Peritoneal carcinomatosis

gdpawel

Peritoneal carcinomatosis from ovarian cancer: chemosensitivity test and tissue markers as predictors of response to chemotherapy

Chiara Arienti (1), Anna Tesei (1), Giorgio M Verdecchia (2), Massimo Framarini (2), Salvatore Virzì (3), Antonio Grassi (3), Emanuela Scarpi (1), Livia Turci (1), Rosella Silvestrini (1), Dino Amadori (1) and Wainer Zoli (1)

Author Affiliations

(1) Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Meldola, Italy

(2) Department of Surgery and Advanced Cancer Therapies, Morgagni-Pierantoni Hospital, Forlì, Italy

(3) Department of Surgery, Bentivoglio Hospital, Bologna, Italy

Abstract

Background:

Platinum-based regimens are the treatments of choice in ovarian cancer, which remains the leading cause of death from gynecological malignancies in the Western world. The aim of the present study was to compare the advantages and limits of a conventional chemosensitivity test with those of new biomolecular markers in predicting response to platinum regimens in a series of patients with peritoneal carcinomatosis from ovarian cancer.

Methods:

Fresh surgical biopsy specimens were obtained from 30 patients with primary or recurrent peritoneal carcinomatosis from ovarian cancer. ERCC1, GSTP1, MGMT, XPD, and BRCA1 gene expression levels were determined by Real-Time RT-PCR. An in vitro chemosensitivity test was used to define a sensitivity or resistance profile to the drugs used to treat each patient.

Results:

MGMT and XPD expression was directly and significantly related to resistance to platinum-containing treatment (p = 0.036 and p = 0.043, respectively). Significant predictivity in terms of sensitivity and resistance was observed for MGMT expression (75.0% and 72.5%, respectively; p = 0.03), while high predictivity of resistance (90.9%) but very low predictivity of sensitivity (37.5%) (p = 0.06) were observed for XPD. The best overall and significant predictivity was observed for chemosensitivity test results (85.7% sensitivity and 91.3% resistance; p = 0.0003).

Conclusions:

The in vitro assay showed a consistency with results observed in vivo in 27 out of the 30 patients analyzed. Sensitivity and resistance profiles of different drugs used in vivo would therefore seem to be better defined by the in vitro chemosensitivity test than by expression levels of markers.

Journal of Translational Medicine 2011, 9:94 doi:10.1186/1479-5876-9-94

http://www.translational-medicine.com/content/9/1/94

gdpawel

Cancer Cytometrics More Accurate than Molecular Gene Testing
Clinical Trial Finds Personalized Cancer Cytometrics More Accurate than Molecular Gene Testing

In the first head-to-head clinical trial comparing gene expression patterns with Personalized Cancer Cytometric testing (also known as “functional tumor cell profiling” or “chemosensitivity testing”), Personalized Cancer Cytometrics was found to be substantially more accurate.

In a clinical trial involving ovarian cancer patients, patterns of gene expression identified through molecular gene testing were compared with results of Personalized Cancer Cytometric testing (in which whole, living cancer cells are exposed to candidate chemotherapy drugs). Four different genes were included in the molecular part of the study. The four genes were selected as those which researchers believe to have the greatest likelihood of accurately predicting individual patient response to specific anti-cancer drugs.

Study Results:

For two of the genes studied, there was no significant correlation between gene expression pattern and patient response. In other words, results for these genes were found to be meaningless. For the third gene studied, there was a 75% correlation between expression and patient response. This means that the gene was 75% accurate when it came to identifying an active drug for that patient. For the fourth gene studied, the accuracy in identifying an active drug was only 25%. In marked contrast, Personalized Cancer Cytometric testing was found by the researchers to be 90% accurate in identifying active drugs for ovarian cancer patients in this study.

Discussion:

Molecular testing – that is, testing for gene expression patterns – is widely studied and heavily promoted as a method to identify effective chemotherapy drugs for individual cancer patients. However, most studies of molecular testing carried-out to date show only modest correlation or no correlation between test results and actual patient response. In other words, much work remains to be done before molecular gene testing can be regarded as an accurate tool for chemotherapy selection. And yet in this, first ever, head-to-head study of test accuracy, Personalized Cancer Cytometrics was found to be highly accurate when it came to identifying effective drugs.

Comparing this study with previous studies:

Although this was the first head-to-head trial, the accuracy levels found in this trial for Personalized Cancer Cytometric testing are strikingly consistent with those documented in dozens of previous studies, published by respected cancer researchers around the world. In those studies, as in this one, extremely high levels of correlation (in other words, high levels of test accuracy) were found for Personalized Cancer Cytometrics.

Arienti et al. Peritoneal carcinomatosis from ovarian cancer: chemosensitivity test and tissue markers as predictors of response to chemotherapy. Journal of Translational Medicine 2011, 9:94.

gdpawel

gdpawel said:

Cancer Cytometrics More Accurate than Molecular Gene Testing
Clinical Trial Finds Personalized Cancer Cytometrics More Accurate than Molecular Gene Testing

In the first head-to-head clinical trial comparing gene expression patterns with Personalized Cancer Cytometric testing (also known as “functional tumor cell profiling” or “chemosensitivity testing”), Personalized Cancer Cytometrics was found to be substantially more accurate.

In a clinical trial involving ovarian cancer patients, patterns of gene expression identified through molecular gene testing were compared with results of Personalized Cancer Cytometric testing (in which whole, living cancer cells are exposed to candidate chemotherapy drugs). Four different genes were included in the molecular part of the study. The four genes were selected as those which researchers believe to have the greatest likelihood of accurately predicting individual patient response to specific anti-cancer drugs.

Study Results:

For two of the genes studied, there was no significant correlation between gene expression pattern and patient response. In other words, results for these genes were found to be meaningless. For the third gene studied, there was a 75% correlation between expression and patient response. This means that the gene was 75% accurate when it came to identifying an active drug for that patient. For the fourth gene studied, the accuracy in identifying an active drug was only 25%. In marked contrast, Personalized Cancer Cytometric testing was found by the researchers to be 90% accurate in identifying active drugs for ovarian cancer patients in this study.

Discussion:

Molecular testing – that is, testing for gene expression patterns – is widely studied and heavily promoted as a method to identify effective chemotherapy drugs for individual cancer patients. However, most studies of molecular testing carried-out to date show only modest correlation or no correlation between test results and actual patient response. In other words, much work remains to be done before molecular gene testing can be regarded as an accurate tool for chemotherapy selection. And yet in this, first ever, head-to-head study of test accuracy, Personalized Cancer Cytometrics was found to be highly accurate when it came to identifying effective drugs.

Comparing this study with previous studies:

Although this was the first head-to-head trial, the accuracy levels found in this trial for Personalized Cancer Cytometric testing are strikingly consistent with those documented in dozens of previous studies, published by respected cancer researchers around the world. In those studies, as in this one, extremely high levels of correlation (in other words, high levels of test accuracy) were found for Personalized Cancer Cytometrics.

Arienti et al. Peritoneal carcinomatosis from ovarian cancer: chemosensitivity test and tissue markers as predictors of response to chemotherapy. Journal of Translational Medicine 2011, 9:94.

Aggressive Surgery Best Option
Mayo Clinic Cancer Center researchers reported aggressive surgical removal of as much cancer as possible throughout the abdomen in ovarian cancer patients is the best option for most women. Results of the study are published in the January 2006 issue of Obstetrics & Gynecology.

"This study provides further evidence that surgery to remove as much tumor as possible at the initial operation is the best option for most patients," says William Cliby, M.D., Mayo Clinic gynecologic oncologist and lead investigator of the study. "It helps to define a topic that is often debated within our specialty -- the benefit of radical surgery for advanced ovarian cancer patients." Dr. Cliby says that data demonstrate many surgeons choose the more cautious route of less surgical intervention, and this results in shorter overall survival.

Dr. Cliby and his team of researchers found that aggressive surgery greatly improves survival rates for patients with the most severe disease spread. They also found similar five-year survival rates in most cases for patients undergoing radical and non-radical surgery, indicating to the researchers that aggressive surgery is not a significant risk factor, but instead aids in survival. In those patients with the highest volume of disease (carcinomatosis), the researchers found that radical surgery greatly improved the five-year survival rates (44% versus 17%).

Having a general preference towards maximum surgical intervention, Dr. Cliby and his fellow Mayo Clinic surgeons see the results of a survey conducted by the Society of Gynecologic Oncologists in 2001 as troubling, with 45.5% of respondents citing lack of evidence for improved survival as a primary rationale against performing aggressive surgical resection in specific cases of advanced ovarian cancer. The American Cancer Society predicts over 16,000 women in the United States will die from ovarian cancer this year, and Dr. Cliby's team hope their study will promote a trend toward more aggressive surgeries when warranted. "Our study showed a significant survival advantage when a more aggressive surgical approach is used," says Dr. Cliby. "Hopefully we'll see increased education and a movement towards a more uniform surgical management of ovarian cancer."

Dr. Cliby's team notes that while surgery is just one part of the treatment for advanced ovarian cancer, it is the one variable gynecologic oncologists treating this disease can most control. To improve the outcomes of this disease, they hope to see more research in resistance to chemotherapy, prevention of recurrent disease, and earlier detection.

This study's purpose was to estimate the effect of aggressive surgery on overall survival rates for ovarian cancer patients. The main outcome measures were residual disease after tumor reduction surgery, frequency of radical surgical procedures and five-year, disease-specific survival. Radical surgery procedures included diaphragmatic surgery, bowel resection, splenectomy or extensive abdominal peritoneal stripping or resection.

Because several other factors are part of the decision to perform surgery, especially more radical surgeries, Dr. Cliby's team also looked at risks related to age, preoperative medical condition and operative time. They found that residual disease and radical surgery were the only factors that consistently predicted survival.

The study cohort of 194 women was assembled from patients who underwent primary surgery for stage IIIC ovarian cancer at Mayo Clinic between 1994 and 1998.

Other Mayo researchers assisting in the study include: Giovanni Aletti, M.D.; Sean Dowdy, M.D.; Bobbie Gostout, M.D.; Monica Jones, M.D.; Robert Stanhope, M.D.; Timothy Wilson, M.D.; and Karl Podratz, M.D., Ph.D.

Source: Mayo Clinic

Kudos on the Mayo Clinic Cancer Center study of aggressive surgery being the best option for advanced-stage ovarian cancer patients.

Patients with ovarian cancer should undergo aggressive de-bulking surgery up front, prior to chemotherapy. It has long been observed that those patients whose tumors can be resected without any visible residual disease tend to live longer than those who are left with residual tumor after de-bulking surgery. Based upon this, up front, de-bulking surgery has become the standard of care.

Some researchers believe the reason for better survival for patients who could undergo complete resection without any tumor left behind is that these tumors are biologically less aggressive and would do better regardless of the type of treatment they receive.

Surgery is an integral part of the multimodality treatment of many cancers. In the case of ovarian cancer, proper patient selection will ensure the benefit of surgery for those who need it and avoid its morbidity and delay in the commencement of chemotherapy for those who are unlikely to benefit from it.

wanttogetwellsoon

gdpawel said:

Aggressive Surgery Best Option
Mayo Clinic Cancer Center researchers reported aggressive surgical removal of as much cancer as possible throughout the abdomen in ovarian cancer patients is the best option for most women. Results of the study are published in the January 2006 issue of Obstetrics & Gynecology.

"This study provides further evidence that surgery to remove as much tumor as possible at the initial operation is the best option for most patients," says William Cliby, M.D., Mayo Clinic gynecologic oncologist and lead investigator of the study. "It helps to define a topic that is often debated within our specialty -- the benefit of radical surgery for advanced ovarian cancer patients." Dr. Cliby says that data demonstrate many surgeons choose the more cautious route of less surgical intervention, and this results in shorter overall survival.

Dr. Cliby and his team of researchers found that aggressive surgery greatly improves survival rates for patients with the most severe disease spread. They also found similar five-year survival rates in most cases for patients undergoing radical and non-radical surgery, indicating to the researchers that aggressive surgery is not a significant risk factor, but instead aids in survival. In those patients with the highest volume of disease (carcinomatosis), the researchers found that radical surgery greatly improved the five-year survival rates (44% versus 17%).

Having a general preference towards maximum surgical intervention, Dr. Cliby and his fellow Mayo Clinic surgeons see the results of a survey conducted by the Society of Gynecologic Oncologists in 2001 as troubling, with 45.5% of respondents citing lack of evidence for improved survival as a primary rationale against performing aggressive surgical resection in specific cases of advanced ovarian cancer. The American Cancer Society predicts over 16,000 women in the United States will die from ovarian cancer this year, and Dr. Cliby's team hope their study will promote a trend toward more aggressive surgeries when warranted. "Our study showed a significant survival advantage when a more aggressive surgical approach is used," says Dr. Cliby. "Hopefully we'll see increased education and a movement towards a more uniform surgical management of ovarian cancer."

Dr. Cliby's team notes that while surgery is just one part of the treatment for advanced ovarian cancer, it is the one variable gynecologic oncologists treating this disease can most control. To improve the outcomes of this disease, they hope to see more research in resistance to chemotherapy, prevention of recurrent disease, and earlier detection.

This study's purpose was to estimate the effect of aggressive surgery on overall survival rates for ovarian cancer patients. The main outcome measures were residual disease after tumor reduction surgery, frequency of radical surgical procedures and five-year, disease-specific survival. Radical surgery procedures included diaphragmatic surgery, bowel resection, splenectomy or extensive abdominal peritoneal stripping or resection.

Because several other factors are part of the decision to perform surgery, especially more radical surgeries, Dr. Cliby's team also looked at risks related to age, preoperative medical condition and operative time. They found that residual disease and radical surgery were the only factors that consistently predicted survival.

The study cohort of 194 women was assembled from patients who underwent primary surgery for stage IIIC ovarian cancer at Mayo Clinic between 1994 and 1998.

Other Mayo researchers assisting in the study include: Giovanni Aletti, M.D.; Sean Dowdy, M.D.; Bobbie Gostout, M.D.; Monica Jones, M.D.; Robert Stanhope, M.D.; Timothy Wilson, M.D.; and Karl Podratz, M.D., Ph.D.

Source: Mayo Clinic

Kudos on the Mayo Clinic Cancer Center study of aggressive surgery being the best option for advanced-stage ovarian cancer patients.

Patients with ovarian cancer should undergo aggressive de-bulking surgery up front, prior to chemotherapy. It has long been observed that those patients whose tumors can be resected without any visible residual disease tend to live longer than those who are left with residual tumor after de-bulking surgery. Based upon this, up front, de-bulking surgery has become the standard of care.

Some researchers believe the reason for better survival for patients who could undergo complete resection without any tumor left behind is that these tumors are biologically less aggressive and would do better regardless of the type of treatment they receive.

Surgery is an integral part of the multimodality treatment of many cancers. In the case of ovarian cancer, proper patient selection will ensure the benefit of surgery for those who need it and avoid its morbidity and delay in the commencement of chemotherapy for those who are unlikely to benefit from it.

thanks...
Thanks for the research Ray.

I'm waiting to see whether I'll be offered an operation. I have already had many ops in the past but whether my surgeon will agree to do one to remove some structures and adhesions now I have cancer remains to be seen. Whether to have the op if it's offered is a close call because, as you have shown, it seems that there are better outcomes for those who undergo radical surgery. However, some researchers believe that those who do have the surgery and are left with little residual cancer are likely to be those who have a biologically less aggressive form of the disease anyway. I think a lot more research will need to be done. Meanwhile, I guess I'll just have to be hopeful that my course is the best one for the type of disease I have and that I'll be offered it in the first place.

Thanks again. Good wishes to you and your family.

gdpawel

wanttogetwellsoon said:

thanks...
Thanks for the research Ray.

I'm waiting to see whether I'll be offered an operation. I have already had many ops in the past but whether my surgeon will agree to do one to remove some structures and adhesions now I have cancer remains to be seen. Whether to have the op if it's offered is a close call because, as you have shown, it seems that there are better outcomes for those who undergo radical surgery. However, some researchers believe that those who do have the surgery and are left with little residual cancer are likely to be those who have a biologically less aggressive form of the disease anyway. I think a lot more research will need to be done. Meanwhile, I guess I'll just have to be hopeful that my course is the best one for the type of disease I have and that I'll be offered it in the first place.

Thanks again. Good wishes to you and your family.

Surgical Specimen Personalized Part Personalized Cancer Medicine
Correct, some researchers believe the reason for better survival for patients who could undergo complete resection without any tumor left behind is that these tumors are biologically less aggressive and would do better regardless of the type of treatment they receive, and that the removal of lymph nodes at the time of surgery may additionally contribute to a better outcome.

The line of reasoning frequently used to explain the value of surgery included five points. (1) surgery is thought to remove resistant clones of tumor cells and thus decrease the likelihood of the early onset of drug resistance. (2) the removal of large masses likely to be associated with poorly vascularized areas of tumor improves the probability of delivering adequate drug doses to the remaining cancer cells. (3) the higher growth fraction in better vascularized small masses enhanced the effect of chemotherapy. (4) smaller masses required fewer cycles of chemotherapy and thus decreased the likelihood of drug resistance. (5) removal of bulky disease enhances the immune system. Patients who present with a large mass are suffering because of that mass and they need that tumor out to relieve symptoms and to save life due to symptoms. It's important to deal with the bulk.

Sources:
Mayo Clinic
American Board of Surgeons
Society of Surgical Oncology

Some are recently finding out that small-cell lung cancer, the most aggressive lung cancer, there is an unusual therapeutic approach - surgery. The surgical specimen is the "personalized" part of personalized cancer medicine. Best wishes!

Greg

gdpawel

gdpawel said:

Surgical Specimen Personalized Part Personalized Cancer Medicine
Correct, some researchers believe the reason for better survival for patients who could undergo complete resection without any tumor left behind is that these tumors are biologically less aggressive and would do better regardless of the type of treatment they receive, and that the removal of lymph nodes at the time of surgery may additionally contribute to a better outcome.

The line of reasoning frequently used to explain the value of surgery included five points. (1) surgery is thought to remove resistant clones of tumor cells and thus decrease the likelihood of the early onset of drug resistance. (2) the removal of large masses likely to be associated with poorly vascularized areas of tumor improves the probability of delivering adequate drug doses to the remaining cancer cells. (3) the higher growth fraction in better vascularized small masses enhanced the effect of chemotherapy. (4) smaller masses required fewer cycles of chemotherapy and thus decreased the likelihood of drug resistance. (5) removal of bulky disease enhances the immune system. Patients who present with a large mass are suffering because of that mass and they need that tumor out to relieve symptoms and to save life due to symptoms. It's important to deal with the bulk.

Sources:
Mayo Clinic
American Board of Surgeons
Society of Surgical Oncology

Some are recently finding out that small-cell lung cancer, the most aggressive lung cancer, there is an unusual therapeutic approach - surgery. The surgical specimen is the "personalized" part of personalized cancer medicine. Best wishes!

Greg

The different genes studied in the genetic testing
The different genes that were studied in the molecular part of the above study were ERCC1, GSTP1, MGMT, XPD and BRCA1. These are putative drug resistance genes. ERCC and XPD are response elements for CDDP repair. BRCA1 is also a response element for DNA damage and part of FANC gene family (a genomic fidelity function).

GSTP1 is a detoxifying enzyme associated with thiol conjugation (alkylator resistance) while MGMT is the specific enzyme associated with the removal of temozolomide residues from DNA base pairs.

What the investigators did was to examine the "Target Now" types of targets and compare clinical responses against the results with functional analyses, establishing that when one measures the biology of the disease it provides a more robust prediction of response. The "driver" term is less operative as these genes are not causative of the disease but causative of drug resistance.

LaundryQueen

gdpawel said:

Surgical Specimen Personalized Part Personalized Cancer Medicine
Correct, some researchers believe the reason for better survival for patients who could undergo complete resection without any tumor left behind is that these tumors are biologically less aggressive and would do better regardless of the type of treatment they receive, and that the removal of lymph nodes at the time of surgery may additionally contribute to a better outcome.

The line of reasoning frequently used to explain the value of surgery included five points. (1) surgery is thought to remove resistant clones of tumor cells and thus decrease the likelihood of the early onset of drug resistance. (2) the removal of large masses likely to be associated with poorly vascularized areas of tumor improves the probability of delivering adequate drug doses to the remaining cancer cells. (3) the higher growth fraction in better vascularized small masses enhanced the effect of chemotherapy. (4) smaller masses required fewer cycles of chemotherapy and thus decreased the likelihood of drug resistance. (5) removal of bulky disease enhances the immune system. Patients who present with a large mass are suffering because of that mass and they need that tumor out to relieve symptoms and to save life due to symptoms. It's important to deal with the bulk.

Sources:
Mayo Clinic
American Board of Surgeons
Society of Surgical Oncology

Some are recently finding out that small-cell lung cancer, the most aggressive lung cancer, there is an unusual therapeutic approach - surgery. The surgical specimen is the "personalized" part of personalized cancer medicine. Best wishes!

Greg

Thanks for the info. I can't
Thanks for the info. I can't remember where I read this but somewhere online there is information about the greater likelihood of metastasis AFTER the primary tumor has been removed. This is what happened to me. The cancer became much more aggressive post-operatively and spread into my liver.

gdpawel

LaundryQueen said:

Thanks for the info. I can't
Thanks for the info. I can't remember where I read this but somewhere online there is information about the greater likelihood of metastasis AFTER the primary tumor has been removed. This is what happened to me. The cancer became much more aggressive post-operatively and spread into my liver.

Chemo-induced gene mutation
A chemo-induced gene mutation can happen when the original chemo received does not work (ineffective). The cancer comes back. When it does this, the cancer comes back more aggressively. The mutagenic effects (changes in form) of chemotherapy on a genetically-unstable tumor, drives the tumor into a state of more aggressive behavior. You might kill off a whole lot of cancer, only to cause a mutation in the remaining cancer, such that the remaining cancer behaves in a more aggressive fashion.

Cancers that are a product of these genetic mutations release cells from the usual controls of proliferation and survival, making them so much harder to fight it. Following this mutation, the cancer cells acquire the ability to proliferate without the normal restraints. As the cancer grows, it may infiltrate and destroy the surrounding tissue and metastasize by penetrating into blood vessels, lymph nodes and body cavities. Distant metastasis via the blood stream may affect virtually any organ (the lungs, bones, liver, adrenals and even the brain).

Anxious Kathy

gdpawel said:

Chemo-induced gene mutation
A chemo-induced gene mutation can happen when the original chemo received does not work (ineffective). The cancer comes back. When it does this, the cancer comes back more aggressively. The mutagenic effects (changes in form) of chemotherapy on a genetically-unstable tumor, drives the tumor into a state of more aggressive behavior. You might kill off a whole lot of cancer, only to cause a mutation in the remaining cancer, such that the remaining cancer behaves in a more aggressive fashion.

Cancers that are a product of these genetic mutations release cells from the usual controls of proliferation and survival, making them so much harder to fight it. Following this mutation, the cancer cells acquire the ability to proliferate without the normal restraints. As the cancer grows, it may infiltrate and destroy the surrounding tissue and metastasize by penetrating into blood vessels, lymph nodes and body cavities. Distant metastasis via the blood stream may affect virtually any organ (the lungs, bones, liver, adrenals and even the brain).

Thank you for the info!
My husband is battling secondary ppc from the appendix and is scheduled for the radical surgery. We have hope to see that 5 year survival. We continue to hope for more research for us and for others. We have signed up for clinical studies at Wake and hope it helps down the road! It is a cruel disease and amazingly he still is not in pain but discomfort has started so we are praying for a good surgery and recovery. Thanks again! Kathy