Advanced Cancer Status Research Articles

Ethical reflections on phase I clinical trials of anticancer drugs: from a Chinese IRB’s empirical perspective

PurposeWith the rapid development of Phase I clinical trials for anticancer drugs in China, addressing ethical concerns is imperative. In order to safeguard the rights, interests, and well-being of research participants, this paper aims to illustrate vital ethical issues that should not be neglected by institutional review boards as well as other relevant stakeholders for Phase I clinical trials of anticancer drugs.MethodsThis study retrospectively collects documents on Phase I clinical trials for anticancer drugs that were submitted to the Institutional Review Board at Zhejiang Cancer Hospital from 2021 to 2023. Based on Chinese and international research regulations and guidelines, these documents, as well as initial and follow-up review resolutions, have been classified and analyzed.ResultsGiven the additional risks of potentially toxic effects in Phase I clinical trials for anticancer drugs and the vulnerability of participants enrolled with advanced cancer status, it is important to review investigator qualifications, preliminary findings, research methods, inclusion and exclusion criteria in the protocol, as well as the validity and readability of informed consent. Additionally, attention should be given to follow-up reviews, particularly regarding safety reports and protocol deviations.ConclusionTo effectively protect the rights, interests and safety of research participants. Relevant stakeholders, including sponsors, researchers, and regulatory bodies, should diligently evaluate potential risks and provision contingency plan to minimize the latent risk.

Non-invasive technology to assess hydration status in advanced cancer to explore relationships between fluid status and symptoms: an observational study using bioelectrical impedance analysis

BackgroundOral fluid intake decreases in advanced cancer in the dying phase of illness. There is inadequate evidence to support the assessment, and management, of hydration in the dying. Bioelectrical impedance analysis (BIA) is a body composition assessment tool. BIA has the potential to inform clinal management in advanced cancer, by examining the relationships between hydration status and clinical variables.AimBIA was used to determine the association between hydration status, symptoms, clinical signs, quality-of-life and survival in advanced cancer, including those who are dying (i.e. in the last week of life).Materials and methodsWe conducted a prospective observational study of people with advanced cancer in three centres. Advance consent methodology was used to conduct hydration assessments in the dying. Total body water was estimated using the BIA Impedance index (Height – H (m)2 /Resistance – R (Ohms)). Backward regression was used to identify factors (physical signs, symptoms, quality of life) that predicted H2/R. Participants in the last 7 days of life were further assessed with BIA to assess hydration changes, and its relationship with clinical outcomes.ResultsOne hundred and twenty-five people participated (males n = 74 (59.2%), females, n = 51 (40.8%)). We used backward regression analysis to describe a statistical model to predict hydration status in advanced cancer. The model demonstrated that ‘less hydration’ (lower H2/R) was associated with female sex (Beta = -0.39, p < 0.001), increased appetite (Beta = -0.12, p = 0.09), increased dehydration assessment scale score (dry mouth, dry axilla, sunken eyes - Beta = -0.19, p = 0.006), and increased breathlessness (Beta = -0.15, p = 0.03). ‘More hydration’ (higher H2/R) was associated with oedema (Beta = 0.49, p < 0.001). In dying participants (n = 18, 14.4%), hydration status (H2/R) was not significantly different compared to their baseline measurements (n = 18, M = 49.6, SD = 16.0 vs. M = 51.0, SD = 12.1; t(17) = 0.64, p = 0.53) and was not significantly associated with agitation (rs = -0.85, p = 0.74), pain (rs = 0.31, p = 0.23) or respiratory tract secretions (rs = -0.34, p = 0.19).ConclusionsThis is the first study to use bioimpedance to report a model (using clinical factors) to predict hydration status in advanced cancer. Our data demonstrates the feasibility of using an advance consent method to conduct research in dying people. This method can potentially improve the evidence base (and hence, quality of care) for the dying. Future BIA research can involve hydration assessment of cancers (according to type and stage) and associated variables (e.g., stage of illness, ethnicity and gender). Further work can use BIA to identify clinically relevant outcomes for hydration studies and establish a core outcome set to evaluate how hydration affects symptoms and quality-of-life in cancer.

Low Pretreatment Albumin-to-Globulin Ratios Predict Poor Survival Outcomes in Patients with Head and Neck Cancer: A Systematic Review and Meta-analysis.

Background: Studies have indicated that a low albumin-to-globulin ratio (AGR) before treatment is linked to poor prognosis of many cancers, but the prognostic impact of AGR remains controversial in head and neck cancer (HNC). This meta-analysis examined the prognostic value of AGR in HNC. Methods: We systematically searched the Embase, PubMed, and Cochrane library for relevant articles from inception to July 22, 2022. Studies conducted from 2000 to 2022 exploring the prognostic value of AGR in HNC were retrieved. We employed a random-effects model and calculated pooled hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) to examine the associations of AGR with survival outcome. Results: Our analysis included nine studies involving 3211 patients with HNC. The pooled results revealed significant associations between low pretreatment AGRs and poor disease-free survival (HR = 1.97, 95% CI 1.58-2.45, p < 0.001), distant metastasis-free survival (HR = 1.64, 95% CI 1.25-2.16, p < 0.001), overall survival (HR = 2.18, 95% CI 1.65-2.88, p < 0.001), T3-T4 status (OR = 2.22, 95% CI 1.43-3.44, p < 0.001), stage III-IV disease (OR = 2.62, 95% CI 1.62-4.23, p < 0.001), and lymph node metastasis (OR = 1.95, 95% CI 1.29-2.82, p = 0.001) in patients with HNC. Conclusion: AGR can serve as a prognostic biomarker in managing HNC, and a low pretreatment AGR is strongly associated with adverse survival outcomes and advanced cancer status. Additional large-scale prospective trials must be conducted to assess the validity of our findings.

Indoleamine 2,3-dioxygenase gene expression and kynurenine to tryptophan ratio correlation with nasopharyngeal carcinoma progression and survival.

IntroductionIndoleamine 2,3‐dioxygenase (IDO) is an immunosuppressive tryptophan‐depleting enzyme expressed in nasopharyngeal carcinoma (NPC) tissue. However, IDO has not been reported in the peripheral blood of NPC patients. The aim of this study was to analyze, IDO1 and IDO2 messenger RNA (mRNA) expression, the kynurenine (Kyn) and tryptophan (Trp) plasma levels, their clinical values and their relationship with cytokine levels in NPC.MethodsWe evaluated IDO1 and IDO2 mRNA expression in peripheral blood mononuclear cells (PBMC) by quantitative real‐time PCR, plasma Trp and Kyn levels by HPLC, and cytokine levels by ELISA in 75 NPC patients and 51 healthy controls.ResultsCompared to controls, IDO1 mRNA expression was significantly upregulated and IDO2 mRNA expression was significantly downregulated in PBMC of patients. Also compared to controls, plasma Kyn levels and Kyn/Trp ratio were significantly higher in patients. At the time of diagnosis, the plasma Kyn/Trp ratio was associated with advanced cancer status and was an independent prognostic factor for worse disease‐specific survival. According to cancer stages, IDO1 mRNA expression was positively correlated with plasma Kyn/Trp ratio in patients with earlier stages (I–II–III) but negatively correlated in patients with the late‐stage cancer (IV). Tumor necrosis factor‐α, interleukin (IL)‐6 and IL‐10 levels were significantly higher in patients compared to controls. Moreover, and despite treatment, patients simultaneously carrying high plasma Kyn/Trp ratio and high plasma IL‐6 and IL‐10 levels at diagnosis died approximately 1 year after first diagnosis.ConclusionMeasuring blood IDO mRNA expression and Kyn/Trp ratio at diagnosis could be a potential marker to evaluate NPC progression and predict survival outcome.

Impact of Palliative Care Interventions on Health-Related Quality of Life (HRQOL): A Secondary Analysis of the Promoting Resilience in Stress Management (PRISM) Randomized Controlled Trial (RCT) (S870)

1.Review the concept of health-related quality of life as a study outcome.2.Evaluate the effectiveness of an intervention using patient-reported health-related quality of life as an outcome. PRISM is a novel resilience-building intervention for adolescents and young adults (AYAs). Primary analysis of the RCT in AYAs with cancer showed PRISM improved HRQOL. Secondary analysis explored changes in HRQOL domains and differences between patient groups. English-speaking AYAs (12-25 years) were randomized to PRISM or usual care (UC) from 1/2015 – 10/2016. Surveys were completed at enrollment and six months later, using the Pediatric Quality of Life Inventory (PedsQL) Generic Short Form (SF-15) and Cancer Module to assess HRQOL. We compared change scores (PRISM vs UC) by domain (PedsQL SF-15: physical, emotional, social, school; Cancer: pain, nausea, procedure anxiety, treatment anxiety, worry, cognition, perceived appearance, communication). Participants were stratified by age (12-17 years vs 18-25 years) and advanced cancer status (yes/no). 74 patients (36 PRISM, 38 UC) completed 6-month assessments. 72% were 12-17 years old. 23% had advanced cancer at enrollment. PRISM improved patient-reported communication (UC: median [interquartile range, IQR] 0 [-17, 8]; PRISM: 8 [0, 25]). Younger patients benefited more, especially in PedsQL SF-15 school (12-17: UC 0 [-8, 0], PRISM 13 [0, 17]; 18-25: UC 0 [-33, 17], PRISM 0 [-25, 17]) and social domains (12-17: UC 0 [-33, 0], PRISM 0 [0, 8]; 18-25: UC 0 [-25, 4], PRISM -17 [-25, 8]), and cancer-specific perceived appearance (12-17: UC -4 [-25, 0], PRISM 8 [-8, 25]; 18-25: UC 0 [-21, 0], PRISM -8 [-25, 17]). Patients with advanced cancer benefited more in cancer-specific domains nausea (no: UC 0 [-10, 15], PRISM 10 [-10, 40]; yes: UC 6 [-15, 25], PRISM 35 [25, 50]) and pain (no: UC 13 [-13, 25], PRISM 6 [-13, 25]; yes: UC -13 [-25, 0], PRISM 6 [-13, 25]). With PRISM, younger AYAs coped better with age-appropriate challenges and AYAs with advanced cancer improved physical symptom HRQOL.

Influence of androgen deprivation therapy on serum urate levels in patients with prostate cancer: A retrospective observational study.

ObjectivesAlthough estrogenic modulation of serum urate levels is well-known, the androgenic effect on urate homeostasis remains controversial. We investigated the effect of androgen deprivation therapy (ADT) on serum urate levels.MethodsWe retrospectively enrolled a total of 489 prostate cancer patients with available serum urate levels at baseline and 3 and 6 months after ADT (n = 150) or prostate surgery (n = 339). We extracted the demographic, clinical, and laboratory data from a data warehouse and compared the changes in urate levels between the two treatment groups and between the different ADT regimens (with versus without luteinizing hormone-releasing hormone (LHRH) agonists) using generalized estimating equation (GEE).ResultsThe baseline urate levels and the proportion of hyperuricemic subjects were comparable between the two groups. After 6 months, the urate levels were significantly decreased (by −0.66 mg/dL, 95% confidence interval (CI) [-0.81 to -0.51]) in the ADT group, whereas they did not significantly change in the surgery group in the univariate GEE analysis. The ADT group (4.7% from 18.0% at baseline) had a significantly lower proportion of hyperuricemic patients than surgery group (16.5% from 15.9% at baseline) at 6-month (p < 0.001). Regardless of whether LHRH agonists were used, the serial urate levels were lowered by the ADT. Temporal changes in the urate levels were significantly associated with the treatment group, baseline hyperuricemia, and poor functional or advanced cancer status. The ADT-related serum urate level reduction also remained significant in the multivariate GEE analysis (regression coefficient = −0.43 [−0.67 to −0.19] after 3 months and −0.37 [−0.64 to −0.10] after 6 months). Moreover, propensity-score-matched analyses yielded the same results.ConclusionsOur results showed that longitudinal serum urate levels were significantly reduced in men receiving ADT. This finding suggests that androgen could have an independent role in urate homeostasis.

Impact of palliative care interventions on health-related quality of life (HRQOL): A secondary analysis of the Promoting Resilience in Stress Management (PRISM) Randomized Controlled Trial (RCT).

78 Background: PRISM, a novel intervention for adolescents and young adults (AYAs), seeks to enhance resilience skills via four in-person sessions. Primary analysis of the RCT in AYAs with cancer showed PRISM improved HRQOL. This secondary analysis aimed to explore changes in HRQOL domains and differences between patient groups. Methods: English-speaking AYAs (12 - 25 years) were randomized to PRISM or usual care (UC) from Jan 2015 - Oct 2016. Surveys were completed at enrollment and six months later, using the Pediatric Quality of Life Inventory (PedsQL) Generic Short Form (SF-15) and Cancer Module to assess HRQOL. We compared change scores (PRISM vs UC) by domain (PedsQL SF-15: physical, emotional, social, school; cancer: pain, nausea, procedure anxiety, treatment anxiety, worry, cognition, perceived appearance, and communication). Participants were stratified by age (12 - 17 years vs 18 - 25 years) and advanced cancer status (yes/no). Results: 74 patients (36 PRISM, 38 UC) completed 6-month assessments. 72% were 12 - 17 years old. 23% had advanced cancer at enrollment. PRISM improved patient-reported communication (UC: median [interquartile range, IQR] 0 [-17, 8]; PRISM: 8 [0, 25]). Younger patients seemed to benefit more, especially in PedsQL SF-15 school (12 - 17: UC 0 [-8, 0], PRISM 13 [0, 17]; 18 - 25: UC 0 [-33, 17], PRISM 0 [-25, 17]) and social domains (12 - 17: UC 0 [-33, 0], PRISM 0 [0, 8]; 18 - 25: UC 0 [-25, 4], PRISM -17 [-25, 8]), and cancer-specific perceived appearance (12 - 17: UC -4 [-25, 0], PRISM 8 [-8, 25]; 18-25: UC 0 [-21, 0], PRISM -8 [-25, 17]). Patients with advanced cancer seemed to benefit in cancer-specific domains nausea (no: UC 0 [-10, 15], PRISM 10 [-10, 40]; yes: UC 6 [-15, 25], PRISM 35 [25, 50]) and pain (no: UC 13 [-13, 25], PRISM 6 [-13, 25]; yes: UC -13 [-25, 0], PRISM 6 [-13, 25]). Patients without advanced cancer seemed to benefit in perceived appearance (no: UC -6 [-33, 0], PRISM 0 [-8, 17]; yes: UC 0 [-8, 17], PRISM 4 [-8, 17]). Conclusions: With PRISM, younger AYAs were better able to cope with age appropriate challenges (social, school, appearance) and AYAs with advanced cancer improved physical symptom HRQOL. Clinical trial information: NCT02340884.

The Association of Hydration Status with Physical Signs, Symptoms and Survival in Advanced Cancer-The Use of Bioelectrical Impedance Vector Analysis (BIVA) Technology to Evaluate Fluid Volume in Palliative Care: An Observational Study.

BackgroundHydration in advanced cancer is a controversial area; however, current hydration assessments methods are poorly developed. Bioelectrical impedance vector analysis (BIVA) is an accurate hydration tool; however its application in advanced cancer has not been explored. This study used BIVA to evaluate hydration status in advanced cancer to examine the association of fluid status with symptoms, physical signs, renal biochemical measures and survival.Materials and methodsAn observational study of 90 adults with advanced cancer receiving care in a UK specialist palliative care inpatient unit was conducted. Hydration status was assessed using BIVA in addition to assessments of symptoms, physical signs, performance status, renal biochemical measures, oral fluid intake and medications. The association of clinical variables with hydration was evaluated using regression analysis. A survival analysis was conducted to examine the influence of hydration status and renal failure.ResultsThe hydration status of participants was normal in 43 (47.8%), 'more hydrated' in 37 (41.1%) and 'less hydrated' in 10 (11.1%). Lower hydration was associated with increased symptom intensity (Beta = -0.29, p = 0.04) and higher scores for physical signs associated with dehydration (Beta = 10.94, p = 0.02). Higher hydration was associated with oedema (Beta = 2.55, p<0.001). Median survival was statistically significantly shorter in 'less hydrated' patients (44 vs. 68 days; p = 0.049) and in pre-renal failure (44 vs. 100 days; p = 0.003).ConclusionsIn advanced cancer, hydration status was associated with clinical signs and symptoms. Hydration status and pre-renal failure were independent predictors of survival. Further studies can establish the utility of BIVA as a standardised hydration assessment tool and explore its potential research application, in order to inform the clinical management of fluid balance in patients with advanced cancer.

Intravitreal administration of bevacizumab in the treatment of choroidal metastasis in a patient with erlotinib-failed pulmonary adenocarcinoma

Choroidal metastasis is uncommon and usually identified in a relatively advanced cancer status. The median survival after diagnosing choroid metastasis in lung cancer patients was only 1.9months. Once failed to systemic treatment, there was no effective local treatment for saving visual acuity. The off-label use of intravitreal bevacizumab was popular in treating VEGF-mediated chorioretinal diseases worldwide. We here demonstrate a dramatic and durable response to intravitreal bevacizumab. Unlike the previous similar reports, our patient had failed both first- and second-line therapies.

Achievement of personalized pain goal in cancer patients referred to a supportive care clinic at a comprehensive cancer center.

Cancer pain initiatives recommend using the personalized pain goal to tailor pain management. This study was conducted to examine the feasibility and stability of personalized pain goal, and how it compares to the clinical pain response criteria. Records of 465 consecutive cancer patients seen in consultation at the Supportive Care Clinic were reviewed. Pain relief was assessed as clinical response (≥30% or ≥2 point pain reduction) and personalized pain goal response (pain ≤ personalized pain goal). One hundred fifty-two (34%), 95 (21%), and 163 (37%) patients presented with mild (1-4), moderate (5-6), and severe (7-10) pain, respectively. Median age (59 years), males (52%), and advanced cancer status (84%) did not differ by pain category. Median personalized pain goal at initial clinic consult was 3 (interquartile range, 2-3), was similar across pain groups, and remained unchanged (P = .57) at follow-up (median, 14 days). Clinical response was higher among patients with severe pain (60%) as compared with moderate (40%) and mild pain (33%, P < .001). Personalized pain goal response was higher among patients with mild pain (63%) as compared with moderate (44%) and severe pain (27%, P < .001). By using personalized pain goal response as the gold standard for pain relief, the sensitivity of clinical response was highest (98%) among patients with severe pain, but it had low specificity (54%). In patients with mild pain, clinical response was most specific for pain relief (98%), but had low sensitivity (52%). Personalized pain goal is a simple patient-reported outcome for pain goals. The majority of patients were capable of stating their desired level for pain relief. The median personalized pain goal was 3, and it was highly stable at follow-up assessment.

The relationship between bioelectrical impedance phase angle and subjective global assessment in advanced colorectal cancer

BackgroundBioelectrical Impedance (BIA) derived phase angle is increasingly being used as an objective indicator of nutritional status in advanced cancer. Subjective Global Assessment (SGA) is a subjective method of nutritional status. The objective of this study was to investigate the association between BIA derived phase angle and SGA in advanced colorectal cancer.MethodsWe evaluated a case series of 73 stages III and IV colorectal cancer patients. Patients were classified as either well-nourished or malnourished using the SGA. BIA was conducted on all patients and phase angle was calculated. The correlation between phase angle and SGA was studied using Spearman correlation coefficient. Receiver Operating Characteristic curves were estimated using the non-parametric method to determine the optimal cut-off levels of phase angle.ResultsWell-nourished patients had a statistically significantly higher (p = 0.005) median phase angle score (6.12) as compared to those who were malnourished (5.18). The Spearman rank correlation coefficient between phase angle and SGA was found to be 0.33 (p = 0.004), suggesting better nutritional status with higher phase angle scores.A phase angle cut-off of 5.2 was 51.7% sensitive and 79.5% specific whereas a cut-off of 6.0 was 82.8% sensitive and 54.5% specific in detecting malnutrition. Interestingly, a phase angle cut-off of 5.9 demonstrated high diagnostic accuracy in males who had failed primary treatment for advanced colorectal cancer.ConclusionOur study suggests that bioimpedance phase angle is a potential nutritional indicator in advanced colorectal cancer. Further research is needed to elucidate the optimal cut-off levels of phase angle that can be incorporated into the oncology clinic for better nutritional evaluation and management.

PATTERNS OF PAIN EXPERIENCES AND USE OF ANALGESICS AMONG HOSPITALIZED CANCER PATIENTS IN KOREA

Four hundred fifty cancer patients were selected from two public university hospitals and two private university hospitals in a large-sized city (Seoul) as well as a medium-sized city (Taegu) in Korea. Patients were interviewed regarding their experiences with pain during hospitalization and their medical records were reviewed. About 70% of cancer patients had cancer-related pain. Over 50% of the patients with pain had metastases. These findings indicate that Korean patients have relatively advanced cancer status and more severe pain compared with cancer patients hospitalized for treatment in the United States. The mean daily morphine equivalent dose, however, was 55.7 mg, which is lower than practices in the United States. Health professionals seem to rely on their preconceptions about pain and pain management. The results suggest the need for standardization of pain assessment, individualization of pain treatment, and development of educational programs for pain relief measures to improve the care of cancer patients who suffer from pain.