HIPEC after first line chemo

LorettaMarshall said:

"Worried..."HIPEC" delivered by hi-tech hospital is beneficial

Dear Worried Husband:

We can all understand your worry.  HIPEC is a good treatment, but not all hospitals are qualified to conduct that type of treatment.  This heated intraperitoneal is most effective for those who have had “optimal debulking”.  As noted in one of the references below, that would be tumors that have been reduced to 1 cm or less.  (That’s about ½ inch)  This treatment is often included as part of the “debulking” surgery, when things are favorable.  The University of Pittsburgh Medical Center conducts a vast amount of HIPEC treatments that are taking place today.  When I had my Cytoreductive surgery (CRS) I was hoping to be a good candidate.  But when I awoke, my Dr. David Bartlett, had decided not to perform it on me.  Naturally, I was disappointed to find that it was not done in my situation.  It could well have been that they were not able to reduce all the tumors in my abdominal cavity to ½ inch or less.  In any event, I trust his judgment.  But I note that those who are able to have this treatment live longer than those who only have IV chemotherapy.

Now I’m assuming that if HIPEC has been recommended for your wife, that a hospital has also been recommended.  And I am supposing that the surgeon and/or medical facility that performed your wife’s surgery did not have the necessary equipment or training to conduct this type of treatment?  So I have included several sites below, and highlighted information that should be helpful.  Now I must say that I am a realist, and accept the fact that not all of us are going to make it to some “ripe old age”.  We’re all too aware of the survival stats for different stages of Ovarian Cancer.  Nevertheless, I was personally pleased to read about a number of “3C with high grade serous ovarian cancer” patients that had beaten the odds and were still living 10 years after diagnosis!  So I had to list that one for a positive outlook.   Although my surgeon did not elect to perform HIPEC in my case, I am still blessed to be alive 4 ½ years longer than I ever believed I would be.  So here’s wishing you and your wife every success.  It confines itself to the abdominal cavity and kills many tumors too small to be picked up on any scan.   If your wife’s surgeon has recommended it, I would certainly “second” that recommendation. 

Loretta

Peritoneal Carcinomatosis/Ovarian Cancer Stage IV/neo-adjuvant chemo of Carboplatin/Taxol/Cytoreductive Surgery (CRS) aka “debulking” July 1, 2013

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1. https://csn.cancer.org/node/309344

“HYPERTHERMIC INTRAPERITONEAL CHEMOPERFUSION (HIPEC) TREATMENT. My post on the Peritoneal Cancer link – This consists mainly of videos by my surgeon, Dr. David Bartlett, UPMC relative to how and why HIPEC is used.  I believe your questions will be answered when you read/view this posting.

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2.http://upci.upmc.edu/about/

3.      https://www.cancer.gov/research/nci-role/cancer-centers/find/upci

______________________________________________________________________4.  http://www.sciencedirect.com/science/article/pii/S0090825816300671

Gynecologic Oncology - Volume 141, Issue 2, May 2016, Pages 260–263 -

“Characteristics of 10-year survivors of high-grade serous ovarian carcinoma…

1. Introduction

Ovarian cancer has extensive heterogeneity within and between histologic subtypes [1]. High-grade serous carcinoma is the most aggressive subtype and accounts for the majority of advanced stage cases [2]. Ten-year survival for all ovarian cancer is approximately 30–40% according to the SEER registry and other studies [3] ;  [4]. Long-term (LT) survival of women with high-grade serous carcinoma (HGSC) is low and often associated with completely resected disease (no gross residual). While many factors have been reported to have prognostic value for HGSC beyond the current FIGO staging system, most have limited value for patients with advanced stage disease [5] ;  [6]. Nonetheless, the use of intraperitoneal therapy in patients with microscopic and small volume residual disease after cytoreductive surgery has been associated with long-term survival [7]…

2. Methods

A multi-center research consortium was established between five participating academic centers: Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center, Cedars-Sinai Medical Center, Stephenson Oklahoma Cancer Center at the University of Oklahoma, and University of Iowa.

IRB approval was obtained locally at each center. Study criteria were established that included patients with a diagnosis of high-grade serous ovarian, fallopian tube, or peritoneal carcinoma with at least ten years of follow up from the date of initial diagnosis to the date of death or last follow-up. All stages of cancer were permitted. Diagnosis dates for patients in this study range from 1979 to 2005. Non-serous, borderline tumors and low-grade serous subtypes were excluded in addition to any patients with insufficient follow up data. Grade 2 tumors were excluded unless they were re-reviewed and met contemporary criteria for high-grade serous carcinoma…

3. Results - 3.1. Patient characteristics

 Across the five centers, 203 patients were identified as LT ten-year survivors and included in this study. Demographic and clinical characteristics of the study group are shown in the Table 1. All patients were diagnosed with high-grade serous carcinoma of the ovary, fallopian tube, or peritoneum at their respective institution. The median age of patients was 57 years (range 37–84 years). Twenty-eight patients (13.8%) were older than 70 years at the time of diagnosis. The majority of patients were white (88.7%) and diagnosed with stage IIIC (72.4%) disease at presentation…

 Of the 198 patients with available treatment information, 92.9% underwent primary cytoreductive surgery and 7.1% received neoadjuvant chemotherapy prior to interval cytoreductive surgery.  Of those who underwent primary cytoreductive surgery, optimal cytoreduction, defined as residual disease of less than or equal to 1 cm in maximum diameter, was achieved in 143 (85.6%) patients.

A complete gross resection to no macroscopic residual disease was achieved in 70 (47.0%) patients.

Ascites was present at the time of surgery in 103 (70.5%) patients. All but one patient (99.5%) received a platinum agent as part of their adjuvant or neoadjuvant treatment regimens.

Intraperitoneal chemotherapy was given to 38 (20.8%) patients, with most of these patients receiving IP treatment as part of consolidation therapy…

3.2. Treatment outcome

After a median follow up of 144 months, 88 (46.8%) patients did not develop recurrent disease after initial treatment. This group was characterized by a high optimal cytoreduction rate (93%, 78/84) and a low rate of neoadjuvant chemotherapy (6%, 5/88)…

 3.3. Unusual responders

Unexpected findings from this survey of LT survivors includes 15% of patients having suboptimal cytoreduction at the time of primary surgical resection, 11% of patients having a platinum free interval of < 12 months, and 53% of patients having recurrent disease, yet still surviving more than ten years after diagnosis. Other unusual features of LT survivors include four patients with suboptimal cytoreduction and a platinum-free interval (PFI) of < 12 months. All were diagnosed with stage IIIC disease and none of them participated in a clinical trial as part of their adjuvant therapy. Within the subset of patients who received neoadjuvant chemotherapy, 50% survived 10 or more years without recurrence, a proportion similar to the overall study population.

There were eight patients with stage IV disease who did not experience any recurrence of their disease after initial treatment. The median OS of these survivors was 131 months (range 122–204 months). All eight women had an optimal debulking with < 1 cm of residual disease, five at primary debulking and three at interval debulking surgery after neoadjuvant chemotherapy. Those that received neoadjuvant chemotherapy all received carboplatin and paclitaxel, ranging from three to six cycles…”

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5.       http://news.cancerconnect.com/types-of-cancer/ovarian-cancer/ovarian-cancer-overview/

“…Common Epithelial Tumors: Common epithelial cancers that start in the surface epithelium account for the majority of ovarian cancers and include the following types:

• Serous: This is the most common type of ovarian cancer and accounts for about 40% of common epithelial cancers. It occurs most often in women between the ages of 40 and 60…

  Because epithelial ovarian cancers begin deep in the pelvis, they often do not cause any symptoms until they are at an advanced stage. Furthermore, many of the symptoms of ovarian cancer are hard to differentiate from symptoms experienced by women who do not have ovarian cancer, such as back pain, fatigue, abdominal bloating, constipation, vague abdominal pain, and urinary symptoms.

  Because of the lack of specificity of early ovarian cancer symptoms, [2] the majority of women (roughly 70%) already have advanced cancer at the time of diagnosis. [3]      Ovarian cancer is often originally suspected in women when their physician finds an abnormal pelvic growth during an internal pelvic examination. Ovarian cancer may spread to the lining of the abdominal cavity and lead to the buildup of fluid inside the abdomen, called ascites. Ovarian cancer may cause symptoms such as swelling of the abdomen, pain, irregular bowel movements or difficulty breathing when fluid places pressure on the lungs…

  Following surgical removal and staging of ovarian cancer, a final stage will be given. A Roman numeral from I to IV describes the stage and a letter from “A” to “C” describes a sub-stage. All new treatment information concerning ovarian cancer is categorized and discussed by the stage…”

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• 6.  http://news.cancerconnect.com/types-of-cancer/ovarian-cancer/stage-iii-ovarian-cancer/

“…Cytoreductive Surgery

During cytoreductive surgery (also called debulking), physicians attempt to remove as much of the ovarian cancer as possible. Cytoreductive surgery is beneficial because it reduces the number of cancer cells that ultimately need to be destroyed by chemotherapy and therefore, decreases the likelihood of the cancer developing a resistance to chemotherapy.

Initial cytoreductive surgery in ovarian cancer is currently considered the standard of care because clinical studies have shown that patients who have had optimal cytoreductive surgery live longer and have a more prolonged time to cancer recurrence than patients who have had suboptimal cytoreductive surgery ...

Researchers are also continuing to evaluate the use of a second or interval cytoreductive surgery to be performed after the chemotherapy has had a chance to further decrease the amount of cancer.[1]…

Clinical trials have demonstrated that for patients with advanced stage ovarian cancer, treatment with combination chemotherapy regimens containing a platinum (Platinol® or Paraplatin®) compound prolongs the duration of survival and prevents more recurrences of cancer compared to treatment with surgery and non-platinum compounds. Current adjuvant chemotherapy typically consists of a taxane and a platinum compound administered every 3 weeks for 6 cycles.  Unfortunately, fewer than 20% of patients treated with a platinum compound and paclitaxel survive without evidence of cancer recurrence 5 years following treatment. Because many patients still experience recurrence of their cancer following standard therapy, some patients and their doctors consider participation in clinical trials evaluating new treatment approaches as their initial option.

Intraperitoneal Chemotherapy

Intraperitoneal (IP) chemotherapy delivers chemotherapy directly into the abdominal cavity, where there is the greatest number of cancer cells. The chemotherapy is administered through a large catheter that is placed into the abdomen during the surgery to remove the cancer. This treatment appears to be most effective if surgery or other therapy has already reduced the size of any remaining cancer deposits to less than 1 cm, or about half an inch (this is sometimes referred to as “optimally debulked”).

Among women with optimally debulked Stage III ovarian cancer, a phase III clinical trial compared treatment with intravenous (IV) chemotherapy alone to treatment with both IV and IP chemotherapy.

Women who received both IV and IP chemotherapy survived more than a year longer than women who received only IV chemotherapy, but also experienced more severe side effects such as fatigue, pain, and low blood counts.[2]

According to a statement by the American College of Obstetricians and Gynecologists, “the decision to use IP chemotherapy must be individualized.”[3] The combination of IV and IP chemotherapy appears to improve survival among women with optimally debulked Stage III ovarian cancer, but at the cost of increased side effects…” ____________________________________________________________

7.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745605/

OVARIAN LOW-GRADE AND HIGH-GRADE SEROUS CARCINOMA: Pathogenesis, Clinicopathologic and Molecular Biologic Features, and Diagnostic Problems

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8.      http://www.healthline.com/health/cancer/ovarian-cancer-outlook#overview1

The Outlook For Ovarian Cancer: Prognosis, Life Expectancy And Survival Rates By Stage

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9.      http://www.cancernetwork.com/oncology-journal/intraoperative-hyperthermic-intraperitoneal-chemotherapy-patients-advanced-ovarian-cancer

“…Most studies of IP chemotherapy in ovarian cancer have involved cisplatin, because of positive results with this agent in murine models and more experience with it as a systemic therapy. However, recent prospective studies were able to demonstrate the feasibility of IP carboplatin application, [17, 18] which is an appealing alternative to cisplatin because of its lesser side effects, especially less polyneuropathy and nephrotoxicity.

HIPEC: Rationale

In recent years, a new form of IP therapy has emerged for patients with ovarian carcinoma: intraoperative hyperthermic IP chemotherapy (HIPEC). Many investigators are now evaluating and conducting critical discussions of the role and the rationale for this delivery technique, which requires intraoperative perfusion machines, elaborate logistics, and a high degree of organizational effort. It is still unknown whether HIPEC is associated with an improved survival that would justify the effort involved, but there are several potential advantages that make it a promising therapeutic option as part of a multimodality treatment:

• A high volume of chemotherapy can be delivered, and a homogenous distribution can be achieved. This is often not practical in conventional IP therapy, because of abdominal distension and pain, but it is feasible in HIPEC, since the patient is under anesthesia.

• There is no interval between cytoreduction and chemotherapy. The cytotoxic therapy is applied at the time of minimal disease manifestation, and there are no adhesions that might alter the distribution of the drug.

• Hyperthermia has a pharmacokinetic benefit. Several studies have convincingly shown that hyperthermia can increase both the tumor penetration of cisplatin [ 33] as well as the DNA crosslinking.[34]

• High concentrations of chemotherapy can be achieved in the intraperitoneal compartment with low systemic exposure—in a single intraoperative treatment…

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Loretta,

Thanks for the detailed response!

The facility my wife had surgery does conduct HIPEC. When I asked my wife's GynOnc about why he did not consider HIPEC during initial surgery he explained that there was an entry into the chest cavity when resecting her diaphragm which prevented using HIPEC.  

He believes since her cancer responds well to chemo (CA125 dropped exponentially after first infusion and is now 18 after the second infusion) using HIPEC after the completion of 6 IV therapies could benefit her greatly.

I read that HIPEC during debulking can be really difficult on the patient having gone through a huge surgery and having to deal with the side effects of the heated chemo. Therefore I think having HIPEC (closed abdomen technique) a month after her final IV chemo treatment may not be a bad idea. I understand there is concern about the scar tissue/adhesions from the surgery preventing absorption of the chemo drugs but I guess we're going to hope remaining cancer cells are not hiding behind those scars. In any case we will need a second, third opinions before going ahead with it.

Re: IP chemo I came accross this:

http://www.ascopost.com/issues/may-10-2016/intraperitoneal-chemotherapy-in-question-in-ovarian-cancers/

"Dr. Walker reported, intraperitoneal therapy did not confer a statistically significant progression-free-survival advantage over intravenous therapy alone"

Interesting.