Marilyn Fenichel

Burt Knight, 62, of Denver, received a diagnosis of stage 4 stomach cancer in 2020 that had spread to the peritoneum. He had just undergone 12 rounds of chemotherapy, but cancer cells were still present in his stomach. What’s more, his oncologist was not very optimistic, leaving Knight feeling discouraged.

Burt Knight underwent HIPEC treatment and surgery for gastric cancer, and now says he is doing well — and even went on a trip to Alaska. 

Knight was no stranger to cancer. Ten years earlier, he had received a diagnosis of colon cancer, discovered during a routine colonoscopy. 

“I was the poster child for colon cancer,” Knight recalls. “I had a colonoscopy at 50, they found malignant polyps and were able to treat the cancer surgically. I didn’t even need chemo.”

But this time, his situation was different. As Knight was pondering next steps, his family scoured the internet for treatment options. One of Knight’s daughters came across a webinar about stomach cancer with Dr. Brian Badgwell, a surgeon and oncologist at The University of Texas MD Anderson Cancer Center in Houston. He was talking about HIPEC and surgery for gastric surgery, still considered an experimental treatment in the United States.

“You could see his passion even over the computer screen,” Knight recalls. “He didn’t just want to treat cancer; he wanted to eradicate it. At that moment, I knew he was the doctor I wanted to work with.”

Knight and his wife traveled to MD Anderson and met with Badgwell. He wanted to conduct his own diagnostic tests, so he ordered an endoscopy and new scans. Although there was no sign of cancer in the peritoneum, they too, saw cancer cells in the stomach.

That concern was magnified when Knight had genetic testing and found out that he had a genetic mutation for stomach cancer that increased his chances of developing the disease to over 80%.

“Dr. Badgwell wanted me to have my stomach removed, which felt drastic,” he says. “Ultimately, however, I went that route. I had HIPEC both before and after surgery.”

Knight had his surgery two years ago and so far, so good. He stopped working and has taken several trips, including a fishing trip to Alaska. He also has a 2-year-old grandson, whom he watches every Wednesday.

“In the poker game of life, if you’re dealt a bad set of cards, the best you can do is play them as well as you can,” Knight adds. “If only 1% of gastric cancer patients beat the odds, I want to be one of those 1 percenters.”

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“In the poker game of life, if you’re dealt a bad set of cards, the best you can do is play them as well as you can,” a cancer survivor said. 

Playing the Odds in the Poker Game of Life With Cancer

Erena van der Heijden, 61, of Glendale, California, had been treated extensively for her ovarian cancer. After receiving her diagnosis in 2013, she had a total hysterectomy and received chemotherapy. When the cancer recurred in 2017, she had more surgery, where much of her colon was removed.

But neither surgery nor a wide array of drugs stopped her cancer, in large part because of the type of ovarian cancer she had. Called low-grade serous ovarian cancer, it is a rare cancer characterized by small tumors in the peritoneum, the thin layer of tissue that lines the abdominal cavity and wraps around several organs and tubes that connect them. 

"The side effects (from PIPEC) were so much less than they’ve been for either intravenous chemotherapy or the oral form."

This type of cancer is hard to treat because these small tumors are slow growing and don’t have an extensive network of blood vessels, making it difficult for chemotherapy administered through infusion to reach them. What’s more, this type of ovarian cancer is often resistant to chemotherapy. In addition, van der Heijden had developed ascites, a buildup of cancer cell-containing fluid in the abdomen.

Having tried a variety of treatments — including chemotherapy, hormone therapy and targeted therapy — with limited success, van der Heijden turned to her doctors for other options. They referred her to a trial being conducted at City of Hope, in Duarte, California, under the direction of Dr. Thanh Dellinger, principal investigator and a gyne- cologic oncologist and surgeon. Two other sites — Northwell Health in New York and Mayo Clinic in Jacksonville, Florida — are also part of the trial.

The trial is testing PIPAC, or pressurized intraperitoneal aerosolized chemotherapy, which is unique in that the chemotherapy is sprayed directly onto the tumors that lie on the surface of the abdominal cavity. This process is designed to make absorption of chemotherapy by the tumor cells more efficient and hopefully more effective. Using laparoscopic surgery, small incisions are made into the abdomen and an aerosolized form of chemotherapy is spread in the area and left there for about a half an hour. 

“We have animal data showing that the pressurized approach goes deeper into the tumor, while the aerosol helps deliver the chemotherapy more widely throughout the abdomen,” says Dellinger. “Although this procedure is given after patients have received three or four lines of treatments and is not designed to be curative, it can provide significant relief.”

That has been van der Heijden’s experience. PIPAC has given her a much-needed reprieve from both the cancer and the unsuccessful treatments she has endured. 

“The side effects were so much less than they’ve been for either intravenous chemotherapy or the oral form,” she says. “The biggest problem was fatigue, which could last anywhere from 24 hours to four days. There is also some healing from the incisions. But even with those issues, I’m a big fan of the procedure.”

“Erena has responded so well to the treatment that we gave her six treatments instead of the usual three,” Dellinger adds. “Her markers for ovarian and peritoneal cancers have dropped to levels within the normal range, and the ascites disappeared. It’s very interesting that a chemo-resistant kind of cancer is responding when the chemo is delivered a different way. We’re trying to figure out why that’s the case.”

PIPAC was first developed in Europe, and the technology has been available there for about a decade. In recent years, interest in PIPAC has grown in the United States largely because systemic chemotherapy has not been successful in treating peritoneal tumors. The search for alternative approaches resulted in this multisite clinical trial, the first testing PIPAC in the United States. 

“Unlike in Europe, the United States requires approval from the Food and Drug Administration (FDA) before a treatment can become standard of care,” says Dellinger. “This phase 1 clinical trial, which currently has about 25 patients at City of Hope, was designed to determine safety and efficacy, which we have already done.”

Dr. Richard Lawrence Whelan, chief of colorectal surgery at Northwell Health system and the Northwell Health Cancer Institute, is spearheading Northwell’s PIPAC clinical trial as an affiliate site of the PIPAC trial led by City of Hope. 

“We’ve done 18 PIPAC treatments on four patients,” Whelan says. “In two of our patients, one with colorectal cancer and the other with appendiceal cancer, the PIPAC decreased the amount of tumor such that they were now eligible for debulking, or removing the tumors on the organs, and applying HIPEC (hyperthermic intraperitoneal chemotherapy), heated chemotherapy spread onto the clean abdominal cavity. Unlike PIPAC, which is a palliative form of treatment, surgical resection and HIPEC have the potential to be curative.” 

Recent data have shown that for mesothelioma and appendiceal cancer, for which HIPEC and chemotherapy is standard of care, the five-year survival rate is now at least 50%.

Under the leadership of Dr. Mustafa Raoof, a surgical oncologist at City of Hope, the trial is being modified to include a combination of systemic chemotherapy and PIPAC for patients with colorectal and appendiceal cancer. The regimen alternates traditional chemotherapy with PIPAC. 

“Unlike the first PIPAC trial we conducted, for this one, patients don’t have to have failed a previous line of therapy,” Whelan says. “In fact, they need to have been successful on the chemotherapy before we start PIPAC. We’ve started this trial, called bidirectional treatment, with five patients. We’re also looking into starting another trial for patients with pancreatic cancer.”

At City of Hope, Dellinger is developing a bidirectional trial for patients with ovarian cancer. She’s excited about this approach and believes the two types of treatments will “synergize each other.”

As with PIPAC, physicians are looking to expand the use of HIPEC beyond the two cancers for which it is commonly done. Dr. Brian Badgwell, a surgeon and oncologist specializing in gastric and esophageal cancer at The University of Texas MD Anderson Cancer Center in Houston, was the principal investigator for the three clinical trials using HIPEC for peritoneal metastases as a result gastric cancer. He has also performed over 100 HIPEC procedures to treat these metastases. 

“Since the peritoneum is the most common site for metastases for gastric cancer, I would like to see HIPEC receive national guideline approval for this disease, especially since peritoneal disease is a horrible malignancy,” Badgwell says. “But progress is slow.”

Although PIPAC has provided tremendous relief to patients who have received it, the treatment
can have a negative side. Repeated treatments may cause scar tissue — or adhesions — to form, and vital organs may then cement together. As a result, they no longer function properly.

That’s what happened to Martin Greenwood, 63, of Lake Grove, New York. After receiving a diagnosis in 2020 of stage 4 appendiceal cancer that involved multiple areas throughout the abdomen,

he had surgery to remove half his stomach and 80% of his colon, along with some of his small intestine and his gallbladder, spleen, appendix and 14 lymph nodes. The surgery was followed by HIPEC, which, in his case, did not prove to be curative. Unfortunately, his cancer recurred a year later.

MARTIN GREENWOOD underwent PIPAC treatment for stage 4 appendiceal cancer. 

“At that point, PIPAC was my best option. There were only two slots for appendiceal cancer in the clinical trial, and I got the second one,” Greenwood says. “Although the PIPAC clinical trial only included three treatments, I was approved for an additional five by the FDA. I felt well and experienced a higher quality of life than I had in a while.”

Then things took a turn for the worse. Greenwood developed a series of bowel obstructions, a result of the adhesions, that required hospitalization. Because the organs were stuck together, he was not eligible for surgery.

Since then, Greenwood has had several more obstructions, occurring about a week apart. When they occur, he takes medication for the intense pain, stops eating and drinking, then moves onto liquids and soft foods before returning to his new low-fiber diet. 

“I’ve managed to stay out of the hospital for over a month now,“ Greenwood says. “But I can’t afford to lose any more weight. If I can’t maintain and gain weight, I will likely have to go on TPN (total parenteral nutrition), which involves having nutrition administered through a port located in a vein near my heart. The treatment is typically administered every day and takes about 10 hours, so it would be life changing.”

While Greenwood has struggled with these problems over the last couple of months, he is grateful for the symptom- and pain-free time PIPAC gave him. 

“I’ve had wonderful care at Northwell, with very compassionate nurses and doctors,” Greenwood says. “I was able to dance at my son’s wedding in 2021 and travel to Israel and Costa Rica with my wife. For that, I am forever grateful.”

Positive results have emerged from a trial testing PIPAC, a procedure used for appendiceal, ovarian, gastric and colon cancers that works by spraying chemotherapy directly onto tumors. 

An Innovative Approach to Chemotherapy

Dennis Barbee was a young man in 1979 when he started a groundskeeper business in Phoenix. Using Roundup to kill the weeds on various properties was just part of the job. For 12 years, Barbee had almost daily exposure to the common herbicide.

In 1991, Barbee moved to northern California. He was working in a different field in 2013 when he started experiencing severe gastrointestinal symptoms. After a series of tests, he received his diagnosis: mantle cell lymphoma, a type of non-Hodgkin lymphoma.

“It didn’t occur to me that Roundup had anything to do with my cancer,” Barbee recalls. “But then I saw in the news that it had been linked to non-Hodgkin lymphoma. Although none of my oncologists had suggested a link to Roundup, I suspected that it was the reason that I got cancer.”

In 2015, the International Agency for Research on Cancer (IARC), one of the agencies responsible for finding environmental toxins, also called carcinogens, identified the active ingredient in Roundup, glyphosate, as a probable cause of cancer.

Now 69 and living in Coeburn, Virginia, Barbee has paid a steep price for his long-ago exposure. After his diagnosis, he had intensive therapy, including chemotherapy, radiation and a stem cell transplant, which he tolerated well. 

He was in remission for three years but when the cancer came back in 2017, his treatment options had narrowed. He was prescribed a targeted therapy called Imbruvica (ibrutinib), which came with a host of side effects including extreme fatigue and neuropathy. 

Dennis Barbee's daily exposure to Roundup may have been the cause of his mantle cell lyphoma. 

“The fatigue was so intense that I could no longer do my job,” Barbee says. “Not only did cancer cost me my health; it also sidelined my career and left me financially insecure.”

The number of cancers linked to carcinogens is extensive. The National Toxicology Program (NTP), charged with compiling a list of carcinogens for the secretary of the U.S. Department of Health and Human Services, has identified 256 substances, including eight added in 2021. 

In selecting substances for their lists, NTP and IARC consider environmental risks, including exposure to external toxins such as air and water pollution and chemicals, as well as lifestyle issues, such as smoking, alcohol and poor diet. Therefore, it’s not surprising that the National Cancer Institute estimates that a substantial number of cancer cases can be linked to some form of exposure to these and many other substances.

Although determining the causes of various types of cancer can be challenging, some clear links have been established. 

“We know that tobacco smoke is a very powerful carcinogen, resulting in a 25-fold increased risk of lung cancer,” explains Dr. Jonathan Samet, dean of the Colorado School of Public Health in Aurora.

Dr. Edward S. Kim, physician-in-chief at City of Hope Orange County in California, concurs, adding, “Tobacco is the most notorious carcinogen of all. It doesn’t matter whether you’re a smoker or breathing in someone else’s smoke. At least 70 chemicals in tobacco are known to cause cancer.”

While active smoking can increase the risk of lung cancer by a factor of 15 to 30 (or a 1,500% to 3,000% increase in risk), second-hand smoke can increase it by a factor of 1.25 to 1.3 — or a 25% to 30% higher risk compared to a nonsmoker without smoke exposure.

The Interplay Between Carcinogens and Genes 

The reason environmental toxins are so powerful is that they have the ability to damage DNA, and damaged DNA is instrumental in the processes that lead to a cancer diagnosis. Evidence of this phenomenon has emerged through the discovery of mutational signatures, composites of mutations associated with DNA damage and repair mechanisms. 

Dr. James Herman, co-leader of the cancer epidemiology and prevention program at UPMC Hillman Cancer Center and professor of medicine at the University of Pittsburgh, points out that work is underway to identify mutational signatures in genes driving the development of cancer. 

“Scientists have identified strong mutational signatures for tobacco and UV radiation in certain genes, verifying that the cancer was caused by exposure,“ he explains.

Developments in gene sequencing have led to greater understanding of why non-smokers often get nonsmall cell lung cancer. Many of those cancers are caused by mutations in specific genes, with EGFR and KRAS among the most common.

New research presented by Charles Stanton, chief clinician at the Francis Crick Institute in the U.K. at the 2022 meeting of the European Society for Medical Oncology, showed that normal lung cells can also have these mutations, probably a result of aging. According to Stanton, this research suggests that air pollution can then initiate lung cancer in cells with these mutations. This information is another piece of the puzzle and makes a strong case for limiting air pollution worldwide.

Acting on Evidence Doesn't Happen Quickly 

Although doctors and researchers now acknowledge the link between environmental toxins and cancer, this realization took a long time to emerge. Recognition of asbestos as a carcinogen is a case in point. 

Doctors began suspecting a link between asbestos and mesothelioma, a rare cancer of the lining of many organs, including the lungs, abdomen and heart, in the 1940s, when they saw a jump in cases among people working in naval yards. By the 1960s, researchers had discovered that mesothelioma has a long latency period, taking 15 to 70 years to develop following exposure.

When Heather von St. James, 53, of Minneapolis was 7 years old, her father worked in the construction industry. He was responsible for hanging drywall, mixing the compound that was full of asbestos, and sanding walls before they were painted.

“I remember my father coming home with his jacket covered in white, grayish dust,” von St. James recalls, “but this didn’t stop me from wearing it when I did chores outside. Little did I know that the exposure to asbestos would lead to a diagnosis of mesothelioma more than 25 years later, when I was only 36.”

And the diagnosis couldn’t have come at a worse time. “I had just given birth to my baby and I had never felt sicker,” von St. James says. “I was anemic and my chest felt like a truck was sitting on it. After a CT scan and a biopsy, I received the diagnosis, but by then I already knew I had cancer.”

Heather von St. James is a patient advocate for others with mesothelioma and aims to speak out until asbestos is banned by regulatory agencies.

The prognosis was grim. Von St. James was told that without treatment, she had 15 months to live. 

“That was not an option,” she states. “Then my doctor told me about a surgeon, Dr. (David) Sugarbaker in Boston, who had pioneered surgery to treat the disease. Without blinking an eye, my husband said, ‘Get us to Boston,’ and 12 days later, we were sitting in Dr. Sugarbaker’s office. I was cleared for surgery, an eight-hour procedure where the team removed my entire left lung, the lining of the lung or pleura where the tumor was located, the left half of my diaphragm, the lining of my heart and a rib. During the surgery, they did a heated “hyperthermic” chemotherapy wash, but I still needed four additional rounds of chemo and radiation. A year later, I was declared cancer free.”

As von St. James entered the recovery phase, she began researching asbestos use in the United States and she discovered that it still hasn’t been completely banned. In 1970, the Clean Air Act authorized the Environmental Protection Agency (EPA) to regulate its use. 

As a result, in 1989, a partial ban went into effect, prohibiting the manufacture, import and distribution of asbestos, and in 2019, a regulation was added prohibiting asbestos products that had left the market to return without EPA approval. While these regulations help, it is still legal to import and use asbestos in small amounts. As a result, many products still contain more than 1% of the mineral.

Like asbestos, Roundup is still in use in the United States. What’s more, the EPA has not classified it as carcinogenic as long as users follow the directions on the label. However, with IARC designating of the chemical in Roundup as carcinogenic, many other countries have banned its use.

Regulations aside, for the legal community, enough evidence has emerged to hold the asbestos and Roundup industries accountable for the cancers their products have caused. Both von St. James and Barbee have been part of lawsuits, and both have received settlements, 3M Corp. and Monsanto/Bayer, respectively. Yet the compensation can’t erase the toll cancer has taken on their lives.

“I live with chronic pain, numbness and nerve damage, and at times, my voice is raspy and I feel short of breath. But I’m proud of the work I’ve done as a mesothelioma advocate and will continue to speak out until asbestos is finally banned,” adds von St. James.

Next Steps for Environmental Toxins Studies 

As scientists work to solidify the role of environmental toxins on cancer risk, another variable has been thrown into the mix: climate change. Concern about the impact of climate change on health spurred the American Society for Clinical Oncology (ASCO) to form a task force charged with addressing this topic.

“There’s no question that climate change has accelerated interest in the role of air pollution in cancer risk,“ says Dr. Eric H. Bernicker, a medical oncologist with Houston Methodist Cancer Center. “In fact, it is hard to decouple the discussion of air pollution from climate, largely because both are driven by the same factors, such as the burning of fossil fuels. In addition, climate change shines a light on health disparities, starkly showing that the worst air tends to be in poorer areas, and these areas also have higher rates of cancer.”

The ASCO Climate Change Task Force will begin its work by developing a policy statement about how climate change is affecting wellness and health and the strain it will put on the health care delivery system in the years ahead. 

The task force will then most likely make the suggestion that ASCO turn its attention to two broad areas of research: modeling the risks of climate change to cancer and whether a warming planet will result in an increase in certain carcinogenic viruses and cancers already linked to environmental toxins.

“We’ve already seen the effect of wildfires, floods and other major weather events on health,” Bernicker says. “For example, after Hurricane Harvey, the radiation cancer center at Houston Methodist Hospital was flooded with water, causing us to scramble to get patients treated elsewhere. We’ve fixed that problem but the experience provoked discussions on how to help patients and caregivers become more resilient.”

A big part of the push for resilience involves driving home the importance of prevention. That includes advocating for smoking cessation and less consumption of alcohol and red meat.

“We’re not trying to scare people but we do need to educate them so that they make good choices,” Bernicker adds. “They don’t need to buy a fancy treadmill to be more active; they can simply take a walk. Gaining control of what we can in our lives and avoiding exposure to toxins when possible are steps we as individuals can take. In the meantime, the scientific community will continue to do its part.”

To learn more about Heather Von St. James's story of surviving 17 years with mesothelioma, when she was originally given months to live, 

listen to this "Cancer Horizons" podcast episode

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Tobacco smoke, pesticides, herbicides and chemicals in the air are among the substances that are known to increase the risk of getting some kinds of cancer.

The Cancerous Legacy of Environmental Toxins

Heather Von. St James isn’t the typical mesothelioma cancer survivor.

In 2005, Von St. James was 36 years old and balancing caring for her newborn baby with her work as a hairstylist. She felt constantly fatigued and out of breath, but brushed it off as typical post-pregnancy symptoms.

However, after her loved ones expressed concern about her abnormal weight loss, she agreed to see the doctor, who ordered a biopsy. She was then diagnosed with malignant pleural 

, a rare cancer that occurs in the lining of the lungs.

Heather Von St. James was 36 when she received a diagnosis of mesothelioma.

Of note, according to The American Cancer Society, the average age upon mesothelioma diagnosis is 72 years old.

After the doctor explained to her that the primary cause of mesothelioma is asbestos exposure, Von St. James flashed back to her childhood. Her father was a construction worker who worked with asbestos-containing drywalls and would come home wearing a dust-covered work jacket. Von St. James often wore that jacket when she ran errands, and unknowingly breathed in toxic fumes for years.

After being told she only had 15 months to live without treatment, Von St. James traveled to Boston from Minneapolis to receive an extrapleural pneumonectomy (a procedure where the lung is removed) at Brigham and Women’s Hospital. After the procedure, she underwent four sessions of chemotherapy and 30 sessions of radiation.

Now, she has been cancer free for 17 years.

In today’s episode of the “Cancer Horizons” podcast, Von St. James explains what it’s like to navigate an “older person’s disease” as a younger woman, her journey from patient to advocate and blogger, her experiences seeking legal action against the companies that contributed to asbestos exposure in her father’s workplace, her advice to other patients with mesothelioma and more.


Learn more about Von St. James and other people who have been diagnosed with cancer after being exposed to environmental toxins, by reading this 

For more news on cancer updates, research and education, don’t forget to 

Podcasts

A 17-year survivor shares her experience of getting diagnosed with mesothelioma at 36, when people with this cancer are typically diagnosed at a much older age and given months to live. 

Marilyn Fenichel

Playing the Odds in the Poker Game of Life With Cancer

An Innovative Approach to Chemotherapy

The Cancerous Legacy of Environmental Toxins

From a 15-Month Prognosis to 17 Years of Survivorship: Heather Von St. James' Mesothelioma Story

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