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Liver cancer care is evolving quicklyɾٳnew toolsand technologiesthat arehelping toexpand whattreatmentispossible for patients with both primary liver tumors andother forms ofcancer that havespread to the liver, also known as metastatic disease.
Dr. Juan Rocca,Surgical Director of the Weill Cornell Liver Cancer Program andattending surgeon specializing in liver transplantation and hepatobiliary surgery,and Dr. Manish Shah,amedicaloncologistand Director of the Gastrointestinal (GI) Oncology program at Weill Cornell Medicine,share insights into these advancesandwhy the liver is such a central organ in cancer care.
Theliveris like a giant factorythatdoes many different thingsin the body.Beyond producing bile for digestion, the liver processes nutrients and helps make proteins, hormones, and clotting factors. Italsoworks around the clock regulatingallofthe body’smetabolic functionsand isextremely important for sustaining life.
The liveris uniquely positionedin the body when it comes to the blood supply. The liverreceives blood fromboththe hepaticartery, which carries oxygenated blood from the heart,andthe portal system, which carriesnutrient-richblood from the intestinesand digestive system.
This is important for dailyprocessing andmetabolism, but if there is cancer in thedigestive system, it can deliver cancer cellsdirectlyinto the liver andspread the disease.Because ofthisportalpathway,the liveroftenbecomesa common site for metastaticcancer.
The flipside is that this very same liver anatomy and blood flow system can beleveragedto help deliver targeted cancer treatments directly into the liver.In short, the liver’tjust a site ofcancer. It can shape the entire treatment landscape.
Because many liver tumorsare largely suppliedbloodby the arterial system,delivering therapy throughthearteriescan preferentially attackliver tumors that startin the liver andcancersthat have metastasized or spread there,whilepotentiallysparingthehealthylivertissuethat isalso“fed” by the portal system.
Embolization is a type of therapythat can bedelievereddirectly to the liver tumor by the artery that supplies thattumor, andencompasses diverse treatments likechemotherapyor radiationwithY-90radioactive beads. This type of treatment cankill cancer cells in a variety of ways, including by delivering high dose radiation directly to tumors from withinorbyblockingthe cancer cellsprimaryblood supply and in some cases,cutting them off and starving the cancer cells.
Due toits role in processing nutrients and medications in the body, theliverisalso abletoinfluence treatment responses to systemic therapies– or therapies that circulate through the entire body, such as chemotherapy and immunotherapy.“Theliver can affectoverallimmunity and immunotherapyeffectiveness, andwhat’s really emerging is that if there are metastases to the liver, they can actually lead toakind of immune resistance,”Dr. Shah says.“This is shaping how we understand the immune system and why some peoplerespondbetter to certain cancer therapies than others.”
’snot clear how to overcome this type of resistance that is induced by the liver. However, combination treatment strategies are likely necessary.For example,immotherapydrugs, such ascheckpointinhibitors,can be combined with other targeted therapy drugs such as kinase inhibitors or monoclonal antibodies,or targeted therapies can be combined with chemotherapyto help overcome this resistance. These combinationsmayhelp allow the immune cells to infiltrate the tumorbetter.
When it comes totreatingprimarylivercancer andmetastaticlivertumors, surgeryremainsa cornerstoneof therapy.The liverislike a big sponge that holdsasignificant amount of blood, so traditional surgeryposessome risks.Bleeding, bile leak,and liver failureremaingeneral surgicalcomplications.
Minimally invasivesurgicalapproachesreducetheriskof complicationsfor many patients.Robotic surgerycan be thought of assurgery throughsmallkeyholes,where ahumansurgeoncommandeersa robotwith tiny armswhich actlike miniaturehands inside the body. Thistechnologycan allow complex procedures withmuchsmaller incisions and often faster recoverytimes.
For widespreadcancerin the liver,livertransplantationcan bean optionforsomepatients. Instead of cuttingout and removing selectedpieces of the livercontainingcancerous cells,the goalwithlivertransplantationis to cutoutthe entirediseasedliver, and then replace that liver with a normal, healthyliverfrom a donor. This can be donethrougheither deceased-donorsoras aliving-donor transplantbecause of theabilityof the liverto regenerate and grow back.
These advances in technologyhave enabledtreatment formorecancerpatients with diseasethatisindifficult toreachareas, as well asformetastatic cancer that has spread to the liver from other areas of the body.
For example,a newer application of liver transplant isforpatients with advancedcolorectalcancer that has metastasized to the liver.For many patients, theliver lesionscanbe removed successfully withopen,laparoscopicand roboticsurgery.However, for some patients that have too many liver metastases,the ability to offer liver transplant as a treatmentoptionforthesepatientshassignificantly improved outcomes and givenan optionto patients where other therapies are notfeasible. These patients who haveundergoneliver transplantationshave been able tolive longer without cancer progression than patients who underwent other treatments for their liver metastases.
Avariety ofapproachescan destroy tumors without removing them.Radiation therapy uses high-energy rays or particles to kill cancer cells.Radiation damages the DNA within the cancer cells, preventing the cancer from replicating and shrinking tumors.Traditional radiation therapyisgiven via amachine thatfocusesbeams of radiation on the cancerfrom outside the body, also known as external beam radiation.Stereotactic body radiation therapy (SBRT) usesprecise,focused, overlappingbeams to target livertumors while reducing radiation to nearby healthy tissue. SBRT can typically be given over a shorter course of time compared toother forms ofradiation therapy.
Ablationis another type of local therapy thattypicallyusesheatto kill cancer cellsby insertinga needle into the tumor and raising thetemperatureto“cook”thecanceroustissue.Microwaveablation is commonly usedin this manner.In this procedure, athin probe is guided directly into the tumor,andmicrowave energy rapidly heats the tissueandcausescancer cells to die.Thisallows doctors to target tumors while preserving as much healthylivertissue as possible.Another form of ablation known as cryoablation usesextreme cold instead of heat to kill cancer cells.
A newer non-invasive techniqueknown ashistotripsy uses ultrasoundwavesto target tumors. “Instead of creating hightemperaturein the area,it creates‘shock waves’,Dr. Roccaexplains. “Theythenliquefythe tissueandhelp tomelt awaytumors.Histotripsyhas the advantagethatit does not require any sort of incision or needle to go into the bodyin order totarget the cancer.”
Treatment withhistotripsyhasa potential advantage when tumors sit near critical structures likethebile ducts and blood vessels.Therationaleis thathistotripsy may not destroy the blood vessels or the bile ductsdue to thehigh collageninthem—potentially preserving the liver’s “scaffolding” whileeliminatingcancer cells.
Researchand long-termdataisstill developingas towhich patients maybestbenefit fromhistotripsy versus other localandregionalcancertreatments, but this is an excitingnew technologythat offers more options for patients.
With so manytreatmenttools available, individualized planningand a personalized approachis essential.According to Dr. Rocca,“The keytoall this is tolook at each patient, whattype of tumor they have,itslocation,andhowthe cancer hasresponded to chemotherapy or immunotherapy.’sreally importantthat we try topair the right treatment options foreachparticular case,whilelevergingthe entire toolkit that is available.”
Multidisciplinaryteam members, from across different departments including surgery, radiation oncology, interventional radiology, medicaloncologyandbeyond, allwork together to make these decisions. Factors thatthe teamevaluatesincorporatethe individual patient circumstances andtheserecommendationsdependon the number of liver lesions and theirrelative location to a blood vessel or to the bile duct, along withoverallliver function and health.
These innovationshaveexpanded the number of patients who canbenefitfrom surgery and otherformsprecisionmedicine andindividualizedcancertreatments.Often surgeonscan noweventreat cancersthat they previouslywould not haveotherwisebeen able to treat.
Dr. Shahdescribesmodern liver cancer careas“diverse and complicated, andbest delivered through teams that can combine surgery, image-guided therapies, radiation, systemic treatments, and clinical trials to match the right approach to the right patient.”
Thiscombined progress has opened doors that were not possible until more recently.Many morepatients cannowsafely undergo a variety of treatments, more challenging tumors can be targeted, and advanced disease can be treated and managedin more ways than ever before. For patients with liver cancer or cancer that has spread to the liver, the treatment landscape is expandingrapidlyas innovation continues to move the field forward.
To learn more about the evolving landscape of treatments for liver cancer and metastaticcancer that has spread from its original location to the liver, tune in to the AVоCancerCastPodcast where Drs. Rocca and Shah discuss this topic in more detail. Listen on,,, or theAVо website.
