Confused About Immunotherapy and Its Side Effects? You Aren’t Alone

“You don’t look like you have cancer.”

More than one patient undergoing immunotherapy to treat cancer has reported hearing statements like that. Immunotherapy is one of the recent advances in cancer treatment that belie the stereotypes about the effects of cancer treatment. 

The side effects of immunotherapy are different from those associated with chemotherapy and radiation. However, that does not mean immunotherapy does not have side effects. Patients and care partners need to be aware of these potential side effects and to be vigilant in addressing them with their oncologists because they can signal more serious complications if left untreated.

What is Immunotherapy?

Despite the increase of immunotherapy treatment options in recent years and considerable media attention paid to advancements in this field, there remains confusion about immunotherapy and its side effects. Many cancer patients are unaware of whether immunotherapy treatments are available for their specific diagnosis. Others don’t know that genetic profiling of their tumors is usually required to determine if immunotherapy is an option and not all treatment centers routinely conduct genetic profiles of tumors. A  survey by The Cancer Support Community found that the majority of patients who received immunotherapy knew little to nothing about it prior to treatment and were unfamiliar with what to expect.

Immunotherapy works by manipulating the patient’s immune system to attack cancer cells. It is perceived as gentler and more natural than chemotherapy and radiation, without the same destructive effect on the body’s healthy tissues.  This, combined with a lack of prior understanding of immunotherapy, can lead patients and care partners ill-prepared for possible side effects.

Furthermore, immunotherapy is a category of therapies, not a single type of treatment. There are a variety of immunotherapy drugs, most of which are administered via infusion.  Side effects will vary by drug, the cancer and its location, treatment dose, and the patient’s overall health.

The following are the most common types of immunotherapy.

  • Checkpoint inhibitors use drugs to block proteins in the patient’s immune system that would otherwise restrain the immune system, often referred to as taking the “brakes” off the immune system.
  • CAR-T therapy modifies the patient’s T-cells in a lab to enhance their ability to bind to cancer cells and attack and kill them.
  • Oncolytic virus therapy uses genetically modified viruses to kill cancer cells.
  • Another therapy uses cytokines (small proteins that carry messages between cells) to stimulate the immune cells to attack cancer.

Immunotherapy can be part of combination therapy. It might be combined with chemotherapy. It might be used to shrink a tumor that is then surgically removed.  Or multiple immunotherapy drugs might be used simultaneously.

What Are The Side Effects?

With immunotherapies, side effects typically occur when the immune system gets too revved up from the treatment. The most common side effects for immunotherapy treatments are fatigue, headache, and fever with flu-like symptoms. Some people also experience general inflammation often in the form of a rash. Many melanoma patients report blotchy skin discoloration, called vitiligo, during treatment. These milder side effects can usually be managed with over-the-counter remedies and adjustments to daily activities.

For checkpoint inhibitors, the fastest growing segment of immunotherapy treatments, mild side effects occur in 30% – 50% of patients. Serious side effects typically occur in less than 5% of patients. (See “Understanding Immunotherapy Side Effects” from the National Comprehensive Cancer Network and the American Society of Clinical Oncology.)

Less common side effects are blisters, joint pain, thyroid inflammation, and colitis (inflamed colon resulting in diarrhea with cramping). Some patients who receive CAR T-cell therapy develop a condition known as cytokine release syndrome, which causes fever, elevated heart rate, low blood pressure, and rash. 

In rare cases, immunotherapy has resulted in lung inflammation, hepatitis, inflammation of the pituitary, and detrimental effects on the nervous and endocrine systems. In most cases, the conditions clear up when treatment ends.  However, there have been outcomes in which immunotherapy caused diabetes or tuberculosis.

“Overall there are fewer side effects [with immunotherapy],” explained Dr. Justin Gainor, a lung and esophageal cancer specialist at Mass General during an Immunotherapy Patient Summit hosted by the Cancer Research Institute. “But the immune system can affect anything from the top of the head down to the toes. Any organ has the potential to be affected.”

As the application of immunotherapy has expanded, so has our understanding of the potential side effects. Like most medical treatments, how one person responds to immunotherapy can be different from another even when the cancer diagnosis and drug therapy are the same.

The essential thing patients and care partners need to know about side effects is they should always be reported to their oncologist or nurse oncologist.

Why Patients Should Talk to Their Provider About Immunotherapy Side Effects

Because immunotherapy has created newer therapy options, there isn’t the volume of experiences as with older treatments. The infinite number of variables that patients provide once a treatment moves beyond clinical trials and into the general patient population generate more diverse outcomes.  And, as most therapies are less than 10 years old, there hasn’t been an opportunity to study the long-term effect of these therapies. This is why oncologists advise patients and their caregivers to be extra vigilant in noting any changes experienced during and after treatment.

Many side effects are easy to treat but medical providers want patients to be forthcoming in discussing any and all side effects. This is in part to improve understanding of side effects, but also because a mild cough or a case of diarrhea might be harbingers of a more systemic issue that will grow worse if left untreated.

Patients should not be hesitant to discuss side effects because they fear they will be taken off immunotherapy.  Sometimes a pause in treatment might be necessary, but the earlier the oncologist is made aware of a side effect, the less likely that will be necessary.

In addition, patients undergoing immunotherapy should always take the name(s) of their immunotherapy drugs and the name of their oncologist when seeing medical professionals outside of their cancer treatment team. This is especially important when visiting the ER.  Because immunotherapy drugs are newer and highly targeted to certain cancers, many medical professionals remain unfamiliar with drug interactions and treating related side effects.

Immunotherapy On The Rise

Immunotherapy treatments have resulted in reports of remission in cases that would’ve been deemed hopeless just five or 10 years ago.  The Federal Drug Administration (FDA) has approved various immunotherapy treatments for melanoma, lung cancer, head and neck cancer, bladder cancer, cervical cancer, liver cancer, stomach cancer, lymphoma, breast cancer, and most recently bladder cancer.  (Here is a list of  immunotherapies by cancer type from the Cancer Research Institute.)

“It’s revolutionized how we treat our patients,” says Dr. Gainor of Mass General about immunotherapy’s impact on lung and esophageal cancer.

Advances in immunotherapy research and trials continue to generate optimism and excitement. A clinical study in Houston is looking at using immunotherapy to prevent a recurrence. Researchers in Britain recently announced a discovery that might lead to advances in immunotherapy treatments to a much broader array of cancers.

While there is excitement around the field of immunotherapy and it has resulted in unprecedented success in treating some previously hard-to-treat cancers, it remains an option for a minority of cancer diagnoses.  It works best on solid tumors with more mutations, often referred to as having a high-mutational load or microsatellite instability (MSI) high. And it is not universally successful for every patient.

With hundreds of clinical trials involving immunotherapy alone or in combination with other therapies, it is certain more treatment options are on the horizon. As more therapies are developed and more patients with a greater variety of conditions undergo immunotherapy, we will also increase our understanding of potential side effects.

Side effects should not dissuade patients and care partners from considering immunotherapy if it is available or from advocating for genetic tests to deteimine if it is an option. Many patients undergoing immunotherapy have previously undergone chemotherapy and report that the side effects are fewer and milder by comparison.  The important thing is that patients and their partners know what to expect and communicate with their treatment team.

If the next 10 years in immunotherapy research and development are anything link eth elast 10, we can expect more exciting advancements in the battle against cancer. For more perspective on what’s ahead for immunotherapy see the Cancer Research Institute’s article: Cancer Immunotherapy in 2020 and Beyond.

Ovarian Cancer, Sex and Intimacy podcast

This podcast was originally posted on December 11, 2018 by Target Ovarian Cancer here.

“A diagnosis of ovarian cancer and the resulting treatment can cause emotional and physical difficulties which can impact on your sexuality, sex life and relationships. We caught up with Lynn Buckley (Clinical Nurse Specialist and Psychosexual Therapist) to answer your questions and talk about what physical and emotional issues you may face and how you can seek help and support.”

Mayo Clinic Radio: Ovarian Cancer Treatment Options

On the Mayo Clinic Radio podcasts, Dr. Amanika Kumar, a Mayo Clinic gynecologic surgeon, explains how thorough assessment of a patient can help direct the treatment for ovarian cancer. This interview originally aired Aug. 24, 2019.

Ovarian Cancer Treatment

This was originally published on Lab Tests Online here.

When abnormalities are found and ovarian cancer is suspected, a surgical biopsy is required to confirm the diagnosis. If cancer is found, surgery to remove the cancerous tissue is performed (oophorectomy). Depending on the stage of the disease, additional tissues may have to be removed. One of four stages of cancer is identified depending on the spread of the tumor. They are:

  • Stage 1 – cancer is confined to one or both ovaries (about 20% of ovarian cancers diagnosed with best prognostic outcomes)
  • Stage 2 – cancer has spread to the uterus and/or fallopian tubes
  • Stage 3 – cancer has spread to the abdomen lining or surrounding lymph nodes (most common stage seen at time of diagnosis)
  • Stage 4 – cancer has spread to other organs beyond the abdomen

Follow-up treatment usually involves chemotherapy, hormone therapy, targeted therapy, sometimes radiation treatments, and monitoring of CA-125AFP, or hCG for response to treatment and recurrence.

Ovarian cancer treatment is constantly evolving. New drugs, immunotherapies, gene therapies, and bone marrow transplants are being studied for their effectiveness. A woman’s healthcare provider and/or cancer team can help determine the treatment course that is right for her.

Gynecologic Cancer Screening Guidelines

This resource was originally published by Loyola University Medical Center here.

Screening Guidelines for the Early Detection of Gynecologic Cancers

Screening tests are used to look for disease before you exhibit any symptoms, and are effective when they detect disease early, leading to more effective treatment and positive outcomes. 

American Cancer Society recommends the following screening guidelines for early detection and prevention of gynecologic cancers:

  • Cervical cancer –  Regular testing for cervical cancer should begin at age 21 for cervical cancer prevention. If you are between the ages of 21 and 29, you should have a screening test every three years. Between the ages of 30 and 65, you should have a screening test every five years. If you are over the age of 65 with normal cervical cancer test results, you should no longer be tested. Women over the age of 65 with a history of cervical pre-cancer should continue to be tested for at least 20 years.
  • Uterine cancer – The American Cancer Society recommends that at the time of menopause, all women should be told about the risks and symptoms of endometrial cancer, which may include abnormal vaginal bleeding or discharge, or pelvic pain and pressure. Some women, due to their history, may need to consider having a yearly endometrial biopsy.
  • Ovarian cancer – There are not currently any screening tests available for ovarian cancer. Doctors often perform a pelvic exam, which includes checking the ovaries, but this exam does not generally detect ovarian cysts unless they are very large. Doctors rely on the common symptoms of bloating, abdominal pain and change in urinary symptoms to guide them in the detection of ovarian cancer. If you believe you are at risk for ovarian cancer, Loyola offers a cancer risk assessment program, which provides detailed risk assessments for patients with a susceptibility to ovarian cancer.
  • Vaginal and vulvar cancer – Currently, there are no screening tests available for vaginal and vulvar cancer. The best way for you to know if you might have these cancer types is to get regular check-ups and notify your doctor if you have any signs or symptoms. Your doctor may perform a pelvic exam to look for lumps or changes in your vagina or changes in the skin of your vulva.

Each specific type of gynecologic cancer has its own unique set of risk factors, and there is no way to know who will get gynecologic cancer. Doctors at Loyola are committed to working with you to understand your specific family and medical history and symptoms to develop a screening program specific to your needs. 

What Screening Tests are Available for Gynecologic Cancer?

Cervical cancer is the only gynecologic cancer for which there is a specific screening test, the Pap smear. The Pap test helps prevent cervical cancer by finding precancerous cells that might eventually become cervical cancer. If these cells are detected, doctors at Loyola are able to remove cells and prevent cancer development.

In addition to the Pap test, an HPV test can be performed to look for the HPV virus, a common sexually transmitted virus that, if left untreated, may cause gynecologic cancers. If you are between the ages of 30 and 65, your doctor should perform an HPV test in conjunction with your Pap test. 

Young women can receive an HPV vaccine that will protect against the types of HPV that most commonly cause cervical, vaginal and vulvar cancers. The vaccine is given in a series of three shots, and is recommended for girls ages 11 and 12.

Other gynecologic cancers rely on you to understand your body and work with your doctor if you develop any unusual symptoms or changes in order to detect any cancers early.

If you are concerned about the possibility of gynecologic cancer due to family history, symptoms or screening results, contact your primary care physician who can make additional recommendations for your specific concerns.

Exploring a New Delivery Model for Germline Genetic Testing for Patients With Ovarian Cancer

This was originally published by The Journal of Clinical Oncology on March 20, 2018 here.

This podcast provides comment on the accompanying JCO article “ENGAGE: Evaluation of a streamlined oncologist-led BRCA mutation testing and counseling model for patients with ovarian cancer” by Nicoletta Colombo, et al and evaluates the need for new delivery models for genetic testing for oncology patients.

Related Article: Evaluation of a Streamlined Oncologist-Led BRCA Mutation Testing and Counseling Model for Patients With Ovarian Cancer

Ovarian Cancer Testing

This resource was originally published by Lab Tests Online here.


Currently, there is no specific screening test for ovarian cancer. In 2012, the U.S. Preventive Services Task Force (USPSTF) reaffirmed a 2008 recommendation against screening women for ovarian cancer. This recommendation applies to asymptomatic women but not to women at a high risk of developing ovarian cancer, such as those with a genetic mutation (e.g., BRCA mutation).

The need for a reliable method for early detection of ovarian cancer among asymptomatic women continues to drive ongoing research. Molecular (gene) tests and multimarker approaches are being explored to improve early detection of ovarian cancers. For example, the OVA-1 blood test, which measures levels of five proteins, is used to categorize tumors in ovarian cancer patients as low or high risk. In the meantime, regular physicals, pelvic exams, and an awareness of family history and symptoms are important.

Laboratory Tests

  • CA-125 (Cancer antigen 125) – this is the main laboratory test used to detect and monitor this condition in symptomatic women, even though this tumor marker is not recommended for screening.
  • HE4 (Human epididymis protein 4) – a relatively new tumor marker that shows promise is; it is used to monitor epithelial ovarian cancer in treated patients.
  • BRCA-1 and BRCA-2 – genetic tests that can determine if a woman is at high risk of developing ovarian cancer, but these tests are not used for diagnosis or monitoring.

Other tests that may be ordered to help detect and monitor different types of ovarian tumors include:

Non-laboratory Tests

Non-laboratory tests that are used to evaluate abnormalities include:

  • Ultrasound (pelvic and/or transvaginal) – uses sound waves to create a picture of the uterus and ovaries; it can help determine whether an ovarian growth is likely to be a cancer or a fluid-filled cyst.
  • CT scan (computerized tomography)
  • X-ray of the gastrointestinal tract
  • MRI (magnetic resonance imaging)

It is important to have regular checkups and to consult with a healthcare practitioner if symptoms develop. Symptoms associated with ovarian cancer are subtle and non-specific, and there are many non-cancerous conditions that can cause similar symptoms.

Related Video


How am I Diagnosed with Ovarian Cancer?

This article was originally published by the National Ovarian Cancer Coalition here.

Most women with ovarian cancer are diagnosed with advanced-stage disease (Stage III or IV). This is because the symptoms of ovarian cancer, particularly in the early stages, often are not acute or intense, and present vaguely. In most cases, ovarian cancer is not detected during routine pelvic exams, unless the doctor notes that the ovary is enlarged. The sooner ovarian cancer is found and treated, the better a woman’s chance for survival. It is important to know that early stage symptoms can be difficult to detect, though are not always silent. As a result, it is important that women listen to their bodies and watch for early symptoms that may present.

Did You Know?

The Pap test does not detect ovarian cancer. It determines cervical cancer.

Screening Tests

Although there is no consistently-reliable screening test to detect ovarian cancer, the following tests are available and should be offered to women, especially those women at high risk for the disease:

  • Pelvic Exam: Women age 18 and older should have a mandatory annual vaginal exam. Women age 35 and older should receive an annual rectovaginal exam (physician inserts fingers in the rectum and vagina simultaneously to feel for abnormal swelling and to detect tenderness).
  • Transvaginal Sonography: This ultrasound, performed with a small instrument placed in the vagina, is appropriate, especially for women at high risk for ovarian cancer, or for those with an abnormal pelvic exam.
  • CA-125 Test: This blood test determines if the level of CA-125, a protein produced by ovarian cancer cells, has increased in the blood of a woman at high risk for ovarian cancer, or a woman with an abnormal pelvic examination.

While CA-125 is an important test, it is not always a key marker for the disease. Some non-cancerous diseases of the ovaries can also increase CA-125 levels, and some ovarian cancers may not produce enough CA-125 levels to cause a positive test. For these reasons the CA-125 test is not routinely used as a screening test for those at average risk for ovarian cancer.

Positive Tests

If any of these tests are positive, a woman should consult with a gynecologic oncologist, who may conduct a CT scan and evaluate the test results. However, the only way to more accurately confirm an ovarian cancer diagnosis is with a biopsy, a procedure in which the doctor takes a sample of the tumor and examines it under a microscope.

Research into new ovarian cancer screening tests is ongoing and new diagnostic tests may be on the horizon. NOCC monitors the latest scientific developments. Please visit our Research page for additional information.

Ovarian Cancer: What You Need to Know with Dr. Chad Michener

This podcast was originally published by the Cleveland Clinic on April 23, 2010 here.

Ovarian Cancer: What You Need to Know with Dr. Chad Michener

How common is ovarian cancer and how do symptoms typically present? What are the risk factors? How is ovarian cancer diagnosed and treated? Join Chad Michener, MD as he answers these questions and many more.

Podcast Transcript:

Scott Steele:  Butts & Guts, a Cleveland Clinic podcast, exploring your digestive and surgical health from end to end.

Hi and welcome to another episode of Butts & Guts. I’m your host, Scott Steele, the chairman of colorectal surgery here at the Cleveland Clinic in beautiful Cleveland, Ohio. And we’re very glad today to have Dr. Chad Michener, who is the interim chair for the department of sub specialties in women’s healthcare. Chad, welcome to Butts & Guts.

Chad Michener:  Thanks, Scott.

Scott Steele:  So we always like to start out this with a little bit of background about our guests. And so tell us a little bit about where you’re from. Where’d you train and how did it come to the point that you’re here at the Cleveland Clinic?

Chad Michener:  Long story, actually, so I actually grew up in Springfield, Ohio, one of four kids. I had three sisters. Regular high school, thought I was actually going to go to art school, and kind of out of the blue decided that wasn’t going to be a great stable choice for me. So I went to college with no real plans and kind of just fell into medical school. And then on through went into training for obstetrics-gynecology, and then really enjoyed the surgical aspect. So did a cancer training fellowship at Cleveland Clinic, actually, and then stayed on board for the last 15 years.

Scott Steele:  Fantastic. Well, we’re lucky to have you here. So today we’re going to talk a little bit about ovarian cancers. So give us the 50,000-foot view of ovarian cancer. What is it, and how does it affect the daily lives? What are some symptoms?

Chad Michener:  So ovarian cancer is one of the unfortunate diseases that we find late. So it’s about 23,000 cases a year. We see, unfortunately, about 14,000 women die because we don’t often find it early. And it’s really because of the symptoms don’t always show up until pretty late. So the symptoms are pretty vague. So it kind of fools patients. It fool’s physicians sometimes because it’ll show up as bloating, nausea, I can’t really eat, I have heartburn, relatively new symptoms for patients. And so oftentimes, they’ll go down the pathway of, “Oh, you have an ulcer,” or things of that nature. And so there’s a little bit of a delay in diagnosis there, but generally speaking, we’ll still find that in stage three or stage four about 75% of the time.

Scott Steele:  So we use a lot of these terms, stages this and that. Before we get to the actual staging of it, talk to me a little bit about risk factors. There’s a lot of risk factors with every cancer. Are there risk factors associated with ovarian?

Chad Michener:  So most of the risk factors are things that are not typically preventable. So there’s no big family component; although, about 25% are going to be genetic when you really do all the genetic analysis on patients. However, there are some things that can be protective. So people who have been on birth control pills, it can reduce their risk by 40 to 50% after using those for five years. Having children is protective, breastfeeding is protective. Essentially, anything that limits the number of menstrual cycles a woman has in her lifetime, is things that can decrease that as much as possible. Things you don’t really have control over are what age they start having menstrual cycles or how many years they have menstrual cycles. So the little things in between become important.

Scott Steele:  So when you have these type of symptoms, is it spread all over the place, or how do you differentiate between what is “normal” and what is something that’s concerning? Is there any one of those symptoms that are real red flags that you would say to the women to get in and see their doctors?

Chad Michener:  So not any one symptoms. So they actually looked at studies of healthy women going in for breast screening versus women with pelvic masses that were benign and then, of course, a group of ovarian cancer patients, and the symptoms were actually fairly similar. The big difference was is that patients with ovarian cancer, the symptoms were relatively new to them and they happen more days than not over the course of three or four weeks. So if you’ve got new symptoms that aren’t going away, they’ve been lasting for three or four weeks, they’re there most days, it’s probably worth a discussion; although, a lot of times it’s not going to be ovarian cancer. It’ll be sort of the more common other things.

Scott Steele:  Okay, so I’m a woman. I’m experiencing these symptoms. I’m going to come into your office for an appointment. What can they expect during that appointment and how is this diagnosed?

Chad Michener:  So most times they’re going to do a pelvic exam and a regular exam on the abdomen. If they don’t find much there, or let’s say they feel maybe there is some fullness or thickening in the pelvis, then usually that’ll be followed with an ultrasound. And then depending on what the ultrasound shows, they may get more imaging to follow. We don’t often use markers to look for this because most times the marker can be nonspecific, so it can be elevated for other things, essentially.

Scott Steele:  And by a marker, you mean blood tests?

Chad Michener:  Blood tests, yeah. So in this case, most times we’re talking about a blood test called a CA 125. We don’t use it for screening because it can be elevated for other reasons. But in somebody who has, say, an ovarian cyst or a pelvic mass, that may be a test that follows up to the ultrasound results.

Scott Steele:  And so you have to have a tissue diagnosis in many of these cancers. Is there something that you do to get a tissue diagnosis to confirm that it’s ovarian cancer?

Chad Michener:  So we do, if it looks like there’s a lot of spread already and we’re not quite sure that that’s what it is. Sometimes we’ll do a biopsy that the radiologist will do, using a CT scan or an ultrasound to guide their biopsy. But oftentimes, we’ll actually take patients to the operating room to make the diagnosis ourselves, particularly if it just looks like an ovarian cyst, maybe with some other questionable features. And most times that’ll be done with a laparoscopy, so a little incision through the belly button with a camera. And then they can put in a couple extra working channels to take out cyst, take out the ovary, and then get a diagnosis that way.

Scott Steele:  So before we go into the actual treatment, and let’s just say that they’re facing this operation that you’re talking about, is there anything that women can do to prepare themselves for that operation?

Chad Michener:  Nothing particular. It’s obviously a little scary for them. So trying to just sort of do normal routine stuff is helpful. There will be sort of things that will follow the day before surgery. We’ll have them be on a liquid diet rather than on a kind of heavy diet so that it can kind of clean stuff out through the intestines and make surgery potentially a little bit easier. But other than that, nothing really per se that we get patients ready for.

Scott Steele:  So in other cancers, you have radiation therapy, oncology, you have surgery, you have chemotherapy up front, chemotherapy afterwards. What’s the initial therapy for ovarian cancer? And as you lead into that, can we go back to that concept you talked about, about staging? What are the different stages of it?

Chad Michener:  So stages of ovarian cancer. As a general rule, you’re going to have stage one, which is just confined to the ovary and there’s a little sub stages of that. Stage two would be that it’s outside of the ovary but still confined to the pelvis itself, so it hasn’t spread into the abdominal cavity at all. Stage three would be abdominal involvement, and that can be really anything. It tends to spread on the surfaces of the organs. And so you’ll see little implants, and they can cover the intestines, the liver, a fatty apron called the omentum that hangs off to the intestines is a very common site that we see. And then anything that’s either inside of one of those organs, let’s say there’s a cyst in the liver that’s involved or if it’s in the chest, then it would be a stage four.

Treatment is based on those stages. So if we think it’s confined to stage one, or at least it appears to in surgery, then we do a staging operation where we would take out the ovary, usually the uterus and the other ovary as well. And then we would do lymph node biopsies. We would biopsy the omentum and then biopsy different sites in the abdominal cavity where we often see spread and then followed by chemotherapy in most but not all cases. Advanced stage disease, we spend a lot of time up front getting imaging, sometimes getting biopsies before going to the operating room, to figure out what the diagnosis is and how much involvement there is, to decide if we think we’re going to be able to remove all of the tumor surgically.

If we think that that’s going to be not possible or unlikely, then oftentimes, we’ll start chemotherapy as our first treatment after a biopsy diagnosis and then plan surgery after a few rounds of chemotherapy. So that’s called neoadjuvant chemotherapy. In surgery, we’ll do what we call a debulking operation. We’ll go in, we’ll take out everything possible that we can, and sometimes that can be done laparoscopically. Sometimes it has to be done as a large open incision. And then, if we’re able to shrink everything down surgically, we actually can offer hyperthermic intraperitoneal chemotherapy, or often called HIPEC, and that actually has been associated with better outcomes in people who have neoadjuvant chemo therapy first.

Scott Steele:  That’s kind of honed down in some specifics there. So what can women expect with chemotherapy? And when you talk about a few cycles, how long is that? What side effects do they get from that? Is their hair going to fall out, or is it something that they can tolerate well? If they’re having that bloating, does that get better?

Chad Michener:  Yeah. So chemotherapy for ovarian cancer generally comes in three-week cycles, so 21 days. And sometimes that’ll be weekly treatments, sometimes be just once every three week treatments. It’s actually a fairly tolerable regimen, but there are common side effects such as hair loss. Some people will experience some nausea, but not a lot of vomiting with that regimen. They can get constipation or diarrhea. It’s pretty variable, but those can be side effects of our anti-nausea drugs. And then sometimes people were experienced neuropathy, so they get numbness or tingling in their hands or their feet. And that can be reversible over time, but we do watch that carefully because one of the drugs is associated with neuropathy more than others. After three cycles of that, so nine weeks, we would get another set of cat scans and then decide if it’s something that we can take to the OR at that point.

Scott Steele:  So when you go to the operating room and you’re trying to get out this tumor or multiple tumors in there, is it something that you have to take out other organs? Do people wake up? Do they have to wear a bag? What does that surgery all involve?

Chad Michener:  Yeah, generally speaking it’s going to be hysterectomy, and then the tubes and the ovaries, the omentum commonly. And then the other organs that can be involved oftentimes can be the appendix, the spleen, the intestines, whether that be small intestine or large intestine. And probably about 20% to 30% of patients will have some sort of a intestinal surgery during their debulking operation, most commonly the colon that sits behind the uterus. But most times, we’re able to take that out, put the colon back together, and there’s no ostomies or bags that patients would have to wear. Probably less than 5% of the time, we’ll end up doing a colostomy or an ostomy that is a temporary in most cases. Once in awhile it will be permanent, but that’s a very, very small percentage of patients.

Scott Steele:  So one of the things we know is that there’s different biologies associated with not only just classes of tumors, but within each class of tumor, individual variations exist. So there was a study that recently came out regarding a more of GI cancers about the HIPEC that you talked about, that heated intraperitoneal chemotherapy, that showed that HIPEC wasn’t as advantageous as just getting the tumor out alone. If I heard you right, that HIPEC’s a little bit different beast in terms of the ovarian cancer. What is the role of HIPEC, and who would be a candidate for HIPEC versus just the debulking surgery?

Chad Michener:  So HIPEC for ovary cancer, in fact, is actually relatively new. It’s not done in a lot of centers. And so we’re still trying to figure out exactly who the best patients are for this. As a general rule, we haven’t used it based on cell type. So if it’s an epithelial ovarian cancer, whether it’s serous or mucinous or clear cell or endometrioid, all of those patients are potential candidates, assuming that they’re having a good response to chemotherapy and they have a near complete or near complete debulking surgery. We don’t often use it for what we call germ cell tumors or stromal tumors, which we typically will see in younger women, kind of different population. We don’t know that, say, mucinous tumors are better, which is commonly what it was used for for GI tumors. But I think we just don’t have the data yet. So we kind of offer it to everybody who we’re doing a debulking operation on who’s had chemo up front because there is a survival advantage there, at least in the one study.

Scott Steele:  So how long can women expect to be in the hospital after this? Is it a pretty safe surgery to recover from?

Chad Michener:  Yeah, people do pretty well. So all complications, including wound infections or anything of that nature, bladder infections, you’ll see that in somewhere between 15% and 20% of patients, usually minor complications. Major complications like blood transfusions and things, readmissions to the hospital, retake backs to the operating room, usually we’ll only see that in about 5% of patients depending on the center. Most times, they’re in the hospital for anywhere from about three to 10 days. And it really depends on how much is done in surgery. If there’s bowel surgery or not bowel surgery, if they have a large transfusion for bleeding, they have to go to the ICU, they’ll end up staying longer in the hospital. But I think, as a general rule, people will be usually home within three to 10 days.

Scott Steele:  And do they have to get follow up chemotherapy?

Chad Michener:  Yeah, so if they started with chemotherapy, then usually we’ll finish with three more cycles of chemotherapy, so an additional nine weeks. And we generally try to start that three or four weeks after surgery. If they didn’t get chemotherapy up front and we just took them for a debulking surgery, or if they had early stage disease, then usually they’ll get all of their chemotherapy after, which usually consists of six cycles of chemotherapy.

Scott Steele:  One of the things that you had mentioned was a little bit about the younger women population was a little bit different group, but can you talk a little bit about … I’m sure this does affect some younger women. Is there a role for kind of preserving fertility or egg freezing or anything like that? And also, is there a role for genetic testing?

Chad Michener:  So fertility in younger women, we do try to preserve, in fact. And if it is, let’s say, a germ cell tumor, so a different form of ovary cancer, usually affects women in their teens, twenties, not so common after the thirties. Oftentimes, you can take one ovary out, do the biopsies for lymph nodes and things, and leave the other ovary. Oftentimes, do chemotherapy and then they’ll still maintain their fertility afterwards. There are some other things you can do. We’ll usually have them see one of our infertility experts and talk about either protective drugs for the ovaries during chemotherapy or we do offer them the potential to go through a cycle of intro vitro fertilization, freeze eggs, freeze embryos if we think they have time for that. Or sometimes I’ll actually harvest and freeze part of the ovarian tissue as well. So that would be that group.

It’s harder to do in people with advanced disease, obviously, because they’ve got disease covering a lot of areas. So typically, we won’t recommend fertility preservation in that specific sense. But sometimes we’ve taken out ovaries, left uterus behind if the uterus doesn’t look involved, and then there’s ways to do donor eggs and things like that for fertility in the future if they do well. The second question was genetic testing. And for that we actually offer genetic testing to all of our women with epithelial ovarian cancer, so the more classic ovarian cancer that we talk about, because about 20% to 25% of people will have some gene mutation in their family.

And that becomes important for two reasons. One is that that can be passed on about half of the time, so with each pregnancy there’s a 50% chance of passing that gene on. And then secondly is we actually utilize that as part of our treatment now with a group of drugs called PARP inhibitors, and those are oral medications that are taken either with or most times following chemotherapy, and they have a specific function in patients with BRCA mutations or similar mutations. And so it becomes an important part of the treatment paradigm for those patients as well.

Scott Steele:  What if you have a woman out there that says, “Listen, I don’t get this because I get a yearly pap smear.”

Chad Michener:  Yeah, that’s a common misconception. I think that people think they’re getting checked for this all the time when they go for their pap smear, and pap smears are really meant to look for cervical cancer and that’s it. It is true, once in a while we’ll find either a fallopian tube or and ovarian cancer or even sometimes an endometrial cancer, but it’s not designed for that. In fact, most people who have endometrial or ovarian cancer have a normal pap smear at the same time that they get diagnosed. So it’s not really for that.

Also on pelvic exams, sometimes people don’t have large masses. So they can have lots of disease scattered all over the abdominal cavity, and the ovaries can actually feel quite normal. And that’s because we lump ovarian cancer in with something called fallopian tube cancer, but also with one called primary peritoneal cancer where the majority of the disease is in the lining surface of the abdominal cavity, but really doesn’t involve the ovaries much at all. And so you can have normal exam and then three months later show up with bloating, nausea, and then be diagnosed with ovarian cancer.

Scott Steele:  So what’s on the horizon for the treatment or diagnosis of ovarian cancer?

Chad Michener:  So the Holy grail would be screening, right? So we don’t find it early. So if we could find a great screening test where we could find patients in early stage, it’d be wonderful because survival rates for stage one cancers are actually pretty great. The problem with finding it late is that survival rates aren’t as good. And so the research is been looking for a new marker for a long time. As I said, CA 125, not really that specific, so you can’t use that to screen kind of a normal population of women because there’s a lot of what we call false positives. So people get a positive test, they don’t actually have ovarian cancer, they have anything else. Inflammation of anything in the abdominal cavity or in the chest can cause that number to go up. So that’s one of the big things that lots of people are pushing for.

On the treatment side, I think everything is going, as with most cancer, to targeted therapies, things other than chemotherapy. And so hyperthermic chemotherapy, it was one of them, and I think that’s still a work in progress. We’re still trying to figure out how to fit that in. And then with targeted therapy, most of our trials now contain not only chemotherapy but either PARP inhibitors, other targeted inhibitors, and actually sometimes immunotherapy or a combination of those. So that’s where all the research is going currently.

Scott Steele:  Well, that’s fantastic stuff, and we’re glad to have you here. This one hits particularly close to home as my mother passed from it. So, Chad, we are going to just kind of wind up with a few quick hitters for you. So what’s your favorite sport?

Chad Michener:  Gee, I would say college football to watch. To play, I like to run as my primary mode of activity.

Scott Steele:  Favorite meal?

Chad Michener:  I would say steak, believe it or not.

Scott Steele:  And what’s the last nonmedical book that you’ve read?

Chad Michener:  The last one I read was a book called Driving Miss Norma, which was actually interesting, about a cancer patient. And we had visitors here at Cleveland Clinic that were the authors of that book, and they took their 90-year-old mother around the country in an RV and did a lot of visiting things for a lady that actually had an endometrial cancer, so an aggressive form. She chose that over doing treatment for her cancer, but kind of a fun read, a lot of things that they did, a lot of pictures. So that was actually a really fun, great book.

Scott Steele:  Fantastic. And tell us one thing you like about being here in Cleveland.

Chad Michener:  The thing I loved about being here, I did my fellowship here and actually chose to stay because there’s a lot of collaboration here. And even since I started 15 years ago, the Cleveland Clinic has grown tremendously. There’s a lot of great relationships here, a lot of colleagues that I work with frequently. And so I thought it would be a great place to work from a family standpoint. Cost of living is great, as you know from living here. And there’s really a lot of stuff to do, so it actually is quite a fun city to be in. And so we’re super glad that we stayed.

Scott Steele:  Well, that’s fantastic. And so for more information about ovarian cancer, please download our guide by visiting Cleveland, that’s Cleveland And to make an appointment with a Cleveland Clinic specialist, call (216) 444-6601. That’s (216) 444-6601. Chad, thanks for joining us on Butts & Guts.

Chad Michener:  Right. Thanks, Scott. Appreciate it.

Scott Steele:  That wraps things up here at Cleveland Clinic. Until next time, thanks for listening to Butts & Guts.

Overall Health and Mindfulness Improves Treatment Response: An Expert Explains

Dr. Sangmin Lee shares the benefits of meditation and yoga and explains how mindfulness can affect your overall health.

Dr. Sangmin Lee is a hematologist-oncologist specializing in blood disorders and blood cancers at Weill Cornell Medicine and New York Presbyterian Hospital.

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How about this one? A positive attitude and mindfulness can improve treatment response.

Dr. Lee:

Absolutely. Absolutely. Treatment for leukemia can be tough. Some of the treatment involves intense chemotherapy. Treatment for leukemia can involve stem cell transplant. And a key important aspect of treatment is being healthy and being optimistic about treatment, because a lot of treatment can have side effects, and side effects can be not as apparent if you are physically more active, and in a good state. So, I think that having a positive outlook is very, very important.


Quality of life issues are difficult for some people. How do you talk with your patients about their quality of life, and staying healthy during their treatment?

Dr. Lee:

So, quality of life is absolutely important. I mean, the whole point of treating leukemia and any other treatment is not only to address the leukemia, but also have good quality of life. So, when discussing treatment options, you always have to balance the quality of life and side effects versus potential benefits. So, that’s always on our mind when discussing potential treatment options, and how it impacts the quality of life. Throughout the treatment process, we always tell our patients that being active, and having a good quality of life, and having good nutrition, is absolutely important, because that’s a key aspect of treatment for leukemia.


What about meditation and yoga for coping with anxiety around cancer diagnosis and treatment? Mindfulness.

Dr. Lee:

Absolutely, absolutely. Those can help. Especially having leukemia, it’s very life-changing, so a typical way that patients are diagnosed with acute leukemia is patients live a normal life, and then they develop, all of a sudden, abnormalities. And they’re diagnosed with acute leukemia, and it can be very sudden. And it can be very difficult. So, that can understandably make patients have anxiety, and other issues.

And I believe that meditation, and yoga, and other exercises can absolutely help cope with this.


And there’s tons of resources for meditation and yoga out there, that are reliable.

Dr. Lee:

Yes. Yeah.


Yeah. Should patients regard yoga and meditation as part of their treatment, as part of their self-care, during this process?

Dr. Lee:

Absolutely, absolutely, if the patients are into meditation and yoga. Meditation is very harmless, and it can absolutely help in terms of guiding their mind through their treatment journey. Yoga is good if you’re physically able to do it. So, one caution is that, if you’re not someone who does yoga normally, then you should start off slow, and not push yourself as aggressively.

Does Cannabis Oil Have a Role in Cancer Treatment?

Is it just a trend or could cannabis oil truly have a role in cancer care and treatment? Dr. Sangmin Lee share his perspective.

Dr. Sangmin Lee is a hematologist-oncologist specializing in blood disorders and blood cancers at Weill Cornell Medicine and New York Presbyterian Hospital. 

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The use of cannabis oil is becoming prevalent. Does this have a role in cancer care and treatment?

Dr. Lee:

Absolutely. So, we use it for a lot of side effect management. So, cannabis can be helpful, in terms of appetite and nausea, for example. So, we often use it in conjunction to manage some of the side effects that patients can have throughout their treatment.

You should consult with your medical team, and of course, I should say that laws differ state by state, so it doesn’t apply to every state. But when it’s available, it can be a valuable addition.


Sure. Discuss that with your physician.

Sugar Feeds Cancer: Fact or Fiction?

Does sugar feed cancer? Dr. Sangmin Lee addresses the rumored connection between sugar and cancer.

Dr. Sangmin Lee is a hematologist-oncologist specializing in blood disorders and blood cancers at Weill Cornell Medicine and New York Presbyterian Hospital. 

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Okay, a little more fact or fiction, here. This is what we’ve heard from patients who have AML about cures, okay? Sugar feeds cancer, and severely restricting my diet will treat my AML.

Dr. Lee:

That’s not proven so far. There are some laboratory studies, especially with keto diets, showing some promise, maybe. But then it hasn’t been proven in humans, yet. The most important thing about AML treatment is actually nutrition. As patients go through AML treatment, it’s very important to stay healthy, and part of that is nutrition.

So, starvation, in general, is not recommended, because nutrition is so important, in terms of being able to undergo the treatment, as well as treatment visits, and everything. So, we recommend that nutrition is very important.

Are Clinical Trial Participants Monitored More Closely?

Dr. Sangmin Lee discusses the monitoring of clinical trial participants and the measures taken for patient safety.

Dr. Sangmin Lee is a hematologist-oncologist specializing in blood disorders and blood cancers at Weill Cornell Medicine and New York Presbyterian Hospital. 

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How about this next one? I am monitored more closely in a clinical trial.

Dr. Lee:

In some cases, it’s true. Clinical trials do have certain monitoring visits, in terms of doctor’s visits, laboratory tests, and physical exams.

The purpose of that is to make sure that it is safe. So, the purpose of monitoring closely, in a lot of cases, is for the patient’s safety. We are testing drugs in a lot of clinical trials, for which the complete safety profile, as well as efficacy profile, is not known. So, the purpose of closer monitoring is to make sure whatever we’re doing is safe, and if there are any unexpected side effects, then it allows us to address the side effects, as well. So, it’s mainly for patients’ safety.

Will Clinical Trials Cost You? The Facts.

Dr. Sangmin Lee reviews the financial impact associated with clinical trials, including a discussion of what expenses are covered for participants.

Dr. Sangmin Lee is a hematologist-oncologist specializing in blood disorders and blood cancers at Weill Cornell Medicine and New York Presbyterian Hospital. 

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All right, how about this one: I may have unexpected costs if I join a clinical trial.

Dr. Lee:

So, typically, that’s actually, usually not true, because how it works is that the clinical trial drugs, and that there may be extra procedures or visits associated with clinical trials.

And what usually happens is that the sponsor of the clinical trial provides the cost of the drug, intervention, and anything extra that are required for the clinical trial. So, in the end, the cost of participating in a clinical trial should not be any more than receiving standard care treatment.

In some rare cases, there may be stipends associated with the clinical trial, especially with travel. So, if you participate in a clinical trial, and you live far away, then you should ask to see if there is any stipends available, especially for travel.

Is It Safe? Breaking Down the Clinical Trial Process

The idea of a clinical trial can be intimidating and confusing for many patients. Dr. Sangmin Lee explains the phases of clinical trials, including the safety protocols in place to protect patients.

Dr. Sangmin Lee is a hematologist-oncologist specializing in blood disorders and blood cancers at Weill Cornell Medicine and New York Presbyterian Hospital. 

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What is the process for getting medicine to patients during clinical trials?

Dr. Lee:

So, clinical trials are basically what’s needed to prove that drugs work. So, a lot of times, we test drugs in a test tube in AML cell lines, and they show great promise. But just because a drug works in a test tube setting, doesn’t actually mean that it will work in humans, because human bodies are much more complicated. So, we need to test promising drugs in humans to make sure they are safe and effective.

And that’s what the purpose of clinical trials are. Once they demonstrate safety and efficacy, then a drug then gets to be approved, and is available commercially. So, that’s the purpose of clinical trials.

To be involved in clinical trials, what it involves is, basically, you have to meet a sort of criteria, called eligibility, because different clinical trials have different criteria for selection. So, we have to look into that. And then, once you fit an eligibility or selection criteria, then you typically undergo certain diagnostic tests to enroll on a clinical study. And then, you get whatever drug or intervention that is designed to test in that setting.

So, there are numerous steps to actually enroll in a clinical study.


And like you mentioned, there’s a long way between rat studies and human trials. What are the phases of clinical trials?

Dr. Lee:

So, there are three phases for clinical trials, commonly. There’s phase one, and phase two, and phase three. Phase one is the earliest part of the clinical trial process. So, goal of a phase one study is to make sure a drug is safe in a human. So, phase one studies are usually the first time that you are testing the drug in humans, and the main purpose is to demonstrate that it’s safe. So, typically, in a phase one study, typically, you test a drug at a lower dose or dose levels to demonstrate safety. What it means is that you’re enrolling a few patients at a time.

Once a drug is proven to be safe, then you move on to phase two, which is basically testing the drug in more patients. And the purpose of phase two is to get a preliminary assessment of how effective a treatment would be.

So, typically, a phase two study involves many more patients in that setting. And then, if a phase two study shows that a drug is very promising, then the drug may move on to phase three, where, basically, in phrase three, you are comparing one intervention or a drug compared to the standard of care. And, typically, in a phase three setting, a computer decides randomly which intervention you get, whether it’s an intervention or new drug versus standard of care. And standard of care may include either placebo or chemotherapy intervention, that is standard of care. So, it’s not always placebo in phase three.