials (24.0 versus 38.6 months). The attrition rate after osimertinib was substantial and high HCRU persisted across many years after diagnosis and treatment. This study provides important real-world evidence on contemporary survival, treatment patterns, and healthcare use among cEGFRm NSCLC patients treated with osimertinib and suggests that further research efforts are needed to improve therapeutic options in both the first and subsequent line settings. [ABSTRACT FROM AUTHOR]

Background Advance care planning (ACP) aims to ensure that people with chronic or advanced disease receive medical care that is consistent with their values and preferences. However, professionals may find it challenging to engage these patients in conversations about the end of life. We sought to develop a pictorial tool to facilitate communication around ACP. Methods This was a three-phase study. In phase 1, we used the nominal group and Delphi techniques to achieve expert consensus regarding the conceptual content of the tool. In phase 2, a professional cartoonist was commissioned to create a series of cartoons representing each of the content areas resulting from the Delphi process. The pictorial tool was then administered (phase 3) with a sample of individuals with advanced/chronic disease to explore whether the cartoons were easy to understand and conveyed the intended message. Results Following a three-round Delphi process, consensus was reached regarding a set of 12 key content areas that should be considered in the context of an ACP interview. The cartoons created to represent each of the 12 areas were then reviewed and ordered so as to reflect the typical stages of an end-of-life care interview. After administering the pictorial tool with 24 frail older adults with advanced/chronic disease, changes were made to 9 of the 12 cartoons. Conclusions The new pictorial tool comprises a set of 12 cartoons that can guide professionals as they seek to engage frail older adults with advanced/chronic disease in conversations about the end of life and ACP. [ABSTRACT FROM AUTHOR]

Cameroon is a low-and-middle income country (LMIC) with one of the highest incidence and mortality from cervical cancer in Africa. In this Central African country where the prevalence of human immunodeficiency virus (HIV) is high and the screening coverage is low, cervical cancer is the most deadly and the second most common cancer among women. Notwithstanding the growing burden of cervical cancer in Cameroon, most patients - often of lower socioeconomic status - continue to encounter multi-level barriers to timely and adequate care. These include the lack of physical and financial access to healthcare facilities, limited quality pathology, imaging and treatment services, ignorance of disease by the population, shortage of a well-trained oncology workfroce, which result in significant delays in gaining access to screening, diagnosis, treatment and care. This paper presents 3 cases of patients with advanced cervical cancer who had surgery (hysterectomy) as primary treatment, without appropriate post-surgical investigation to further specify disease stage, persistence of residual disease, and need for adjuvant chemoradiation. Pathology services and diagnostic imaging procedures remain scarce and underused in LMIC countries like Cameroon. Healthcare professionals involved in patient care lack adequate knowledge, skills and collaborative strategy to properly navigate these patients. To address these challenges, the health system should be reinforced with adequate infrastructures, sustainable funding should be secured to enhance universal health coverage and promote cancer prevention and control programs, multidisciplinary teams and coordination of care among providers should be improved, and relevant health indicators should be put in place to better monitor the quality of care delivered to patients who are mostly vulnerable and uninformed.

Abstract Many studies have focused on the prognostic role of soluble programmed death ligand 1 (sPD-L1) in non-small cell lung cancer (NSCLC), but outcomes are ambiguous and further investigations are needed. We addressed the matter by studying sPD-L1 in baseline samples and in longitudinal samples taken prior to three subsequent cycles of anti-PD-1/anti-PD-L1 treatments. Eighty patients with NSCLC were enrolled. Median sPD-L1 level at baseline was 52 pg/mL [95% confidence interval (CI) 49–57]. In patients treated with pembrolizumab and nivolumab, the concentration of sPD-L1 remained rather stable throughout treatment. In contrast, sPD-L1 rose by 50-fold following the first cycle of atezolizumab therapy. We found the baseline level of sPD-L1 to be related to overall survival (OS) after two years of follow-up in simple Cox analysis (p = 0.006) and multiple Cox Regression, hazard ratio 1.02 (95% CI 1.00–1.03) (p = 0.033). There was no association between sPD-L1 and tissue PD-L1 expression, overall response rate, or progression free survival. In conclusion, sPD-L1 measured in baseline serum samples may be associated with OS in NSCLC patients receiving anti-PD1/anti-PD-L1 treatment. Importantly, the results signify that further research is warranted to explore the clinical utility of sPD-L1 in patients treated with anti-PD-L1.

Background: In the era of immune checkpoint blockade, the role of cancer vaccines in immune priming has provided additional potential for therapeutic improvements. Prior studies have demonstrated delayed type hypersensitivity and anti-tumor immunity with vaccines engineered to secrete granulocytemacrophage colony-stimulating factor (GM-CSF). The safety, efficacy and antitumor immunity of GM-CSF secreting vaccine in patients with previously treated stage III or IV melanoma needs further investigation. Methods: In this phase II trial, excised lymph node metastases were processed to single cells, transduced with an adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines were composed of 1x106, 4x106, or 1x107 tumor cells, and were injected intradermally and subcutaneously at weekly and biweekly intervals. The primary endpoints were feasibility of producing vaccine in stage III patients and determining the proportion of patients alive at two years in stage IV patients. Results: GM-CSF vaccine was successfully developed and administered in all 61 patients. Toxicities were restricted to grade 1-2 local skin reactions. The median OS for stage III patients (n = 20) was 71.1 (95% CI, 43.7 to NR) months and 14.9 (95%CI, 12.1 to 39.7) months for stage IV patients. The median PFS in stage III patients was 50.7 (95%CI, 36.3 to NR) months and 4.1 (95% CI, 3.0-6.3) months in stage IV patients. In the overall population, the disease control rate was 39.3% (95%CI, 27.1 to 52.7%). In stage III patients, higher pre-treatment plasma cytokine levels of MMP-1, TRAIL, CXCL-11, CXCL-13 were associated with improved PFS (p<0.05 for all). An increase in post-vaccination levels of IL-15 and TRAIL for stage III patients was associated with improved PFS (p=0.03 for both). Similarly, an increase in post-vaccination IL-16 level for stage IV patients was associated with improved PFS (p=0.02) and clinical benefit. Conclusions: Vaccination with autologous melanoma cells secreting GM-CSF augments antitumor immunity in stage III and IV patients with melanoma, is safe, and demonstrates disease control. Luminex data suggests that changes in inflammatory cytokines and immune cell infiltration promote tumor antigen presentation and subsequent tumor cell destruction. Additional investigation to administer this vaccine in combination with immune checkpoint inhibitors is needed. [ABSTRACT FROM AUTHOR]

Many studies have focused on the prognostic role of soluble programmed death ligand 1 (sPD-L1) in non-small cell lung cancer (NSCLC), but outcomes are ambiguous and further investigations are needed. We addressed the matter by studying sPD-L1 in baseline samples and in longitudinal samples taken prior to three subsequent cycles of anti-PD-1/anti-PD-L1 treatments. Eighty patients with NSCLC were enrolled. Median sPD-L1 level at baseline was 52 pg/mL [95% confidence interval (CI) 49–57]. In patients treated with pembrolizumab and nivolumab, the concentration of sPD-L1 remained rather stable throughout treatment. In contrast, sPD-L1 rose by 50-fold following the first cycle of atezolizumab therapy. We found the baseline level of sPD-L1 to be related to overall survival (OS) after two years of follow-up in simple Cox analysis (p = 0.006) and multiple Cox Regression, hazard ratio 1.02 (95% CI 1.00–1.03) (p = 0.033). There was no association between sPD-L1 and tissue PD-L1 expression, overall response rate, or progression free survival. In conclusion, sPD-L1 measured in baseline serum samples may be associated with OS in NSCLC patients receiving anti-PD1/anti-PD-L1 treatment. Importantly, the results signify that further research is warranted to explore the clinical utility of sPD-L1 in patients treated with anti-PD-L1. [ABSTRACT FROM AUTHOR]

Objective: Despite the relatively high cure rates in early-stage breast cancer, advanced and metastatic breast cancer cases are associated with more inauspicious patient outcomes. Fortunately, with the advent of cyclin-dependent kinase (CDK)4/6 inhibitors (e.g. palbociclib, ribociclib, and abemaciclib) with endocrine therapy, survival in advanced and metastatic breast cancer has appreciably improved. In the current review, we discuss these distinctions and the concomitant implications associated with the individual CDK4/6 inhibitors. Data sources: We conducted an extensive PubMed search comprising several review articles on the topic of advanced or metastatic breast cancer treatment, with specific terms that included CDK4/6 inhibitors, treatment, and breast cancer. Data summary: Palbociclib, ribociclib, and abemaciclib have exhibited superior progression-free survival differences compared to endocrine therapy alone. However, there are differences among the various CDK4/6 inhibitors with regard to overall survival, tolerability and quality of life. Conclusions: Ribociclib may be indicated for pre/perimenopausal patients, whereas abemaciclib is potentially recommended to address endocrine-resistant or visceral disease. Alternatively, palbociclib is associated with lower discontinuation rates than abemaciclib and unlike ribociclib, QTc prolongation is not observed with palbociclib. [ABSTRACT FROM AUTHOR]

Population level data examining the relationship between chronic glucocorticoid use and risk for advanced prostate cancer (PCa). Chronic glucocorticoid exposure was associated with a significantly higher risk of advanced PCa at presentation. Given the widespread use of glucocorticoids, it is important to consider the role steroids may play in PCa pathogenesis. Background: Examine the relationship between exposure to systemic glucocorticoids (steroids) and advanced prostate cancer (PCa) at presentation. Prior work suggested that steroid use may be associated with increased PCa risk. Materials and Methods: We queried the linked SEER-Medicare database (2004-2015) to identify PSA screened patients diagnosed with PCa. Cr iter ia for screening included a PSA lab test or DRE exam in both the 12 month and 13 to 36 month per iods pr ior to diagnosis of PCa. Steroid exposure was determined using Medicare Part D and groups were divided based on duration of use in the 3 years prior to diagnosis: controls with no exposure, < 30 days, 30 days - 1 year, 1 to 2 years, and > 2 + years. Advanced PCa was defined as systemic metastases or regional lymph node metastasis at presentation. Risk estimates for advanced PCa at presentation for steroid exposure groups vs. controls were assessed with univariable and multivariable logistic regression models. Results: We identified 22,920 PSA screened patients diagnosed with PCa of which 29% used glucocorticoids in the exposure period. The mean (SD) duration for glucocorticoid use (in days) among all steroid users was 76.7 days (192.1). On univariable and multivariable analyses, > 2 years of steroid exposure was associated with significantly increased risk for advanced PCa (OR 2.06, 95% CI 1.35-3.14 and OR 1.74, 95% CI 1.12-2.69, respectively). Conclusion: In this population-based PSA-screened cohort, prolonged steroid use was associated with increased risk of advanced PCa at diagnosis. With the widespread use of glucocorticoids, it is important to consider the role steroids may play in PCa pathogenesis. [ABSTRACT FROM AUTHOR]

Simple Summary: Local therapies (LTs) are suggested by most experts and guidelines for the treatment of advanced ACC. However, there are only a few published studies on LTs, and there are no clear recommendations regarding which patients benefit from which treatments. Therefore, this multicentre cohort study aimed to investigate the outcomes and factors associated with LTs (n = 132) when used as a therapeutic approach in 66 patients with metastatic ACC. These patients were treated with local thermal ablation (LTA, n = 84) therapies, transarterial (chemo)embolisation (TA(C)E, n = 40), and transarterial radioembolisation (TARE, n = 8). In 21% of the treated tumoural lesions, complete remission was achieved. Time to progression of the treated lesion was particularly long in patients treated with LTA (median not yet reached), whereas it was only 8.3 months after TA(C)E and 8.2 months after TARE. Thus, this study provides clear evidence that LTs can be quite efficient in a subgroup of patients with advanced ACC. International guidelines recommend local therapies (LTs) such as local thermal ablation (LTA; radiofrequency, microwave, cryoablation), transarterial (chemo)embolisation (TA(C)E), and transarterial radioembolisation (TARE) as therapeutic options for advanced adrenocortical carcinoma (ACC). However, the evidence for these recommendations is scarce. We retrospectively analysed patients receiving LTs for advanced ACC. Time to progression of the treated lesion (tTTP) was the primary endpoint. The secondary endpoints were best objective response, overall progression-free survival, overall survival, adverse events, and the establishment of predictive factors by multivariate Cox analyses. A total of 132 tumoural lesions in 66 patients were treated with LTA (n = 84), TA(C)E (n = 40), and TARE (n = 8). Complete response was achieved in 27 lesions (20.5%; all of them achieved by LTA), partial response in 27 (20.5%), and stable disease in 38 (28.8%). For the LTA group, the median tTTP was not reached, whereas it was reached 8.3 months after TA(C)E and 8.2 months after TARE (p < 0.001). The median time interval from primary diagnosis to LT was >47 months. Fewer than four prior therapies and mitotane plasma levels of >14 mg/L positively influenced the tTTP. In summary, this is one of the largest studies on LTs in advanced ACC, and it demonstrates a very high local disease control rate. Thus, it clearly supports the guideline recommendations for LTs in these patients. [ABSTRACT FROM AUTHOR]

International guidelines emphasise the role of local therapies (LT) for the treatment of advanced adrenocortical carcinoma (ACC). However, large studies are lacking in this field. Therefore, we performed a review of the literature to synthesise current evidence and develop clinical guidance. PubMed database was searched for systematic literature. We identified 119 potentially relevant articles, of which 21 could be included in our final analysis. All were retrospective and reported on 374 patients treated with LT for advanced ACC (12 studies on radiotherapy, 3 on transarterial chemoembolisation and radioembolisation, 4 on image-guided thermal ablation [radiofrequency, microwave ablation, and cryoablation, and two studies reporting treatment with several different LT]). Radiotherapy was frequently performed with palliative intention. However, in most patients, disease control and with higher dosage also partial responses could be achieved. Data for other LT were more limited, but also point towards local disease control in a significant percentage of patients. Very few studies tried to identify factors that are predictive on response. Patients with a disease-free interval after primary surgery of more than 9 months and lesions<5 cm might benefit most. Underreporting of toxicities may be prevalent, but LT appear to be relatively safe overall. Available evidence on LT for ACC is limited. LT appears to be safe and effective in cases with limited disease and should be considered depending on local expertise in a multidisciplinary team discussion. [ABSTRACT FROM AUTHOR]

BackgroundIn the era of immune checkpoint blockade, the role of cancer vaccines in immune priming has provided additional potential for therapeutic improvements. Prior studies have demonstrated delayed type hypersensitivity and anti-tumor immunity with vaccines engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF). The safety, efficacy and anti-tumor immunity of GM-CSF secreting vaccine in patients with previously treated stage III or IV melanoma needs further investigation.MethodsIn this phase II trial, excised lymph node metastases were processed to single cells, transduced with an adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines were composed of 1x106, 4x106, or 1x107 tumor cells, and were injected intradermally and subcutaneously at weekly and biweekly intervals. The primary endpoints were feasibility of producing vaccine in stage III patients and determining the proportion of patients alive at two years in stage IV patients.ResultsGM-CSF vaccine was successfully developed and administered in all 61 patients. Toxicities were restricted to grade 1-2 local skin reactions. The median OS for stage III patients (n = 20) was 71.1 (95% CI, 43.7 to NR) months and 14.9 (95%CI, 12.1 to 39.7) months for stage IV patients. The median PFS in stage III patients was 50.7 (95%CI, 36.3 to NR) months and 4.1 (95% CI, 3.0-6.3) months in stage IV patients. In the overall population, the disease control rate was 39.3% (95%CI, 27.1 to 52.7%). In stage III patients, higher pre-treatment plasma cytokine levels of MMP-1, TRAIL, CXCL-11, CXCL-13 were associated with improved PFS (p

PURPOSE: Men with advanced prostate cancer experience a wide range of side effects from the cancer and its therapies, which have a negative effect on their quality of life (QOL). Few studies have evaluated supportive care needs in these individuals. The purpose of this study was to conduct a holistic supportive care needs assessment among these survivors guided by the Supportive Care Framework for Cancer Care. METHODS: Using a convergent parallel mixed-methods approach, prostate cancer survivors with advanced disease (n = 188) completed a cross-sectional survey. A subset of these survivors (n = 20) participated in an interview to further explore their experience of unmet needs. RESULTS: Survivors reported unmet supportive care needs in every domain of the framework. Up to 95.2% of the survivors had at least one unmet need, with a mean of 14.9 (range: 0-42). Several areas of convergence among the quantitative and qualitative data (fatigue, sexual dysfunction, practical, and emotional/psychological domains), as well as divergence (informational and spiritual domains, depression, urinary dysfunction) were found through the integration process. CONCLUSIONS: This study confirms that prostate cancer survivors with advanced disease experience high rates of unmet supportive care needs. The findings also highlight the diversity of those unmet needs. These results may assist with future development of patient-centered supportive care interventions that better meet the specific needs of this vulnerable group of cancer survivors.

Abstract Background The associations of adiposity with aggressive prostate cancer risk are unclear. Using two‐sample Mendelian randomization, we assessed the association of metabolically unfavourable adiposity (UFA), favourable adiposity (FA) and for comparison body mass index (BMI), with prostate cancer, including aggressive prostate cancer. Methods We examined the association of these genetically predicted adiposity‐related traits with risk of prostate cancer overall, aggressive and early onset disease using outcome summary statistics from the PRACTICAL consortium (including 15,167 aggressive cases). Results In inverse‐variance weighted models, there was little evidence that genetically predicted one standard deviation higher UFA, FA and BMI were associated with aggressive prostate cancer [OR: 0.85 (95% CI:0.61–1.19), 0.80 (0.53–1.23) and 0.97 (0.88–1.08), respectively]; these associations were largely consistent in sensitivity analyses accounting for horizontal pleiotropy. There was no strong evidence that genetically determined UFA, FA or BMI were associated with overall prostate cancer or early age of onset prostate cancer. Conclusions We did not find differences in the associations of UFA and FA with prostate cancer risk, which suggest that adiposity is unlikely to influence prostate cancer via the metabolic factors assessed; however, these did not cover some aspects related to metabolic health that may link obesity with aggressive prostate cancer, which should be explored in future studies.

Abstract Background Pain is a significant problem for many people with advanced disease or a serious illness. Culture and ethnicity can affect the experience and management of pain. However, there is limited research in South Asian communities in the UK on their experiences of pain. The aim of this study is to explore the experiences and attitudes of patients and family carers from South Asian communities about pain and its management within advanced disease or serious illness. Methods Qualitative thematic analysis based on descriptive phenomenology (Sundler et al. 2019). Qualitative semi-structured interviews with patients or family carers from South Asian communities (N = 15). Interviews were recorded, transcribed and analysed using an inductive approach. Public and Patient Involvement representatives from British South Asian communities were consulted for guidance. Results There were five key themes from the interviews: The importance of communication about pain with healthcare professionals; Concerns about taking pain medication; Personal resilience, privacy and self-management; Gender, culture and pain; Home pain management as struggle and frustration. Conclusion To improve pain management for people from South Asian communities with advanced disease or a serious illness, there are a number of important issues for healthcare professionals from palliative and primary care services to address. These include: greater awareness around people’s fears and concerns about pain medication; their potential use of alternative pain management strategies; and cultural issues such as resilience, privacy, dignity and gender roles. Effective communication between doctors, patients and family members could be improved by using a ‘cultural humility’ model; providing clear and accessible pain medication information; understanding and taking account of people with both low, and medium levels, of English language proficiency; and improving patient trust. Additionally, improvements to out of hours services could improve pain management for all patients managing their pain at home.

Lymphoedema is thought to affect around 200 000 people in the UK (NHS England, 2023). Secondary lymphoedema is a relatively common complication of cancer and cancer treatment, and in advanced disease it may present a challenging issue for community nursing staff caring for patients approaching the end of their lives. In this article, a case study considers the assessment and treatment of upper limb lymphoedema in a patient with advanced metastatic breast cancer. Management of this complex and distressing condition requires holistic assessment and collaborative care planning with the patient and their wider care team, including onward referral to specialist lymphoedema and palliative care services. The case study considers the typical presentation of lymphoedema in an upper limb, exclusion of reversible causes for oedema, awareness of palliative care emergencies such as superior vena cava obstruction, and the provision of supportive therapeutic interventions in context of the patient's expressed wishes for her ongoing care. [ABSTRACT FROM AUTHOR]

Simple Summary: This systematic review was conducted using four public electronic databases (PubMed, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials) from the date of inception to 31 May 2023, and 10 original articles with information regarding neoadjuvant chemotherapy (NACT) for malignant ovarian germ cell tumors (MOGCT) were identified. The results of the meta-analysis showed that NACT was used in approximately 40% of advanced MOGCT cases, with a response rate of 95.8%. The uterine preservation rate was approximately 70%, and the cumulative resumed menstruation rate was 100% (n = 30). Four comparator studies evaluating NACT versus primary debulking surgery between the groups showed similar overall survival, disease-free survival, recurrence rate, and adverse event rate (grade 3–4) from chemotherapy. Although available data are limited and level I evidence is lacking, we believe that NACT may be feasible for advanced MOGCT. Further studies are required to confirm this study's results. Randomized clinical trials assessing the efficacy of neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer have predominantly included women with high-grade serous carcinomas. The response rate and oncological outcomes of NACT for malignant ovarian germ cell tumors (MOGCT) are poorly understood. This study aimed to examine the effects of NACT on women with MOGCT by conducting a systematic review of four public search engines. Fifteen studies were identified, and a further descriptive analysis was performed for 10 original articles. In those studies, most women were treated with a bleomycin, etoposide, and cisplatin regimen, and one to three cycles were used in most studies. Four studies comparing NACT and primary debulking surgery showed similar complete response rates (n = 2; pooled odds ratio [OR] 0.90, 95% confidence interval [CI] 0.15–5.27), comparable overall survival (n = 3; 87.0–100% versus 70.0–100%), disease-free survival (n = 3; 87.0–100% versus 70.0–100%), recurrence rate (n = 1; OR 3.50, 95%CI 0.38–32.50), and adverse events rate from chemotherapy between the groups. In conclusion, NACT may be considered for the management of MOGCT; however, possible candidates for NACT use and an ideal number of NACT cycles remain unknown. Further studies are warranted to validate the efficacy of NACT in advanced MOGCT patients. [ABSTRACT FROM AUTHOR]

Acrometastasis, especially in the hands and fingers, is a rare clinical condition resulting from primary cancers such as lung, breast, kidney, and, rarely, thyroid cancer. Acrometastasis tends to be the tip of the iceberg in patients with extensive systemic disease, which could be regional, pulmonary, skeletal, neurological, or all of them combined. Even though these tumors are clearly visible and symptomatic, the diagnosis is usually misleading because such distal metastatic disease is not thought of at first. In general, systemic treatments should be given to any patient presenting digital acrometastasis. We describe two cases of papillary thyroid carcinoma and digital acrometastasis as a sign of advanced disease. [ABSTRACT FROM AUTHOR]

Abstract Background Advance care planning (ACP) is the process supporting individuals with life-limiting illness to make informed decisions about their future healthcare. Ethnic disparities in ACP have been widely highlighted, but interpretation is challenging due to methodological heterogeneity. This review aims to examine differences in the presence of documented ACP in individuals’ care records for people with advanced disease by ethnic group, and identify patient and clinician related factors contributing to this. Methods Mixed-methods systematic review. Keyword searches on six electronic databases were conducted (01/2000–04/2022). The primary outcome measure was statistically significant differences in the presence of ACP in patients’ care records by ethnicity: quantitative data was summarised and tabulated. The secondary outcome measures were patient and clinician-based factors affecting ACP. Data was analysed qualitatively through thematic analysis; themes were developed and presented in a narrative synthesis. Feedback on themes was gained from Patient and Public Involvement (PPI) representatives. Study quality was assessed through Joanna Briggs Institute Critical Appraisal tools and Gough’s Weight of Evidence. Results N=35 papers were included in total; all had Medium/High Weight of Evidence. Fifteen papers (comparing two or more ethnic groups) addressed the primary outcome measure. Twelve of the fifteen papers reported White patients had statistically higher rates of formally documented ACP in their care records than patients from other ethnic groups. There were no significant differences in the presence of informal ACP between ethnic groups. Nineteen papers addressed the secondary outcome measure; thirteen discussed patient-based factors impacting ACP presence with four key themes: poor awareness and understanding of ACP; financial constraints; faith and religion; and family involvement. Eight papers discussed clinician-based factors with three key themes: poor clinician confidence around cultural values and ideals; exacerbation of institutional constraints; and pre-conceived ideas of patients’ wishes. Conclusions This review found differences in the presence of legal ACP across ethnic groups despite similar presence of informal end of life conversations. Factors including low clinician confidence to deliver culturally sensitive, individualised conversations around ACP, and patients reasons for not wishing to engage in ACP (including, faith, religion or family preferences) may begin to explain some documented differences. Trial registration PROSPERO-CRD42022315252.

Background: The associations of adiposity with aggressive prostate cancer risk are unclear. Using two‐sample Mendelian randomization, we assessed the association of metabolically unfavourable adiposity (UFA), favourable adiposity (FA) and for comparison body mass index (BMI), with prostate cancer, including aggressive prostate cancer. Methods: We examined the association of these genetically predicted adiposity‐related traits with risk of prostate cancer overall, aggressive and early onset disease using outcome summary statistics from the PRACTICAL consortium (including 15,167 aggressive cases). Results: In inverse‐variance weighted models, there was little evidence that genetically predicted one standard deviation higher UFA, FA and BMI were associated with aggressive prostate cancer [OR: 0.85 (95% CI:0.61–1.19), 0.80 (0.53–1.23) and 0.97 (0.88–1.08), respectively]; these associations were largely consistent in sensitivity analyses accounting for horizontal pleiotropy. There was no strong evidence that genetically determined UFA, FA or BMI were associated with overall prostate cancer or early age of onset prostate cancer. Conclusions: We did not find differences in the associations of UFA and FA with prostate cancer risk, which suggest that adiposity is unlikely to influence prostate cancer via the metabolic factors assessed; however, these did not cover some aspects related to metabolic health that may link obesity with aggressive prostate cancer, which should be explored in future studies. [ABSTRACT FROM AUTHOR]

Simple Summary: International standards recommend booster immunization against SARS-CoV-2 in advanced cancer patients undergoing active treatment. Little is known about the relationship between cell-mediated immune responses after vaccination and disease outcomes on immune checkpoint blockade. In this study, we sought to investigate the effects of the third dose of tozinameran on dynamic changes in absolute peripheral lymphocyte counts and their impact on the survival of patients receiving anti-PD-1/PD-L1 agents. The booster dose induced a significant increase in NK cell counts, which correlated with an improved antibody response and a decreased rate of breakthrough infections. Patients with higher levels of NK cells after the third immunization also had a significantly reduced risk of treatment failure in the following six months and longer overall survival. The results from this study provide evidence that COVID-19 vaccination is unlikely to blunt the clinical efficacy of immune checkpoint inhibitors. Our findings also suggest a favorable interaction mediated by the NK cell response, which is consistent with previous insights and needs further confirmation. Background: Anti-SARS-CoV-2 mRNA vaccines can deeply affect cell-mediated immune responses in immunocompromised recipients, including cancer patients receiving active treatments. The clinical implications of changes in peripheral blood lymphocyte subsets following the third dose of mRNA-BNT162b2 vaccination (tozinameran) in patients on immune checkpoint blockade are not fully understood. We conducted a prospective analysis of the Vax-On-Third-Profile study to evaluate the impact of circulating lymphocyte dynamics on disease outcomes in this subgroup of patients. Methods: Recipients of booster dosing who had received before vaccination at least one course of an anti-PD-1/PD-L1 treatment for an advanced solid tumor were eligible. Immunophenotyping of peripheral blood was performed before the third dose of tozinameran (timepoint-1) and four weeks later (timepoint-2) to quantify the absolute counts of lymphocyte subpopulations, including CD3+CD4+ T cells, CD3+CD8+ T cells, B cells, and NK cells. Logistic regression was used to analyze the relationship between lymphocyte subsets and durable clinical benefit (DCB). The log-rank test and Cox regression model were applied to evaluate the relationship between lymphocyte subpopulations and both vaccine-related time-to-treatment failure (V-TTF) and overall survival (OS). Results: We included a total of 56 patients with metastatic disease who were given a third dose of tozinameran between 23 September and 7 October 2021 (median age: 66 years; male: 71%). Most recipients had a diagnosis of lung cancer and were being treated with pembrolizumab or nivolumab. Compared to baseline, the third immunization resulted in an incremental change in the median counts of all lymphocyte subpopulations, which was statistically significant only for NK cells (p < 0.001). A significant correlation was found between NK cell counts and DCB at timepoint-2 (p < 0.001). Multivariate logistic regression analysis of DCB confirmed the predictive significance of high-level NK cell counts (p = 0.020). In multivariate Cox regression analysis, high-level NK cell counts independently predicted longer V-TTF [HR 0.34 (95% CI 0.14–0.80), p = 0.014] and OS [HR 0.36 (95% CI 0.15–0.89), p = 0.027]. Conclusions: Our data suggest expansion of NK cell counts as the most noteworthy change in circulating lymphocytes after the third dose of tozinameran in cancer patients receiving PD-1/PD-L1-targeted agents. This change correlated with enhanced therapeutic efficacy, improving the rate of disease control, and prolonging survival outcomes. Similar findings have not been previously reported, implying that they have proof-of-concept value and warrant further confirmation. [ABSTRACT FROM AUTHOR]

Purpose: Systemic-inflammatory response parameters (SIR) are known prognostic markers in different tumour entities, but have not been evaluated in patients with iCCA treated with systemic chemotherapy. Therefore, we evaluated the impact of different SIR markers on the clinical course of patients with advanced iCCA treated at our center. Methods: SIR markers were retrospectively evaluated in 219 patients with iCCA at the West-German-Cancer-Center Essen from 2014 to 2019. Markers included neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), CRP, and the modified Glasgow-Prognostic-Score (mGPS), which were correlated with clinico-pathological findings, response to chemotherapy (ORR), progression-free (PFS) and overall survival (OS) using Kaplan–Meier analyses, and Cox proportional models. Results: Median overall survival (OS) of the entire cohort was 14.8 months (95% CI 11.2–24.4). Median disease-free survival (DFS) in 81 patients undergoing resection was 12.3 months (95% CI 9.7–23.1). The median OS from start of palliative CTX (OSpall) was 10.9 months (95% 9.4–14.6). A combined Systemic Inflammatory Score (SIS) comprising all evaluated SIR markers correlated significantly with ORR, PFS, and OSpall. Patients with a high SIS (≥ 2) vs. SIS 0 had a significantly inferior OSpall (HR 8.7 95% CI 3.71–20.38, p < 0.001). Multivariate analysis including known prognostic markers (ECOG, CA19-9, LDH, and N- and M-status) identified the SIS as an independent prognostic factor. Conclusions: Inflammatory markers associate with inferior survival outcomes in patients with iCCA. A simple SIS may guide treatment decisions in patients treated with systemic chemotherapy. [ABSTRACT FROM AUTHOR]

J Clin Exp Hepatol 2012; 2 (02): 145-155 60 Vali Y, Lee J, Boursier J LITMUS Systematic Review Team(†) Enhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: a systematic review and meta-analysis. [7] Although most patients with NAFLD do not experience progressive liver disease, some will develop advanced fibrosis, cirrhosis, and liver cancer leading to an increased number of patients being listed for liver transplantation and increased liver mortality. Keywords: nonalcoholic fatty liver disease; risk stratification; advanced disease; noninvasive tests; primary care EN nonalcoholic fatty liver disease risk stratification advanced disease noninvasive tests primary care 142 148 7 07/18/23 20230501 NES 230501 Nonalcoholic fatty liver disease (NAFLD) affects over a third of the world population. [Extracted from the article]

(1) Background: The clinical implications of COVID-19 outbreaks following SARS-CoV-2 vaccination in immunocompromised recipients are a worldwide concern. Cancer patients on active treatment remain at an increased risk of developing breakthrough infections because of waning immunity and the emergence of SARS-CoV-2 variants. There is a paucity of data on the effects of COVID-19 outbreaks on long-term survival outcomes in this population. (2) Methods: We enrolled 230 cancer patients who were on active treatment for advanced disease and had received booster dosing of an mRNA-BNT162b2 vaccine as part of the Vax-On-Third trial between September 2021 and October 2021. Four weeks after the third immunization, IgG antibodies against the spike receptor domain of SARS-CoV-2 were tested in all patients. We prospectively evaluated the incidence of breakthrough infections and disease outcomes. The coprimary endpoints were the effects of antibody titers on the development of breakthrough infections and the impact of COVID-19 outbreaks on cancer treatment failure. (3) Results: At a median follow-up of 16.3 months (95% CI 14.5–17.0), 85 (37%) patients developed SARS-CoV-2 infection. Hospitalization was required in 11 patients (12.9%) and only 2 (2.3%) deaths related to COVID-19 outbreaks were observed. Median antibody titers were significantly lower in breakthrough cases than in non-cases (291 BAU/mL (95% CI 210–505) vs. 2798 BAU/mL (95% CI 2323–3613), p < 0.001). A serological titer cut-off below 803 BAU/mL was predictive of breakthrough infection. In multivariate testing, antibody titers and cytotoxic chemotherapy were independently associated with an increased risk of outbreaks. Time-to-treatment failure after booster dosing was significantly shorter in patients who contracted SARS-CoV-2 infection (3.1 months (95% CI 2.3–3.6) vs. 16.2 months (95% CI 14.3–17.0), p < 0.001) and had an antibody level below the cut-off (3.6 months (95% CI 3.0–4.5) vs. 14.6 months (95% CI 11.9–16.3), p < 0.001). A multivariate Cox regression model confirmed that both covariates independently had a worsening effect on time-to-treatment failure. (4) Conclusions: These data support the role of vaccine boosters in preventing the incidence and severity of COVID-19 outbreaks. Enhanced humoral immunity after the third vaccination significantly correlates with protection against breakthrough infections. Strategies aimed at restraining SARS-CoV-2 transmission in advanced cancer patients undergoing active treatment should be prioritized to mitigate the impact on disease outcomes. [ABSTRACT FROM AUTHOR]

Whilst risk prediction for individual prostate cancer (PCa) cases is of a high priority, the current risk stratification indices for PCa management have severe limitations. This study aimed to identify gene copy number alterations (CNAs) with prognostic values and to determine if any combination of gene CNAs could have risk stratification potentials. Clinical and genomic data of 500 PCa cases from the Cancer Genome Atlas stable were retrieved from the Genomic Data Commons and cBioPortal databases. The CNA statuses of a total of 52 genetic markers, including 21 novel markers and 31 previously identified potential prognostic markers, were tested for prognostic significance. The CNA statuses of a total of 51/52 genetic markers were significantly associated with advanced disease at an odds ratio threshold of ≥1.5 or ≤0.667. Moreover, a Kaplan–Meier test identified 27/52 marker CNAs which correlated with disease progression. A Cox Regression analysis showed that the amplification of MIR602 and deletions of MIR602, ZNF267, MROH1, PARP8, and HCN1 correlated with a progression-free survival independent of the disease stage and Gleason prognostic group grade. Furthermore, a binary logistic regression analysis identified twenty-two panels of markers with risk stratification potentials. The best model of 7/52 genetic CNAs, which included the SPOP alteration, SPP1 alteration, CCND1 amplification, PTEN deletion, CDKN1B deletion, PARP8 deletion, and NKX3.1 deletion, stratified the PCa cases into a localised and advanced disease with an accuracy of 70.0%, sensitivity of 85.4%, specificity of 44.9%, positive predictive value of 71.67%, and negative predictive value of 65.35%. This study validated prognostic gene level CNAs identified in previous studies, as well as identified new genetic markers with CNAs that could potentially impact risk stratification in PCa. [ABSTRACT FROM AUTHOR]

Pancreatic adenosquamous carcinoma (PASC) account for <5% of pancreatic malignancies. The efficacy of modern chemotherapy regimens in patients with advanced PASC is unknown. Patients with advanced PASC from 2008 to 2021 were consecutively included in this retrospective multicenter study. Overall survival (OS) and progression‐free survival (PFS) were evaluated by Kaplan‐Meier method. Ninety‐four PASC from 16 French centers were included (median age, 67.3 years; males, 56.4%; metastatic disease, 85.1%). The first‐line treatment was chemotherapy for 79 patients (84.0%) (37 FOLFIRINOX (FX), 7 Gemcitabine‐nab paclitaxel (GN) and 35 for all other regimen) or best supportive care (BSC) alone for 15 patients (16.0%). No significant difference was observed between FX and GN in terms of PFS (P =.67) or OS (P =.5). Modern regimens pooled together (FX and GN) as compared to all others chemotherapy regimens showed an improvement of overall response rate (39.5% and 9.7%, P =.002), PFS (median, 7.8 vs 4.7 months, P =.02) and OS (median, 12.7 vs 9.2 months, P =.35). This large study evaluating first‐line treatment regimens in advanced PASC suggests that modern regimens as FX or GN may be preferable to all other chemotherapy regimens. These results deserve confirmation in prospective studies. What's new? Pancreatic adenosquamous carcinoma (PASC) is a rare pancreatic cancer subtype of uncertain histological origin. Owing to its scarcity, little is known about the efficacy of chemotherapy for PASC, particularly for advanced disease. Here, investigation of modern chemotherapy regimens in a large multicenter cohort consisting of patients with advanced PASC suggests that more recent regimens based on 5‐fluorouracil, particularly FOLFIRINOX (FX), as well as regimens based on gemcitabine, namely gemcitabine‐nab paclitaxel (GN), are more effective for advanced PASC compared to more conventional regimens. Notably, overall response rates and survival rates were improved in advanced PASC patients on FX and GN regimens. [ABSTRACT FROM AUTHOR]

Background: Advance care planning (ACP) is the process supporting individuals with life-limiting illness to make informed decisions about their future healthcare. Ethnic disparities in ACP have been widely highlighted, but interpretation is challenging due to methodological heterogeneity. This review aims to examine differences in the presence of documented ACP in individuals' care records for people with advanced disease by ethnic group, and identify patient and clinician related factors contributing to this. Methods: Mixed-methods systematic review. Keyword searches on six electronic databases were conducted (01/2000–04/2022). The primary outcome measure was statistically significant differences in the presence of ACP in patients' care records by ethnicity: quantitative data was summarised and tabulated. The secondary outcome measures were patient and clinician-based factors affecting ACP. Data was analysed qualitatively through thematic analysis; themes were developed and presented in a narrative synthesis. Feedback on themes was gained from Patient and Public Involvement (PPI) representatives. Study quality was assessed through Joanna Briggs Institute Critical Appraisal tools and Gough's Weight of Evidence. Results: N=35 papers were included in total; all had Medium/High Weight of Evidence. Fifteen papers (comparing two or more ethnic groups) addressed the primary outcome measure. Twelve of the fifteen papers reported White patients had statistically higher rates of formally documented ACP in their care records than patients from other ethnic groups. There were no significant differences in the presence of informal ACP between ethnic groups. Nineteen papers addressed the secondary outcome measure; thirteen discussed patient-based factors impacting ACP presence with four key themes: poor awareness and understanding of ACP; financial constraints; faith and religion; and family involvement. Eight papers discussed clinician-based factors with three key themes: poor clinician confidence around cultural values and ideals; exacerbation of institutional constraints; and pre-conceived ideas of patients' wishes. Conclusions: This review found differences in the presence of legal ACP across ethnic groups despite similar presence of informal end of life conversations. Factors including low clinician confidence to deliver culturally sensitive, individualised conversations around ACP, and patients reasons for not wishing to engage in ACP (including, faith, religion or family preferences) may begin to explain some documented differences. Trial registration: PROSPERO-CRD42022315252. [ABSTRACT FROM AUTHOR]

Abstract Background African ancestry is a significant risk factor for advanced prostate cancer (PCa). Mortality rates in sub-Saharan Africa are 2.5-fold greater than global averages. However, the region has largely been excluded from the benefits of whole genome interrogation studies. Additionally, while structural variation (SV) is highly prevalent, PCa genomic studies are still biased towards small variant interrogation. Methods Using whole genome sequencing and best practice workflows, we performed a comprehensive analysis of SVs for 180 (predominantly Gleason score ≥ 8) prostate tumours derived from 115 African, 61 European and four ancestrally admixed patients. We investigated the landscape and relationship of somatic SVs in driving ethnic disparity (African versus European), with a focus on African men from southern Africa. Results Duplication events showed the greatest ethnic disparity, with a 1.6- (relative frequency) to 2.5-fold (count) increase in African-derived tumours. Furthermore, we found duplication events to be associated with CDK12 inactivation and MYC copy number gain, and deletion events associated with SPOP mutation. Overall, African-derived tumours were 2-fold more likely to present with a hyper-SV subtype. In addition to hyper-duplication and deletion subtypes, we describe a new hyper-translocation subtype. While we confirm a lower TMPRSS2-ERG fusion-positive rate in tumours from African cases (10% versus 33%), novel African-specific PCa ETS family member and TMPRSS2 fusion partners were identified, including LINC01525, FBXO7, GTF3C2, NTNG1 and YPEL5. Notably, we found 74 somatic SV hotspots impacting 18 new candidate driver genes, with CADM2, LSAMP, PTPRD, PDE4D and PACRG having therapeutic implications for African patients. Conclusions In this first African-inclusive SV study for high-risk PCa, we demonstrate the power of SV interrogation for the identification of novel subtypes, oncogenic drivers and therapeutic targets. Identifying a novel spectrum of SVs in tumours derived from African patients provides a mechanism that may contribute, at least in part, to the observed ethnic disparity in advanced PCa presentation in men of African ancestry.

Background: Racial disparities in pain management have been observed in the USA since the 1990s in settings such as the emergency department and oncology. However, the palliative care context is not well described, and little research has focused outside of the USA or on advanced disease. This review takes a cross-national approach to exploring pain management in advanced disease for people of different racial and ethnic groups. Methods: Mixed methods systematic review. The primary outcome measure was differences in receiving pain medication between people from different racial and ethnic groups. Five electronic databases were searched. Two researchers independently assessed quality using JBI checklists, weighted evidence, and extracted data. The quantitative findings on the primary outcome measure were cross-tabulated, and a thematic analysis was undertaken on the mixed methods studies. Themes were formulated into a conceptual/thematic matrix. Patient representatives from UK ethnically diverse groups were consulted. PRISMA 2020 guidelines were followed. Results: Eighteen papers were included in the primary outcome analysis. Three papers were rated ‘High’ weight of evidence, and 17/18 (94%) were based in the USA. Ten of the eighteen (56%) found no significant difference in the pain medication received between people of different ethnic groups. Forty-six papers were included in the mixed methods synthesis; 41/46 (89%) were based in the USA. Key themes: Patients from different ethnically diverse groups had concerns about tolerance, addiction and side effects. The evidence also showed: cultural and social doctor-patient communication issues; many patients with unmet pain management needs; differences in pain assessment by racial group, and two studies found racial and ethnic stereotyping. Conclusions: There was not enough high quality evidence to draw a conclusion on differences in receiving pain medication for people with advanced disease from different racial and ethnic groups. The mixed methods findings showed commonalities in fears about pain medication side effects, tolerance and addiction across diverse ethnic groups. However, these fears may have different foundations and are differently prioritised according to culture, faith, educational and social factors. There is a need to develop culturally competent pain management to address doctor-patient communication issues and patients’ pain management concerns. Trial registration: PROSPERO-. [ABSTRACT FROM AUTHOR]

Prostate cancer is the second most common cause of death in men worldwide, after lung carcinoma. Although early treatment and preventive medicine practices came to the fore in the era of PSA followup, and subsequent needle biopsies made it easier to detect the tumor development of the patients, but we did not have much chance in terms of determining the behavior of the tumor especially before, during and after the treatment, except for risk scoring schemes. Today, the molecular signature and molecular biology of the disease, which we can use to determine individual treatment models and to predict the prognosis of the disease, are important. For all these reasons, medical professional's knowledge of the molecular pathogenesis and biological attitude of prostate cancer will help to understand the disease and its course. [ABSTRACT FROM AUTHOR]

Abstract Background Racial disparities in pain management have been observed in the USA since the 1990s in settings such as the emergency department and oncology. However, the palliative care context is not well described, and little research has focused outside of the USA or on advanced disease. This review takes a cross-national approach to exploring pain management in advanced disease for people of different racial and ethnic groups. Methods Mixed methods systematic review. The primary outcome measure was differences in receiving pain medication between people from different racial and ethnic groups. Five electronic databases were searched. Two researchers independently assessed quality using JBI checklists, weighted evidence, and extracted data. The quantitative findings on the primary outcome measure were cross-tabulated, and a thematic analysis was undertaken on the mixed methods studies. Themes were formulated into a conceptual/thematic matrix. Patient representatives from UK ethnically diverse groups were consulted. PRISMA 2020 guidelines were followed. Results Eighteen papers were included in the primary outcome analysis. Three papers were rated ‘High’ weight of evidence, and 17/18 (94%) were based in the USA. Ten of the eighteen (56%) found no significant difference in the pain medication received between people of different ethnic groups. Forty-six papers were included in the mixed methods synthesis; 41/46 (89%) were based in the USA. Key themes: Patients from different ethnically diverse groups had concerns about tolerance, addiction and side effects. The evidence also showed: cultural and social doctor-patient communication issues; many patients with unmet pain management needs; differences in pain assessment by racial group, and two studies found racial and ethnic stereotyping. Conclusions There was not enough high quality evidence to draw a conclusion on differences in receiving pain medication for people with advanced disease from different racial and ethnic groups. The mixed methods findings showed commonalities in fears about pain medication side effects, tolerance and addiction across diverse ethnic groups. However, these fears may have different foundations and are differently prioritised according to culture, faith, educational and social factors. There is a need to develop culturally competent pain management to address doctor-patient communication issues and patients’ pain management concerns. Trial registration PROSPERO- CRD42020167890 .

Objectives Colorectal cancer (CRC) is the second leading cause of cancer death in the world, with survival correlated with the extension of the disease at diagnosis. In many low-/middle-income countries, the incidence of CRC is increasing rapidly, while decreasing rates are observed in high-income countries. We evaluated the anatomopathological profile of 390 patients diagnosed with CRC who underwent surgical resection, over a six-year period, in the state of Paraíba, northeastern Brazil. Results Adenocarcinomas accounted for 98% of the cases of primary colorectal tumors, and 53.8% occurred in female patients. The average age of the sample was 63.5 years, with 81.8% of individuals older than 50 years of age and 6.4% under 40 years of age. The most frequent location was the distal colon; pT3 status was found in 71% of patients, and pT4 status, in 14.4%. Angiolymphatic and lymph-node involvements were found in 48.7% and 46.9% of the cases respectively. Distant metastasis was observed in 9.2% of the patients. Advanced disease was diagnosed in almost half of the patients (48.1%). The women in the sample had poorly-differentiated adenocarcinomas (p = 0.043). Patients under 60 years of age had a higher rate of lymph-node metastasis (p = 0.044). Tumor budding was present in 27.2% of the cases, and it was associated with the female gender, the mucinous histological type, and the depth of invasion (pT3 and pT4). Conclusions We conclude that the diagnosis of advanced disease in CRC is still a reality, with a high occurrence of aggressive prognostic factors, which results in a worse prognosis.

The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a global multicenter retrospective analysis of its first-line treatment outcomes. We included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab, gemcitabine, and cisplatin at 39 sites in 11 countries (Europe, the United States, and Asia). The primary endpoint was overall survival (OS). 666 patients were enrolled. Median OS was 15.1 months and median PFS was 8.2 months. The investigator-assessed overall response rate was 32.7 %, with stable disease in 45.2 % of patients. High baseline CEA levels, ECOG PS > 0, metastatic disease, and NLR > 3 were associated with poor survival. Any grade adverse events (AEs) occurred in 92.9 % of patients (grade >2: 46.6 %). Immune-related AEs (irAEs) occurred in 20.0 % (grade >2: 2.5 %). Three deaths (0.5 %) were deemed treatment-related, none linked to immunotherapy. Common irAEs were rash (8.2 % all grades; 0.3 % grade >2), itching (10.3 % all grades; 0.2 % grade >2), and hypothyroidism (5.1 % all grades; 0.3 % grade >2). Durvalumab discontinuation rate due to AEs was 1.5 %. ESMO-recommended genes were analyzed and no outcome differences were found. A comparative analysis with a historical cohort of patients treated with chemotherapy alone confirmed the positive survival impact of durvalumab in combination with cisplatin/gemcitabine. This first global real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC. • Real-world evidence is gaining momentum in clinical oncology in recent years. • Durvalumab improved survival in patients with advanced biliary tract cancer. • 666 patients were treated: median OS of 15.1 months and median PFS of 8.2 months. • The results confirmed the results achieved in the TOPAZ-1 trial. [ABSTRACT FROM AUTHOR]

[Display omitted] • The therapeutic options for patients with advanced/recurrent EC were limited. • The sequencing and molecular classification by TCGA has revolutionized therapeutic management of endometrial cancer. • The emergence of targeted therapies and immunotherapy represents significant progress. • Several promising therapies: immunotherapy for MMRd, selinexor for p53wt and trastuzumab deruxtecan for high levels of HER2. Until recently, patients diagnosed with locally advanced and metastatic endometrial cancer faced significant challenges in their treatment due to limited options and poor prognostic outcomes. The sequencing of tumors has been a major advancement in its management. It has led to The Cancer Genome Atlas classification currently used in clinical practice and the initiation of several clinical trials for innovative treatments targeting principally signaling pathways, immune checkpoints, DNA integrity, growth factors, hormonal signaling, and metabolism. Numerous clinical trials are investigating a combinatorial approach of these targeted therapies to counter tumoral resistance, cellular compensatory mechanisms, and tumor polyclonality. This review provides a comprehensive overview of historical, current, and promising therapies in advanced and metastatic endometrial cancer. It particularly highlights clinical research on targeted and hormonal therapies, but also immunotherapy, reflecting the evolving landscape of treatment modalities for this disease. [ABSTRACT FROM AUTHOR]

Background: Our aim was to explore relevance of the proportion between neoplastic cell component and tumor-associated stroma in order to assess its association with confirmed aggressive phenotypes of right/left colon and rectum cancers in a large series of patients. Methods: The quantification of stroma component was performed in patients diagnosed with colorectal adenocarcinoma who underwent surgical resection. The analyzed variables were age, gender, anatomical/pathological features, and tumor-stroma proportion. Tumor-stroma proportion was estimated based on slides used in routine pathology for determination of T status and was described as low, with a stromal percentage ≤50% or high, with a stromal percentage >50%. The tumor-stroma proportion was estimated by two observers, and the inter-observer agreement was assessed. Results: The sample included 390 colorectal adenocarcinoma patients. Stroma-rich tumors were observed in 53.3% of cases. Well-differentiated tumors had the lowest stromal proportions (p = 0.028). Stroma-poor tumors showed less depth of invasion (p

BackgroundHead and neck mucosal melanoma (HNMM) is a rare and aggressive subtype of melanoma. HNMM often develops as a recurrent or metastatic disease, and its prognosis is worse than that of cutaneous melanoma. Recent large-scale clinical studies have reported favorable outcomes with immune checkpoint inhibitors (ICIs) for melanoma. However, these clinical trials included only a small number of HNMM cases. This study aimed to estimate treatment outcomes and prognostic predictors of ICIs for advanced HNMM.MethodsCases of advanced HNMM, defined as unresectable or metastatic HNMM at the initial diagnosis (five patients) or development of recurrent/metastatic HNMM after initial treatment (27 patients), were included in this study. Survival analysis and a search for prognostic factors were performed for these 32 patients. Furthermore, the detailed clinical course of patients who received ICI treatment was investigated.ResultsThe median overall survival (OS) of 32 patients with advanced HNMM was 25.3 months. The estimated 1-, 3-, and 5-year OS rates were 68.4%, 42.8%, and 34.3%, respectively. Fourteen patients (43.7%) received ICIs, whereas 18 (56.3%) did not. Univariate analysis showed that ICI treatment was the only factor associated with a better 1-year OS. Patients who received ICI treatment had significantly longer OS (median OS: not reached, 1-year OS: 85.7%) than those who did not (median OS: 11.3 months, 1-year OS: 54.5%). The overall response and disease control rates of patients who received ICI treatment were 50% and 64.3%, respectively. Patients who achieved complete response (CR) or partial response (PR) to ICI treatment survived significantly longer (1-year OS: 100%) than those who did not (1-year OS: 71.4%). Among the five patients who discontinued ICI treatment due to severe immune-related adverse events (irAEs), four did not receive salvage treatments but showed durable treatment effects and survived for 9.8–54.2 months at the end of the follow-up period.ConclusionsICI treatment achieved a favorable OS for advanced HNMM. CR/PR to ICI treatment and discontinuation owing to severe irAEs were favorable predictors of OS.

OBJECTIVE Regorafenib, a multikinase inhibitor, is an approved third-line therapy for advanced gastrointestinal stromal tumors (GISTs). However, its routine clinical application is difficult due to the associated adverse events (AEs) reported by patients in the 1st month, which leads to early discontinuation. In this study, we presented our experiences in toxicities management and the effectiveness of regorafenib in our institutional cancer center. METHODS Twenty-two patients treated with regorafenib as a third-line therapy for advanced GISTs were retrospectively evaluated who had progressive disease after imatinib and sunitinib treatments. All patients received a full dose of 160 mg/day of regorafenib. RESULTS The average age of the patients was 49 years (range: 25-61 years), with a male preponderance (63.6%). The average follow-up time for the subjects was 114.2 months (16.2-210.3), while the median time of regorafenib using time was 7.7 months (1.9-29.1). The median overall survival (OS) of the patients was found as 10 months, while the 1-year OS rate was 38.3%. The median progression-free survival was found as 7.1 months. Regorafenib-related partial response was observed in 5 patients (22.7%), stable disease in 9 (40.9%), and progressive disease in 8 (36.4%). The disease control rate was 63.7%. Treatment- related grade 3/4 AEs were seen in ten (45.4%) patients. The most common AE was hand-foot skin reaction (5; 18.2%), followed by fatigue (3; 13.6%) and hypertension (2; 9.1%). Dose reductions were required in 7 patients (31.8%). The treatment was discontinued in a patient due to stroke. CONCLUSION Our results demonstrate promising activity and manageable side effects of regorafenib as third-line therapy of GIST in daily clinical practice in the Turkish population. [ABSTRACT FROM AUTHOR]

Purpose: Advances in treatment, including biological and precision therapies, mean that more people are living with advanced cancer. Supportive care needs likely change across the cancer journey. We systematically identified instruments available to assess unmet needs of advanced cancer patients and evaluated their development, content, and quality. Methods: Systematic searches of MEDLINE, CINAHL, Embase, PubMed, and PsycINFO were performed from inception to 11 January 2021. Independent reviewers screened for eligibility. Data was abstracted on instrument characteristics, development, and content. Quality appraisal included methodological and quality assessment, GRADE, feasibility, and interpretability, following consensus-based standards for the selection of health measurement instruments (COSMIN) guidelines. Results: Thirty studies reporting 24 instruments were identified. These were developed for general palliative patients (n = 2 instruments), advanced cancer (n = 8), and cancer irrespective of stage (n = 14). None focused on patients using biological or precision therapies. The most common item generation and reduction techniques were amending an existing instrument (n = 11 instruments) and factor analysis (n = 8), respectively. All instruments mapped to ≥ 5 of 11 unmet need dimensions, with Problems and Needs in Palliative Care (PNPC) and Psychosocial Needs Inventory (PNI) covering all 11. No instrument reported all of the COSMIN measurement properties, and methodological quality was variable. Conclusions: Many instruments are available to assess unmet needs in advanced cancer. There is extensive heterogeneity in their development, content, and quality. Implications for Cancer Survivors: Given the growth of precision and biological therapies, research needs to explore how these instruments perform in capturing the needs of people using such therapies. [ABSTRACT FROM AUTHOR]

Background: In the TOPAZ-1, patients with biliary tract cancers (BTC) and recurrence within 6 months after surgery were excluded, even if this event is frequently observed in clinical practice. Our study aimed to assess if the efficacy of cisplatin-gemcitabine-durvalumab (CGD) in this population is comparable to that reported in the phase 3 trial., Methods: The study cohort included patients with BTC who underwent surgery on the primary tumor, experienced disease recurrence occurring ≤6 months or >6 months after surgery or after the end of adjuvant therapy and started CGD. The primary objectives were overall survival (OS) and progression free survival (PFS)., Results: A total of 178 patients were enrolled. No significant differences were observed between early and late relapse groups in OS (23.4 months vs not reached; HR 1.26; 95% CI, 0.67-2.37; P = .45) and PFS [7.0 months vs 9.8 months; HR 1.3(95% CI, 0.9-2.1) P = .13]. Overall response rate and disease control rate (P = .33 and P = .62) were comparable between the 2 groups, as the overall safety profile. In addition, we compared survival outcomes between the selected population and a historical cohort of patients with BTC treated with cisplatin-gemcitabine (CG) and found that despite the absence of statistical significance, CGD showed an outcome trend compared with CG regardless of the time of recurrence after surgery or adjuvant chemotherapy [(CG ≤ 6 vs CGD ≤ 6 months: HR 0.59, 95%CI, 0.35-1.01, P = .05; HR 0.70; 95%CI, 0.46-1.06, P = .09, OS and PFS, respectively) and (CG > 6 vs. CGD > 6 months: HR 0.50; 95%CI, 0.29-0.88, P = 0.0165; HR 0.54; 95%CI, 0.35-0.84, P = .0068, OS and PFS, respectively)]., Conclusion: Our analysis suggests that CGD retains its efficacy independently of the timing of relapse after surgery or completion of adjuvant treatment in patients with advanced BTC., (© The Author(s) 2024. Published by Oxford University Press.)

The German Hodgkin Study Group developed the escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) protocol as a treatment strategy for advanced-stage Hodgkin's lymphoma. In Brazil, as well as in other countries, procarbazine has been replaced with dacarbazine due to the limited availability of procarbazine. The Hematology Center at Irmandade da Santa Casa de Misericórdia in São Paulo adopted and modified the escalated BEACOPP protocol, substituting prednisone with dexamethasone and incorporating two different doses of dacarbazine: 375 mg/m 2 /day on Day 8 or the original dose of 250 mg/m 2 /day on Days 2 and 3. This adjustment was made in response to the anticipated toxicity profile. This study aimed to compare the two different doses in the protocols (375 mg/m 2 /cycle versus 500 mg/m 2 /cycle) administered to patients with advanced Hodgkin's lymphoma in similar periods. This retrospective study analyzed the data of 31 patients at a single center in Brazil from 2019 to 2021. Seventeen of the 31 patients received 500 mg/m 2 /cycle (500 Group), while 14 received 375 mg/m 2 /cycle (375 Group). At the end of the protocol, 71% of the patients in the 375 Group and 76% in the 500 Group achieved complete remission. On analyzing the number of cycles that patients presented with febrile neutropenia, the 500 Group had three times more events (17.9%) than the 375 Group (6.09% - p-value = 0.04). In the 500 Group, 47.1% needed to change the protocol to ABVD (doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine) due to toxicity. In this limited cohort from a single public center in Brazil, the use of 375 mg/m 2 of dacarbazine per cycle of the modified escalated BEACOPP protocol emerged as a safer strategy, maintaining treatment efficacy without compromising response in patients with advanced Hodgkin's lymphoma., Competing Interests: Conflicts of interest The authors declare no conflicts of interest, (Copyright © 2024 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Background: To present findings from a retrospective study conducted by the Ultra-Rare Sarcoma Working Group on metastatic low-grade fibromyxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), and hybrid (H)-LGFMS/SEF across 28 global centres., Methods: Patients treated at participating institutions from January 2000 to September 2022 were retrospectively selected. Diagnosis was confirmed by expert pathologists. Primary endpoint was progression-free survival (PFS-1) from metastasis detection to first progression or death. PFS-2 was calculated from therapy initiation., Results: A total of 101 patients were identified (32 LGFMS, 50 SEF, 19 H-LGFMS/SEF). Median (m) follow-up was 62.1 months. mPFS-1 was 28.7, 11.8, and 20.3 months for LGFMS, SEF, and H-LGFMS/SEF, respectively. mOS was 145.8, 41.9, and 113.5 months, respectively. Treatments included anthracycline-based chemotherapy, gemcitabine-based chemotherapy (G), pazopanib, trabectedin, others. mPFS-2 was: 20.1, 5.5, and 3.5 months in H-LGFMS/SEF, SEF, and LGFMS, respectively, with anthracyclines; 19.5, 7.7, and 6.9 months in LGFMS, SEF, and H-LGFMS/SEF, respectively, with pazopanib; 12.0, 9.7, and 3.1 months in H-LGFMS/SEF, LGFMS, and SEF, respectively. Occasional responses occurred with ifosfamide/oral cyclophosphamide, and prolonged stable disease with immune checkpoint inhibitors., Conclusions: In this series, the largest available, metastatic LGFMS, SEF, and H-LGFMS/SEF showed different courses. Systemic agents have modest efficacy, informing future trials of novel agents for these tumours., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: African ancestry is a significant risk factor for advanced prostate cancer (PCa). Mortality rates in sub-Saharan Africa are 2.5-fold greater than global averages. However, the region has largely been excluded from the benefits of whole genome interrogation studies. Additionally, while structural variation (SV) is highly prevalent, PCa genomic studies are still biased towards small variant interrogation. Methods: Using whole genome sequencing and best practice workflows, we performed a comprehensive analysis of SVs for 180 (predominantly Gleason score ≥ 8) prostate tumours derived from 115 African, 61 European and four ancestrally admixed patients. We investigated the landscape and relationship of somatic SVs in driving ethnic disparity (African versus European), with a focus on African men from southern Africa. Results: Duplication events showed the greatest ethnic disparity, with a 1.6- (relative frequency) to 2.5-fold (count) increase in African-derived tumours. Furthermore, we found duplication events to be associated with CDK12 inactivation and MYC copy number gain, and deletion events associated with SPOP mutation. Overall, African-derived tumours were 2-fold more likely to present with a hyper-SV subtype. In addition to hyper-duplication and deletion subtypes, we describe a new hyper-translocation subtype. While we confirm a lower TMPRSS2-ERG fusion-positive rate in tumours from African cases (10% versus 33%), novel African-specific PCa ETS family member and TMPRSS2 fusion partners were identified, including LINC01525, FBXO7, GTF3C2, NTNG1 and YPEL5. Notably, we found 74 somatic SV hotspots impacting 18 new candidate driver genes, with CADM2, LSAMP, PTPRD, PDE4D and PACRG having therapeutic implications for African patients. Conclusions: In this first African-inclusive SV study for high-risk PCa, we demonstrate the power of SV interrogation for the identification of novel subtypes, oncogenic drivers and therapeutic targets. Identifying a novel spectrum of SVs in tumours derived from African patients provides a mechanism that may contribute, at least in part, to the observed ethnic disparity in advanced PCa presentation in men of African ancestry. [ABSTRACT FROM AUTHOR]

This study aimed at investigating nurse practitioners' self-efficacy and behavior in supporting self-management of patients with a progressive, life-threatening illness and their relatives. We adapted an existing validated instrument for this purpose, amongst other things by adding a seventh subscale "attention for relatives," and administered it in a nationwide, cross-sectional online survey among Dutch nurse practitioners. We analyzed associations between self-reported self-efficacy and behavior using Pearson correlations and paired sample t tests. Associations between self-efficacy and behavior with nurse practitioners' characteristics were examined using linear regression models. Most nurse practitioners (n = 327; 26% complete responses) were women (93%). Subscale and total scores for nurse practitioners' self-efficacy were moderately positively correlated with those for their behavior in self-management support. Subscale and total scores were statistically significantly higher for their self-efficacy than for their behavior. Increased work experience with patients with a progressive, life-threatening illness was associated with higher scores on self-efficacy and behavior in self-management support. We conclude that nurse practitioners are confident in their ability to support self-management; yet, they do not always use these competencies in practice. [ABSTRACT FROM AUTHOR]