Sorafenib in Liver Function Impaired Advanced Hepatocellular Carcinoma

Objective To explore the efficacy and safty of sorafenib in Child-Pugh class B to class C hepatocellular carcinoma （HCC）. Methods In this three-center open-label study from November 2011 to May 2013, we randomly assigned 189 patients with advanced Child-Pugh class B or C HCC patients into two groups, one group with 95 patient to receive sorafenib （400 mga time, twice a day） and the other group with 94 patients to receive best supportive care. The primary end points were progression-free survival and overall survival. Results The median progression-free survival was 2.2 months and 1.9 months in the sorafenib group and best supportive care group respectively （Hazard ratio in the sorafenib group, 0.55; 95% confidence interval, 0.40-0.75; P=O.O02）. The median overall survival was 4.0 months and 3.5 months in the sorafenib group and best supportive care group respectively （Hazard ratio in the sorafenib group, 0.48; 95% confidence interval, 0.35-0.68; P〈0.001）. The main adverse effect of sorafenib was rash and ache of the skin （in 51.7% patients）. The incidences of severe rash, diarrhea, and dry skin were 5.6%, 5.6%, and 2.2% in the sorafenib group. One patient reached partial response in the sorafenib group. Conclusions Sorafenib is safe in patients with liver function impaired advanced HCC. It is effective in terms of progression-free survival and overall survival compared with best supportive care. Liver functions are the important predictive factors.

Difficult Conversations and Painful Decisions: When Should Patients with Progressive Cancer Stop Chemotherapy?

Introduction: The decision to stop anti-cancer treatment is fraught with many challenges for the oncologist, the patient, and their caregivers. This review examines the special considerations surrounding the decision to cease chemotherapy in terminally ill cancer patient. Methods: A comprehensive literature search was conducted to find relevant publications on chemotherapy cessation. A total of 2700 records were retrieved and 141 were identified as eligible for inclusion in this review. Results: Palliative chemotherapy does not achieve the goal of tumor-related symptom reduction for patients who have experienced progressive disease with more than two prior lines of chemotherapy. ECOG performance status is a crucial predictor of response to therapy and chemotherapy-related complications. Challenges to stopping chemotherapy at the end of life are multifactorial and are both patient and physician-driven. Racial, ethnic, and income-based disparities are seen in the timing and quality of end-of-life conversations offered by physicians to their patients. Conclusions: The decision to cease chemotherapy is one that should be approached with careful consideration and accurate information. Clear communication, compassion and empathy are important components to the therapeutic relationship. Early involvement of palliative care and clear conversations about prognosis and the expected utility of further chemotherapy is essential to conduct the best possible care for cancer patients at the end of life.

Pre-transplantation cytoreduction does not benefit advancedmyelodysplastic syndrome patients after myeloablative transplantation with grafts from family donors

Background:The role of pre-hematopoietic stem cell transplantation(HSCT)cytoreduction with either induction chemotherapy(IC)or hypomethylating agents(HMAs)in treating advanced myelodysplastic syndrome(MDS)remains debatable.We aimed to evaluate pre-HSCT strategies by comparing the endpoints related to disease control between advanced MDS patients with pre-HSCT cytoreduction and those with best supportive care.Methods:We described 228 consecutive advanced MDS patients who received HSCT from a haploidentical donor(HID,n=162)or matched related donor(MSD,n=66)with uniform myeloablative conditioning regimens between January 2015 and December 2018.Of these 228 patients,131(57.5%)were treated exclusively with pre-HSCT best supportive care(BSC),49(22.5%)were given HMA,and 48(21.1%)received both IC and HMA.Propensity score-matching analysis,multivariate analyses,and subgroup analyses were performed to elucidate the impact of pre-HSCT strategies on transplant outcomes.Results:The 3-year relapse-free survival(RFS)rates were 78.2% and 70.0% for the BSC and cytoreduction cohorts(P=0.189)and were 78.2%,66.7%,and 73.2% for the BSC,HMA,and HMA+IC groups,respectively(P=0.269).A propensity score-matching analysis confirmed that the 3-year RFS rates were 81.9%,87.5%,and 66.9% for BSC,cytoreduction complete remission(CR),and cytoreduction non-CRgroups,respectively(P=0.051).Multivariate analyses demonstrated that pre-HSCT cytoreduction,older patient age,monosomal karyotype,and interval between diagnosis and HSCT were poor prognostic factors for RFS.In the subgroup analyses,BSC was associated with longer RFS compared to cytoreduction among the younger patients,those with international prognostic scoring system intermediate-2/high risk at diagnosis,and those with intermediate/poor cytogenetics.Conclusions:Different pre-HSCT therapies did not yield discrepant post-HSCT outcomes.No benefit in terms of post-HSCT outcomes were correlated with pre-HSCT cytoreduction in advanced MDS even for cytoreduction CR patients.Early referral to HSCT is essential for advanced MDS patients.