Recurrent ovarian cancer

Unfortunately, patients with ovarian cancer often have their disease recurred.   As I discussed earlier, we divide the patients into platinum sensitive (have not seen carboplatin or cisplatin in the last 6 months) or platinum resistant (resistant to carbo or cisplatin).   The prognosis is better with platinum sensitive disease.   The treatment usually consists of doublet chemo (2 agents) rather than single agent based on ICON4 study.   The most common combination would be carboplatin and paclitaxel (Taxol) since ICON4 study showed that this combination has survival advantage compared to other platinum based chemo.   Other choices are carboplatin + Doxil or Carboplatin + Gemzar (please note that none of these have survival advantage in comparison to their control arm).

In platinum resistant, we don't use cisplatin or carboplatin.  But paclitaxel, doxil, topotecan, oral etoposide (VP 16) are active.   Recently, the West Clinic published a study using abraxane and avastin on patient with platinum resistant which showed about 50% response rate.  To the best of my knowledge, this is the highest response rate ever documented in medical literature.

Reference:

Phase II clinical trial of bevacizumab with albumin-bound paclitaxel in patients with recurrent, platinum-resistant primary epithelial ovarian or primary peritoneal carcinoma.

Tillmanns TD, Lowe MP, Walker MS, Stepanski EJ, Schwartzberg LS.

Gynecol Oncol. 2013

Using plain water to kill ovarian cancer

Ovarian cancer is the 2nd most common gynecologic cancer in the United States with the highest mortality in all-gynecologic cancers.   Optimal removal of most tumor during initial surgery has been shown to improve survival rate.  The presence of exfoliated ovarian cancer cells in the peritoneal cavity after ovarian cancer debulking surgery is well recognized.  These cells are viable and can grow back again.

We have just completed research showing plain water killed these cancer cells effectively.   We grew ovarian cancer cells in plates.  Then we bathed them in normal saline (same concentration as plasma/blood).   In this concentration (we call it isoosmolar), cancer cells continue to grow.   Then, we place some of these cells in water for 30 minutes.   The water, which is hypoosmolar (less salt concentration), diffused into the cancer cell wall and ruptured the cancer cells.   

We are currently writing this research paper and will submit for publication.   Now, we cannot use this finding yet on patients.  We need to go thru multiple studies in animals and human before we could use it.   But my prediction is to use water into abdomen after ovarian cancer surgery may improve survival.   Currently, we do the same thing using intraperitoneal chemotherapy.  I think water would be less toxic than chemotherapy in patients.  lets keep our finger cross.

Estimating risk of ovarian cancer

We have our research paper just been accepted for publication by the Archieve of Obstet and Gynecol (will be on line and printed version in a few months).   Our study included 324 patients undergoing adnexal/ ovarian mass surgery were recruited into the study. All study patients had a preoperative CT scan and serum CA-125 test. CT scan abnormalities included any solid tumor components, ascites, and pelvic or abdominal lymphadenopathy and omental caking.   There were 225 (70%) benign and 99 (30%]) malignant ovarian masses. Using logistic regression with the area under the curve of the receiver operating curve of 82%, the cancer probability was determined by the equation

e^{-3.6372 + 0.0306 * (A) + 0.001 * (B) + 0. 876 * (C)+1.551 * (D) + 1.7377 * (E) + 2.76 * (F)}

 1+e ^{-3.6372 + 0.0306 * (A) + 0.001 * (B) + 0.876 * (C) + 1.551 * (D) + 1.7377 * (E) + 2.76 * (F)}

where A = age, B = CA-125, C = solid adnexal mass is 1 and cystic is 0, D = ascites is 1, E = omental caking is 1 and absence is 0,; F = node size > 1 cm is 1 and < 1cm no is 0 value. The natural logarithm e is a constant [2.718281828]. For example, for a woman of age 60, CA-125 = 50 U/ml, with solid adnexal mass, ascites, omental caking, and lymphadenopathy, the probability is 0.994. Hence, this woman has a 99.4%  probability of having cancer.

I wish to caution that our study is still preliminary.  This paper showed a mathematical formula could be used in combination with CT scan finding to estimate risk for ovarian cancer.

Reference:

Santoso JT, et al.  CT adnexall mass score to estimate ovarian cancer.  Arch Gynecol Obstet. 2014

What are the risk factors for getting ovarian cancer?

Ovarian cancer is often detected late (stage III and IV) since we do not have effective screening test for it.  As a result, many patients with ovarian cancer died from the disease.  Some of my patients and their family ask me about risk factors that may increase their of ovarian cancer.  These risks may include

• Older age: ovarian cancer is thought to arise from frequent ovulation.  More ovarian ovulation results in more damage-repair of ovarian cell layer.  Some of the cells may mutate into cancer with time.  Thus, older age is the main risk factor for ovarian cancer
• Having one or more relatives with ovarian cancer: you may have BRCA genes or other genes that may make you susceptible to cancer.
• Having abnormalities in a gene, called BRCA1 or BRCA2.  BRCAs are tumor suppressor genes.   These genes make proteins that monitor and suppressor mutation which then lead into cancer.
• Having genes that are linked to hereditary nonpolyposis colorectal cancer (also called Lynch syndrome).  This mismatch repair genes responsible to multiple cancer mutations that lead to cancers in ovary, colon, uterus, etc.
• Never being pregnant: that means you ovulate more.
• Being overweight: may relate to excess estrogen level.

Some factors can reduce your risk of developing ovarian cancer, including:

• Using hormonal methods of birth control (pills, patch, vaginal ring, injection): these reduces the number of ovulation.  Some studies suggest 50% reduction in ovarian cancer by taking birth control for a few years.
• Being pregnant, breastfeeding: reduce your life time number of ovulation
• Having your tubes tied to prevent pregnancy: we think this is related to detecting any abnormalites/precancerous lesion during the tubal ligation procedure or some other unknown effect.
• Having your uterus or ovaries removed: self explanatory.  Although you may not get ovarian cancer since your ovaries have been removed, but you may still get peritoneal cancer (similar cells to your ovary that line entire internal abdominal and pelvic cavities).

excessive sugar may decrease your life and increase risk of cancer

There have been some interesting observational studies about excess calorie/sugar intake that correlates caloric restriction with longer life span.  Most of these studies were in animals such as mice.   Another observation was during the great depression, average life span was increased by 6 years than what expected - postulated to decrease food intake (except those stories about people committed suicide after losing their life saving in stock market).  

 

One common factor in animal and human studies was a protein called IGF1 (insulin growth factor 1) which is increased in response to our eating.  IGF1 seems to promote cell growth which is important in cell repair but excess of it may also induces cancer growth.

 

The fastest way to reduce IGF1 is by fasting.   I do not recommend fasting unless you are under your doctor's supervision.  However, I suspect that reducing overall amount of calorie/sugar intake will reduce excess IGF1 production.  Sugar/calories were hard to come by when we were roaming in the African prairie million of years ago.  Now, you just have to stop at your gas station and get a large cup of soda.  

 

My patients often told me that they do not eat much - in fact some of them just eat once or twice a day.  However, when I reviewed their food diary, we found that they ate mostly the wrong things (high calorie food).  My recommendation is to discuss with your physicians on how much calorie should you eat per day and stick to it.   In general, we eat more calories than we should.

PS: please read on my previous blog about exercise as well.  I am convinced that eating less calorie and more exercise are the most mundane advice I could give you but also the most effective in getting you healthier and live longer.

How do I treat my anemia during chemotherapy

Anemia (low red blood cells) have many causes.  During chemotherapy, it is usually due to suppression of your bone marrow (organs that make red blood cells).  Cancer also releases chemicals (cytokines) that can suppress your kidney from making erythropoetin (protein that induces your bone marrow to produce red blood cells).   In most of my patients undergoing active chemotherapy, iron deficiency anemia is not common.

Most anemias from cancer or chemotherapy are treated with blood transfusion.  Blood transfusion can rapidly replenish your blood and make you feel better quickly.  But blood transfusion has risks such as transfusion reaction, infection (HIV, hepatitis, etc) and others.   With advancement of testings, blood transfusion risks have decreased markedly.   In some selected cases, artificial erythropoetin may be given.  There are some studies that suggest giving erythropoetin may induce blood clot and cancer growth.  Thus, discuss with your oncologist before hand.

Reference:

- Santoso JT. Saunders B, Grosshart K.  Massive blood transfusion in obstetrics & gynecology.  Obstet Gynecol Surv. 2005 Dec;60(12):827-837

- Santoso JT. Lin D, Miller DS. Transfusion medicine in obstetrics and gynecology. Obstet Gynecol Surv 50(6): 470-481, 1995