HJNO Jul/Aug 2023

56 JUL / AUG 2023 I  HEALTHCARE JOURNAL OF NEW ORLEANS ONCOLOGY waiting time of six months or longer. Options for bridging therapy include embolization, RFA, EBRT, or partial hepatectomy. Ineligible for transplant, no macrovas- cular invasion, limited intrahepatic tumor burden: There is no single best approach to these patients, and clinical practice is vari- able. We suggest locoregional liver-directed therapy (i.e., ablation, arterially-directed ther- apies, external beam RT) rather than initial systemic therapy. Liver-directed therapies have high local response rates (up to 70%), favorable rates of local tumor control (66 to 90%), and favorable safety profiles. • Local thermal ablation (RFA, MWA) is a preferred approach for those with one or a few relatively small tumors. The best results are in patients with one or two tumors <3 cm in diameter. • Other liver-directed treatments (i.e., TACE and bland embolization, transar- terial radioembolization [TARE], HAIC, and EBRT, including SBRT) are generally reserved for tumors confined to the liver but not amenable to local ablation. He- patic arterial embolization is an option for patients with a large unresectable or multifocal HCC who have relatively preserved liver function (i.e., Child-Pugh class A or B cirrhosis) and no extrahe- patic tumor spread, vascular invasion, or tumor thrombus involving the main portal vein. Large intrahepatic tumor burden: For patients with liver-isolated HCC who are not candidates for surgical resection or liver transplantation and who have a sizeable in- trahepatic tumor burden, we suggest initial systemic chemotherapy rather than locore- gional treatment alone or combined systemic and locoregional treatment. Locoregional plus systemic therapy: Lo- coregional therapies are increasingly being tested in combination with systemic thera- pies for HCC, including molecularly-targeted agents and immunotherapy. Randomized tri- als have not demonstrated benefit from the addition of systemic therapy to TACE or any other formof arterial embolization compared with arterially directed therapy alone, and this is not a standard approach, at least for patients with a limited intrahepatic tumor burden. Extrahepatic disease or otherwise ineli- gible for locoregional therapy: For patients who are ineligible for resection, transplan- tation, or liver-directed therapy because of underlying liver disease or the presence of extrahepatic spread, or for patients demon- strating progression on locoregional therapy, systemic therapy is an option if performance status and underlying liver function are ad- equate. The field of systemic therapy for HCC is evolving rapidly, and modern therapies, including molecularly targeted agents and immunotherapy, have produced significant gains in overall survival relative to support- ive care alone. • If a clinical trial is not available or trial participation is not feasible, for healthy patients with an Eastern Cooperative Oncology Group performance status of 0 or 1, no worse than Child-Pugh class A cirrhosis, are not receiving thera- peutic anticoagulation, and following management of esophageal varices, we suggest atezolizumab plus bevacizum- ab rather than sorafenib or lenvatinib monotherapy. For patients who cannot receive bevacizumab, tremelimumab plus durvalumab is an alternative to bevacizumab plus atezolizumab. • If monotherapy with a molecularly tar- geted agent is chosen for initial ther- apy, we prefer lenvatinib rather than sorafenib for most patients because of the better tolerability (especially for hand-foot skin reaction, alopecia, fa- tigue, and anorexia) and the higher ob- jective response rates (ORRs) and longer time to tumor progression (TTP) in the REFLECT trial. Second-line therapy: For patients who are not eligible for clinical trials or if they are not available, options for patients initially treated with atezolizumab plus bevacizumab or dur- valumab/tremelimumab include sorafenib, lenvatinib, regorafenib, cabozantinib, or, where available, apatinib. n Sukesh Manthri, MD, is a medical oncologist and the medical director at Terrebonne General | Mary Bird Perkins Cancer Center in Houma, Louisiana. He re- ceived a medical degree from the Prathima Institute of Medical Sciences in India. He completed a clinical research fellowship in Cleveland Clinic Florida followed by an internal medicine residency at Southern Illinois University in Springfield.Subsequently,he completed a hospice and palliative medicine fellowship at Saint Louis University, St. Louis, Missouri. Manthri, was a medical oncology fellow at East Tennessee State Uni- versity,Johnson City. In 2020,Manthri received the Dr. Thomas G.RonaldAward for Excellence in the Care of the Cancer Patient. He is board certified in oncology, internal medicine, hospice, and palliative medicine. “HCC is the world’s fourth leading cause of cancer-related deaths and the most rapidly growing cause of cancer deaths in the U.S.”