John McCain discontinues cancer treatment

Sen. John McCain's family released a statement saying the senator is discontinuing treatment for his aggressive form of brain cancer.

Posted: Aug 25, 2018 7:54 PM
Updated: Aug 25, 2018 8:15 PM

Glioblastoma, an aggressive type of cancer that can occur in the brain or spinal cord, quickly became a household term after Sen. John McCain was diagnosed with the brain tumor in July 2017.

McCain died Saturday evening at age 81.

How exactly is glioblastoma treated?

Average survival for malignant glioblastoma tends to be about 14 months with treatment -- and it is difficult to treat, according to CNN Chief Medical Correspondent Dr. Sanjay Gupta, a practicing neurosurgeon.

"The general approach is to offer patients a combination of radiation and chemotherapy as a first-line treatment," said Dr. Matthias Holdhoff, a medical oncologist and associate professor of oncology in the brain cancer program at Johns Hopkins University School of Medicine in Baltimore.

"Based on this, we're trying to build on that standard of care," he said.

So, in the future, there might be more cutting-edge treatment options for glioblastoma patients.

"There are many exciting areas in research in primary brain cancers, and most clinical trials are in gliobostomas, in part because they are the most common primary brain cancers in adults," Holdhoff said.

A 'quest for finding better treatments'

Clinical trials being conducted across the United States are exploring immunotherapies, vaccines and targeted therapies in addition to traditional treatments, said Dr. Manmeet Ahluwalia, a brain tumor oncologist, professor and director of the brain metastasis program at the Cleveland Clinic in Ohio.

His team at the Cleveland Clinic has enrolled patients in a number of clinical trials for glioblastoma treatments.

According to the National Institutes of Health's clinical trials database, 274 glioblastoma multiforme studies across the country are active or recruiting.

"The brain tumor community is very united in our quest for finding better treatments for our patients, and I think the progress will come through clearly planned and orchestrated clinical trials, looking at both approaches, immunotherapies ... and appropriate uses of targeted therapies, which will go and attack the genes that drive a particular tumor," Ahluwalia said.

As for potential vaccine options, "the hope is that we are using vaccines to keep the tumor from coming back," he said.

These treatment options, which are still in early phases of research, are not yet approved and available for the general public. As the research is still ongoing, it remains unclear how much any of the potential treatments would someday cost.

Targeted cancer therapies

Targeted cancer therapies are drugs or other substances that block the spread of the disease by targeting and interfering with specific molecules involved in its growth and progression, according to the National Cancer Institute.

Though such therapies may sound promising in theory, study results have been unexpectedly disappointing, said Dr. Eric Holland, senior vice president and director of the human biology division at the Fred Hutchinson Cancer Researcher Center in Seattle.

"Individual drugs and combinations of them that hit more than one target have all been tried, and thus far, they've not really shown a whole lot of promise or certainly have not been as successful as we have liked," Holland said.

Some side effects of targeted cancer therapies include diarrhea; liver problems, such as hepatitis and elevated liver enzymes; skin problems; problems with blood clotting; and high blood pressure, according to the National Cancer Institute.

Immunotherapy

On the other hand, some studies have shown immunotherapies to work well against certain cancers, such as melanoma and lung cancer, he said. Yet more research is needed to determine the promise of immunotherapies for glioblastoma.

Cancer immunotherapy is a type of treatment that harnesses the body's own immune system to recognize, target and attack the disease, similar to how the immune system helps the body fight infections and other diseases.

Some side effects of immunotherapies include skin reactions, flu-like symptoms, heart palpitations, sinus congestion, diarrhea or even fatal allergic reactions, according to the National Cancer Institute.

Immunotherapies can come in many forms -- vaccines, antibody or cellular therapies, or drugs -- and can be received through an injection, a pill or capsule, a topical ointment or cream, or a catheter.

"There is a great deal of excitement about some of the immunotherapy-based approaches in treatment of glioblastoma," Ahluwalia said. "Immunotherapy has been shown to be promising in a number of other cancers, like lung cancer and melanoma. We are currently evaluating a number of such approaches. The ones which are most furthest along are some trials that are evaluating nivolumab, which is an anti-PD1 therapy in combination with chemotherapy and radiation."

In other words, the immunotherapy drug nivolumab unleashes an immune system attack on cancer by blocking the activation of a protein called PD-1, which would otherwise inhibit that attack, according to to MD Anderson Cancer Center. The hope is to extend the life of the patients with this treatment.

The diseases in which immunotherapies have shown promise, from skin to lung cancers, tend to involve tumor types that have many point mutations in them, Holland said. Point mutations are changes in specific locations in the tumor's DNA.

For instance, "in melanoma, it's the sun's damage to DNA, and smoking causes the lung damage" in lung cancer, Holland said.

When such genetic mutations occur in a tumor, they can cause the tumor to appear like a pathogen or foreign substance in the body, which the immune system can recognize and attack when triggered by an immunotherapy.

However, "brain tumors tend not to be that way," Holland said. "They tend to not be caused really by point mutations. They don't have a lot of point mutations in them."

Of all things, a modified poliovirus was found to infect and attack glioblastoma in an experiment at Duke University.

In May 2012, the virus was injected directly into the tumor of a glioblastoma patient as an investigational therapy. In the months following, the tumor started to shrink, without the use of chemotherapy or radiation.

Research focusing on poliovirus immunotherapy and glioblastoma remains ongoing.

While "it's certainly a very interesting concept ... this concept would also need to be rigorously tested further," said Holdhoff, who was not involved in the study. "We need to see how data will pan out when it's studied in a study that's looking at actual efficacy and overall benefit."

Cancer vaccines

Cancer vaccines, in particular, are another treatment approach in the immune space.

Such vaccines are classified as active immunotherapies because they rely on activation of a patient's immune system to recognize and destroy a tumor, according to a 2014 paper in the Journal of Immunology Research.

As a treatment, cancer vaccines are intended to treat an existing cancer by strengthening the body's natural immune response against the cancer, according to the National Cancer Institute.

"Vaccines will target a very specific antigen, and it could be, for example, a mutation that's found in the tumors, and that would make that tumor cell recognized by the immune system, and you could vaccinate against it," Holland said, adding, "It's not completely clear how well those work."

Tumor treating fields

A novel treatment approach for recurrent glioblastoma also includes tumor treating fields, a sci-fi-like therapy involving alternating electric currents, used in combination with chemotherapy.

The noninvasive treatment, which transmits cancer-fighting electric fields through the patient's skin around a region of the body containing a tumor, can be used to treat other types of cancer as well.

It works by sending low-intensity electric fields through the scalp, or other areas, that interfere with cell division in an effort to stop the cancer from spreading.

For glioblastoma, patients wear a device that delivers the treatment on their shaved scalps. Adhesive bandages can hold such devices in place.

In 2015, researchers attending the American Society of Clinical Oncology's annual meeting presented data demonstrating that a tumor treating fields device could extend glioblastoma survival by more than two months when added to chemotherapy, though it was costly. At the meeting, treatment with a tumor treating fields device was estimated at $20,000 per month.

A more recent study published in the journal JAMA found that adding tumor treating fields to the standard chemotherapy treatment of glioblastoma patients -- compared with chemotherapy alone -- could result in longer survival.

The study involved 695 cancer patients who had completed initial radiochemotherapy but still showed evidence of progressive disease. Patients were enrolled in the study from 2009 to 2014 and then followed up through 2016.

After a 40-month followup with the patients, the researchers found the addition of tumor treating fields, compared with chemotherapy alone, resulted in longer survival from the time of the study, 6.7 months versus 4 months, and longer overall survival, 20.9 months versus 16 months.

Yet the study had some limitations, including a possible placebo effect: Patients knew whether they were receiving the additional tumor treating fields treatment, due to continuously carrying the device.

"These findings are in contrast to the more than 23 randomized trials conducted over the last decade that have evaluated novel agents or intensified treatment strategies (eg, dose-dense temozolomide, cilengitide, nimotuzumab, bevacizumab, and rindopepimut) for treatment of patients with newly diagnosed glioblastoma and have failed to demonstrate improved survival. Innovative treatments for glioblastoma are needed," the researchers wrote in the study.

Many of these cutting-edge treatments, however, come with challenges.

Challenges and enthusiasm

No matter the treatment option, Holland said, crossing the blood-brain barrier remains to be a challenge for any brain cancer treatment approach.

The barrier includes a network of blood vessels and tissue that not only helps keep harmful substances from reaching the brain, it might block medicines from entering the brain.

"It's certainly one of the biggest challenges," Holland said. "Of all the drugs that are out there, really it's a small percentage of them that can get into the brain in any reasonable concentration that would be effective."

Nonetheless, Holdhoff, the oncologist at Johns Hopkins Medicine, said that the significant interest in glioblastoma treatment research shows no signs of slowing down.

"There is a great need for more research, and there is great enthusiasm across the board to improving on our standard of care," he said.

Mississippi Coronavirus Cases

Data is updated nightly.

Cases: 500286

Reported Deaths: 9968
CountyCasesDeaths
Harrison34281537
DeSoto32039402
Hinds31911626
Jackson24466379
Rankin21971390
Lee15501235
Madison14566279
Jones13825242
Forrest13438250
Lauderdale11984316
Lowndes11003188
Lamar10510135
Pearl River9494237
Lafayette8542139
Hancock7727126
Washington7418157
Oktibbeha7139131
Monroe6765176
Warren6679176
Pontotoc6655102
Neshoba6625206
Panola6511131
Marshall6460134
Bolivar6302148
Union601294
Pike5815152
Alcorn5662101
Lincoln5431134
George496579
Scott472198
Tippah468381
Prentiss466581
Leflore4654144
Itawamba4628105
Adams4584119
Tate4579109
Copiah447792
Simpson4440116
Yazoo443687
Wayne439172
Covington428694
Sunflower4235105
Marion4225107
Coahoma4154104
Leake408088
Newton381679
Grenada3703108
Stone359764
Tishomingo359492
Attala331089
Jasper329565
Winston314091
Clay307676
Chickasaw299467
Clarke292194
Calhoun278945
Holmes267887
Smith263350
Yalobusha233347
Tallahatchie226851
Walthall218763
Greene218248
Lawrence212440
Perry205256
Amite204755
Webster202646
Noxubee186440
Montgomery179456
Jefferson Davis171442
Carroll168738
Tunica159439
Benton148438
Kemper141941
Choctaw133326
Claiborne132237
Humphreys129238
Franklin119428
Quitman106428
Wilkinson104839
Jefferson94434
Sharkey64020
Issaquena1937
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Alabama Coronavirus Cases

Cases: 815989

Reported Deaths: 15311
CountyCasesDeaths
Jefferson1144621915
Mobile723961330
Madison52114694
Shelby37488348
Baldwin37167547
Tuscaloosa35013606
Montgomery34031734
Lee23177245
Calhoun22190476
Morgan20719376
Etowah19774497
Marshall18277302
Houston17333411
St. Clair15967339
Cullman15365292
Limestone15270198
Elmore15126284
Lauderdale14205294
Talladega13783276
DeKalb12598260
Walker11142369
Blount10132175
Autauga9910146
Jackson9819182
Coffee9190191
Dale8874185
Colbert8803201
Tallapoosa7063198
Escambia6755130
Covington6695184
Chilton6608161
Russell626659
Franklin5947105
Chambers5563142
Marion4966126
Dallas4902200
Clarke474083
Pike4722105
Geneva4567126
Winston4493103
Lawrence4286117
Bibb423686
Barbour356576
Marengo337489
Monroe330863
Randolph328263
Butler325396
Pickens314182
Henry311865
Hale310688
Cherokee301660
Fayette291379
Washington251151
Cleburne247160
Crenshaw244075
Clay241268
Macon231763
Lamar219547
Conecuh185753
Coosa179439
Lowndes174464
Wilcox167839
Bullock151644
Perry138440
Sumter132038
Greene126244
Choctaw87827
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