Availability of palliative parenteral nutrition to patients with advanced cancer: A national survey of service provision.

BACKGROUND: Patients with advanced malignancy who are unable to meet their nutritional requirements orally or enterally as a result of intestinal failure may be considered for parenteral nutrition support. Current UK guidance recommends that patients with a 3-month prognosis and good performance status (i.e., Karnofsky performance status >50) should be considered for this intervention at home (termed Home Parenteral Nutrition; HPN). However, HPN is a nationally commissioned service by National Health Service (NHS) England and Improvement that can only be initiated at specific NHS centres and so may not be easily accessed by patients outside of these centres. This survey aimed to identify current clinical practice across UK hospitals about how palliative parenteral nutrition is initiated. METHODS: Clinical staff associated with Nutrition Support Teams at NHS Organisations within the UK were invited to complete an electronically administered survey of national clinical practice through advertisements posted on relevant professional interest groups. RESULTS: Sixty clinicians responded to the survey administered between September and November 2020. The majority of respondents responded positively that decisions made to initiate palliative parenteral nutrition were conducted in alignment with current national guidance in relation to decision-making and formulation of parenteral nutrition. Variation was observed in relation to the provision of advance care planning in relation to nutrition support prior to discharge, as well as the consideration of venting gastrostomy placement in patients with malignant bowel obstruction unsuitable for surgical intervention. CONCLUSIONS: Adherence to current national guidance in relation to the provision of palliative parenteral nutrition is variable for some aspects of care. Further work is required particularly in relation to maximising the opportunity for the provision of advance care planning prior to discharge in this patient cohort.

Population Pharmacokinetics Analysis of Pemigatinib in Patients With Advanced Malignancies.

Pemigatinib is a fibroblast growth factor receptor 1-3 inhibitor used to treat cholangiocarcinoma. A compartmental population pharmacokinetics model was developed using data from 318 patients with cancer enrolled in a phase 1 dose-escalation/dose-expansion study, a phase 1 Japanese PK bridging study, and a phase 2 cholangiocarcinoma study. The final model for pemigatinib was a 2-compartment disposition model with first-order absorption and linear elimination. All fixed- and random-effect parameters were estimated with good precision, and no apparent biases in the overall model fit were observed. For females, the estimated typical pemigatinib absorption rate constant (ka ) and oral clearance (CL/F) were estimated (1.49 L/h and 10.3 L/h, respectively). For males, the typical apparent clearance and ka are 19.0% higher and 56.5% lower, respectively, compared with females. Typical apparent volume of distribution of the central compartment (Vc /F) and peripheral compartment for a 73.3-kg patient was estimated to be 122.0 L and 80.1 L, respectively; both increased with body weight. Phosphate binder coadministration decreases typical pemigatinib CL/F by 14.1%. Proton pump inhibitor coadministration increases typical pemigatinib apparent Vc/F by 24.4%. Phosphate binders and sex contribute a <20% change to CL/F. The impact of the investigated covariates on pemigatinib pharmacokinetics are not clinically significant.

Could Camrelizumab Plus Chemotherapy Improve Clinical Outcomes in Advanced Malignancy? A Systematic Review and Network Meta-Analysis.

PURPOSE: Camrelizumab is a novel programmed cell death 1 (PD-1) inhibitor. To determine the efficacy and safety of the combination treatment of camrelizumab+chemotherapy and camrelizumab monotherapy, and determine which is the most suitable malignancy type to be treated with camrelizumab, we performed a systematic review and network meta-analysis. METHODS: We searched PubMed, Embase, and the Cochrane Library for published clinical trials from database inception until April 2021. Studies that compared camrelizumab+chemotherapy and camrelizumab monotherapy in patients with advanced malignancy were included. We estimated odds ratios (ORs) with credible intervals (CIs) using network meta-analysis with random effects. RESULTS: We included four clinical trials with 946 advanced malignancy patients. In terms of the efficacy evaluation of the objective response rate and progression-free survival, camrelizumab treatment for Hodgkin lymphoma (HL), camrelizumab treatment for esophageal squamous cell carcinoma (OSCC), and camrelizumab+chemo treatment for HL always ranked first. In terms of safety evaluation from leukocytopenia, hypothyroidism, and asthenia, camrelizumab treatment for OSCC and chemo always ranked first. This study was registered with PROSPERO, number CRD42021249193. CONCLUSIONS: Patients with advanced OSCC should be treated with camrelizumab. Patients with severely relapsed/refractory HL could use camrelizuma+chemo for combination treatment when they can tolerate adverse reactions. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=249193, PROSPERO (identifier, CRD42021249193).

Palliative Surgery for Advanced Cancer: Clinical Profile, Spectrum of Surgery and Outcomes from a Tertiary Care Cancer Centre in Low-Middle-Income Country.

OBJECTIVES: Palliative surgery for cancer plays an important role in the overall management, especially in low-middle countries with a significant burden of advanced cancers. There is a paucity of literature related to the field of palliative surgery. In this study, we present the clinical spectrum, profile of surgical interventions and outcomes of palliative surgical procedures performed at a tertiary cancer centre involving multiple organ systems. MATERIALS AND METHODS: A retrospective analysis of prospectively maintained surgical oncology database of a tertiary care cancer centre was performed. Patients fulfilling the criteria of palliative surgery were analysed for clinical spectrum, indications for surgery, palliative surgical procedures and post-operative outcomes. RESULTS: A total of 678 out of 8300 patients fulfilled the criteria for palliative surgery. Palliative surgical procedures were performed most commonly for gastro-oesophageal malignancies (36.4%) followed by colorectal cancers (24%) and breast cancer (12%). Palliative mastectomy was the most common procedure performed for advanced breast cancer and 7% of sarcoma patients had amputations. Symptom relief could be achieved in 80-90% of patients and post-operative morbidity was relatively high among hepatobiliary, gastrointestinal and gynaecological cancer patients. CONCLUSION: Globally, a significant number of cancer patients need palliative surgical intervention, especially in LMIC with a high burden of advanced cancers. Results of the current study indicate that gastrointestinal cancer patients constitute a major proportion of patients undergoing palliative surgery. Overall results of the current study indicate that excellent palliation can be achieved in majority of patients with acceptable morbidity and hospital stay.

Pharmacokinetics of carfilzomib in patients with advanced malignancies and varying degrees of hepatic impairment: an open-label, single-arm, phase 1 study.

BACKGROUND: Carfilzomib is approved in the United States and Europe for treatment of relapsed or refractory multiple myeloma (MM). This study evaluated pharmacokinetics (PK) and safety of carfilzomib in patients with relapsed or progressive advanced malignancies and varying degrees of impaired hepatic function. METHODS: Patients with normal hepatic function (normal) or hepatic impairment (mild, moderate, or severe) received carfilzomib infusion in 28-day cycles. The primary objective was to assess the influence of hepatic impairment on carfilzomib PK following 27 and 56 mg/m2 doses. RESULTS: The majority of patients enrolled in this study had solid tumors (n = 44) vs. MM (n = 2) since patients with multiple myeloma do not tend to have severe hepatic impairment in the same way as patients with solid tumors. A total of 11 normal and 17 mild, 14 moderate, and 4 severe hepatic impairment patients were enrolled. Compared with patients with normal hepatic function, patients with mild and moderate hepatic impairment had 44 and 26% higher carfilzomib AUC0-last, respectively (27 mg/m2 dose); increases at the 56 mg/m2 dose were 45 and 21%, respectively. Considerable PK variability (% coefficient of variation in AUC ≤100%) was discerned and no consistent trend of increasing exposure resulting from increasing hepatic impairment severity (moderate vs. mild) was seen. The observed adverse event (AE) profile in patients of mostly solid tumors was consistent with the known safety profile of carfilzomib, with the exception of an increased frequency of AEs consistent with hepatic function abnormalities. CONCLUSIONS: In this population of primarily advanced solid tumor patients, patients with mild and moderate hepatic impairment had approximately 20-50% higher carfilzomib AUC vs. normal hepatic function patients. These increases are unlikely to be clinically significant, in light of the intrinsic PK variability and exposure-response relationship of carfilzomib. Trial registration http://clinicaltrials.gov NCT01949545; date of registration: September 6, 2013.

Surgical palliation of gastric outlet obstruction in advanced malignancy.

Gastric outlet obstruction (GOO) is a common problem associated with advanced malignancies of the upper gastrointestinal tract. Palliative treatment of patients' symptoms who present with GOO is an important aspect of their care. Surgical palliation of malignancy is defined as a procedure performed with the intention of relieving symptoms caused by an advanced malignancy or improving quality of life. Palliative treatment for GOO includes operative (open and laparoscopic gastrojejunostomy) and non-operative (endoscopic stenting) options. The performance status and medical condition of the patient, the extent of the cancer, the patients prognosis, the availability of a curative procedure, the natural history of symptoms of the disease (primary and secondary), the durability of the procedure, and the quality of life and life expectancy of the patient should always be considered when choosing treatment for any patient with advanced malignancy. Gastrojejunostomy appears to be associated with better long term symptom relief while stenting appears to be associated with lower immediate procedure related morbidity.

Does solitary- and organ-confined metastasectomy really improve survival in advanced urologic malignancies?

The role of metastasectomy on survival in advanced/urologic malignancies still remains unclear. Renal cell carcinoma (RCC) is the most common solid tumor within the kidney. 25-30 % of patients have metastases at manifestation. Urothelial carcinoma (UC) consists of bladder carcinoma, upper urinary tract urothelial cell carcinoma and urethral carcinoma. Bladder cancer is the ninth most common cancer worldwide. Half of patients with muscle invasive bladder cancer have lymph node or distant metastases. In metastatic disease first-line treatment is multi-agent platinum-based systemic chemotherapy. Testicular cancer is the most common cancer in men between the age of 15 and 35. Testicular tumors represent excellent oncologic outcomes. Prostate cancer is the most common solid tumor in Europe. Surgical resection of metastases can be considered as a treatment choice in advanced/metastatic urologic malignancies to improve survival rates, particularly in RCC and UC. Metastasectomy can be suggested in conjunction with effective chemotherapy if complete resection is possible. Solitary metastasectomy can represent better survival rates compared to multiple metastasectomy even if multiple metastases confined to single organ. Site of metastases is one of the main determinants of successful metastasectomy such as lung metastasectomy in urothelial cell carcinoma and liver metastasectomy in RCC may lead to better oncologic outcomes. Due to the lack of the relevant data it is not possible to make an evidence-based recommendation on the role of metastasectomy for solitary-/organ-confined metastases of prostate cancer, testicular cancer and penile cancer.

A multidisciplinary approach in providing transitional care for patients with advanced cancer.

Patients living with a diagnosis of an advanced life-limiting malignancy often have concerns regarding symptom burden, physical and psychosocial impact on life, and questions surrounding end-of-life processes. Due to the complex care needs of patients with advanced life-limiting illness it is our experience that both a multidisciplinary and interdisciplinary approach to care can optimize the patient and family illness experience for this vulnerable population. Progressive metastatic illness often necessitates care in multiple settings including an ambulatory clinic, inpatient hospital ward, at home, and at an in-patient hospice or palliative care unit. Palliative care teams are typically composed of clinicians from various disciplines who work in multiple settings and can act as a link between community, ambulatory and in-patient care-settings. The team often includes physicians, advance practice nurses [nurse practitioners and clinical nurse specialists (CNSs)], nurses, social workers, chaplains, and other allied health clinicians. The result of this team approach, in collaboration with oncology providers, makes palliative care an ideal model for providing care through the many transitions that are inherent to patients living with advanced malignancy.

Incidence of depression in patients with advanced malignancy and its effect on quality of life / 肿瘤研究与临床

Objective To investigate the incidence of depression in patients with advanced malignancy and its effect on quality of life.Methods Patients with advanced malignancy were evaluated with Beck depression and quality of life questionnaires.The correlation of Beck depression scoring with quality of life was analyzed.Results A total of 230 in-patients with advanced malignancy were enrolled in this study and 213 copies of valid questionnaire were collected.95.3 ％ (203/213) patients had depression.The Beck depression scoring had positive correlation with body,role,mood,cognition,society,vomiting,pain,dyspnea,agrypnia and appetite (all P ＜ 0.05),and had negative correlation with total health factors (r =-0.296,P ＜ 0.01).Conclusion Depression is prevalent in patients with advanced malignancy and correlated with quality of life.Therefore,psychological interventions are needed to relief depression and improve quality of life.