This is a vivid account of a surgical procedure performed at City of Hope. The details may be disturbing for some readers.
Striding through the swinging doors that lead into the operating theater, his arms upright and dripping water after scrubbing in, Behnam Badie, M.D., carries himself with the sure air of a neurosurgeon.
The procedure he is about to perform, involving meticulously excavating a tumor from a patientâs brain, is one he has done thousands of times. But there is one difference.
If the patient, a 44-year-old male, has active tumor growth, he will be eligible for a clinical trial involving using his own immune system cells to fight his brain cancer.
âThis patient has had a glioblastoma, which is a pretty aggressive tumor,â says Badie, chief of the Division of Neurosurgery at City of Hope, as a nurse wraps him in a gown before surgery. âOur plan is to explore the previous surgical area, expose the brain and get biopsies. If thereâs evidence that thereâs recurrence, the plan is to remove the tumor.â
For this and other patients being considered for the clinical trial, qualifying is a complicated reality. No new tumor growth is good news, but likely temporary. Glioblastomas almost always come back â quickly and with a vengeance.
On the other hand, even a shred of evidence of tumor growth for this patient would mean qualifying for the trial â and being treated with an advanced therapy that could extend his life.
The surgery is a rescue mission in two phases. The first, removing a tumor that is impairing the patientâs physical functioning, and causing his moods, according to his wife, to swing wildly from listless to aggressive to confused. The second phase involves preparing the patient for a new type of therapy called chimeric antigen receptor, or CAR T cell therapy to target his brain tumor.
âWe all know the three main pillars for cancer therapy: surgery, chemotherapy and radiation,â says Christine Brown, Ph.D., associate director of the T Cell Therapeutics Research Laboratory at City of Hope and co-lead with Badie on the trial. âAnd weâve improved in all those areas, but I think the most exciting is this new fourth pillar of immunotherapy where weâre trying to empower a patientâs immune system to both recognize and destroy their cancer.
âWeâre utilizing the power and potency of specialized white blood cells called T cells and reprogramming them. What this does is allow T cells to see cancer cells that they couldnât see before. And when they see them, they seek out those cells and kill them.â
How CAR T cell therapy works, as explained by Saul Priceman, Ph.D.
What is unique about the therapy is that CAR T cells â immune system cells, removed from the patient, genetically altered, then reintroduced to the patient to bolster his bodyâs ability to fight his cancer â will be infused directly to the brain using delivery tubes called catheters.
One catheter will be pointed at the cavity where the patientâs tumor was growing, to target any leftover cancer cells. The other will be directed into the cerebrospinal fluid, a clear liquid that bathes the brain and spinal cord, to do the same.
âThis direct-to-brain approach is unique to City of Hope,â says Brown, The Heritage Provider Network Professor in Immunotherapy. âWe were the first to implement this approach. Very few centers in the world can do this.â
This rescue mission has tremendous implications. The patient has three young children and a wife whose lives will be challenged if he is not enrolled in the clinical trial. A familyâs future hangs in the balance of this surgeryâs outcome.
Two nurses and neurosurgeon Lisa Feldman, M.D., Ph.D., position the patient on the table so his head is angled properly for surgery. A nearby whiteboard, in shorthand, explains the procedure: âRight craniotomy for tumor resection. Placement of Rickham reservoir and catheter.â
A screen above the operating table displays the silver contours of the patientâs face alongside digital images of the interior of his brain. Feldman points a long metal navigation probe, which looks a little like an old-fashioned TV antenna, toward a section of the patientâs skull. With each touch of the probe, a 3D image of a section of the brain is revealed on a nearby screen.
It is used by the surgeons throughout the procedure to guide them â indicating where they are in the brain, and which structures could be affected by their surgical instruments.
âIt allows us to see how far we are in certain brain regions,â says Badie. âTo see whether we are almost at the expected edge of where the tumor is growing.â
âIncision,â says Feldman as her voice rings through the OR. She begins to cut through the patientâs scalp. Underneath is a bone flap â a section of the skull bone that will be removed, revealing the portal through which the surgeons will access his brain.
Badie joins Feldman and the two neurosurgeons hover over the patient, working together to remove tiny flecks of bone that surround the flap; putting them, one by one, into a plastic cup. Soon, they will use a screwdriver-type device to dislodge the bone.
An hour earlier, the patient â whose history includes three years of treatment, including brain surgeries, radiation, chemotherapy and experimental therapies â told his wife he wanted to give up. There had been too many surgeries. Too many procedures. Too much time trying to save his life at the expense of living out his remaining days.
âI told him, 'You have two options,'â recalls his wife. âYou go home, wait for the tumor to keep growing and you die. Or you go through another surgery and say to yourself, at least I tried it all.â
The bone flap removed, Badie points the navigation probe toward the brain. He begins cutting and peeling away the dura, a thick, protective layer of tissue that covers the brain and spinal cord. Soon, the patientâs brain is exposed: a spongy mass of grayish-pink fatty tissue.
Badie extracts a piece of tissue for biopsy: âRight frontal glioma versus gliosis,â he says, indicating the type of tissue to be assessed by pathology, either tumor tissue or scar tissue.
âNavigation probe,â says Badie, gesturing again for the instrument that helps visualize the brain.
âItâs registered,â answers Feldman.
Badie then maneuvers a large microscope so it is positioned above the opening in the patientâs brain.
The surgeons take turns navigating brain areas that a recent MRI indicated could be harboring new tumor growth, pulling out fatty white tissue as they go.
âLooks like he had a hemorrhage,â says Feldman, as she holds up the next sliver of tissue, which has more of a brownish tinge.
Inside the OR there is a rhythm unfolding: the sound of suction to remove tiny rivulets of blood bubbling up from the brain, alternating with the beep of a cauterizing device. The patientâs brain appears to be pulsating in response to the surgeonsâ work.
Feldman cranes her neck at intervals to get a better look at the navigation screen. She asks for a receptacle for a specimen, remarking that it ââ¦looks like scar tissue.â
Badie begins calling out the type of specimen, âThis is â¦â before a nurse finishes his sentence, ââ¦ right frontal glioma versus gliosis.â
After handing over the specimen, Badie turns to Feldman and says, âWe need to save a lot of that tissue.â
Enough tissue to get an accurate gauge of whether there is active tumor growth.
âThatâs scar,â says Feldman, holding up brain tissue. âSee it? Iâll stay away from that.â
She continues pulling at tiny popcorn-like parcels of tissue inside the patientâs brain. A red light shines into a region that, magnified by the microscope, looks like a cavernous tunnel in the brain. Feldman uses a scraping motion as she digs, as if she is carving out a mini ditch around the tissue she is targeting.
âGet a little bit of the sides,â says Badie. âMake sure you remove the tissue.â
âCan I have the scope?â says Feldman.
Feldman continues to pull out white slivers of scar tissue. She uses long tweezers to transfer each fatty looking piece to a tray, preparing to send them to pathology.
The challenge is that the scar tissue is in the resection cavity â the space where the patientâs tumor has grown in the past. If it turns out the greyish hues they saw on the MRI are not new growth, but old scar tissue, the patient will not be eligible for the trial.
âWhat we could be seeing is radiation necrosis,â says Feldman. âItâs actually one of the biggest problems in neurosurgery. Glioblastoma is a nasty tumor, so we often donât know if what weâre seeing is radiation injury from all the treatment the patient has undergone, or itâs tumor coming back.â
Inside brain surgery. WARNING: Some scenes in this video are graphic.
âThis part feels really firm,â says Feldman, as she continues probing the brain. Meanwhile, Badie is on the phone with pathology, getting the analysis of tissue previously sent.
âThe pathologist called back,â says Badie. âHe sees abnormal cells but heâs not sure if itâs new tumor growth or the previous tumor. So we are going to send some new samples to see if we have some viable tumor cells.â
Badie places a small mesh sheet into the tumor cavity to help stanch bleeding. He alternates between this and cauterizing, or burning, tissue to keep small blood vessels in the area from bleeding.
âIf we donât have hemostasis, the patient could develop a blood clot in the surgical cavity,â explains Badie.
Feldman is on the phone with pathology, getting final confirmation about the patientâs eligibility for the trial.
âOkay, focally recurrent GBM with the background of necrosis,â says Feldman to the pathologist before turning to Badie and saying, âWe got our diagnosis.â
âThatâs a bittersweet diagnosis,â she continues. âBoth good because now heâs going to be eligible to get into the clinical trial, but obviously itâs bad to have a recurrent tumor. But with this tumor itâs expected.â
A nurse places thin tubes and two small dome-shaped reservoirs on a tray so Badie and Feldman can assemble and later implant them.
Badie examines sections of tumor tissue he is excising and hands them to a nurse who drops them into tubes nearly filled with colored liquid.
The image being transmitted by the overhead microscope reveals the path traveled by a probe being used to position one of the catheters. As it penetrates the brain tissue, bright reddish and gray hues splash across the screen. The inside of the patientâs brain, during this part of the procedure, looks like a piece of abstract art.
Feldman uses the scope to help position a catheter so that it points toward the tumor cavity.
âCan I have the reservoir?â asks Feldman, gesturing for the device that will help deliver the CAR T cells while she again irrigates the wound opening.
âIâm getting the second catheter ready,â says Badie, as he assembles the tubing and reservoir that will be placed near the cavity in the middle of the brain that houses much of the patientâs cerebrospinal fluid.
As Badie places the second catheter, Feldman begins drilling tiny screws into the bone flap to prepare it to again cover the patientâs brain.
An air of finality has settled into the operating room. The anesthesiologist checks the patientâs stats. A nurse walks in with a kit that will be used to repair the patientâs dura. Nearby, nurses work together to count sponges and equipment.
The neurosurgeons stand at either side of the surgical wound and alternate between stitching the dura closed using thin, thread-like sutures.
The rescue mission was successful. The patient qualified for the trial.
âFor us it is a mixed feeling,â says Badie. âYou donât want there to be tumor and youâre hopeful itâs just scar. So, itâs sad this patient has recurrent disease. But at least we can try and improve his quality of life and longevity with CAR T cell therapy.â