26 yrs, low grade serous Adenoca of ovary

Summary:

26 yrs, low grade serous Adenoca of ovary, treatment options?

26 yrs, low grade serous Adenoca of ovary

Nikhilesh Patil 13 Apr 2011 19:39

Dear all, interesting case
26 yrs young lady,
Jan 2009: Presented with Ascites: was found to have ovarian tumor(9cms): Surgery- oophorectomy, uterus left behind in situ (patient wants her own baby). Path: Serous Borderline Tumor. Ca-125 =88 prior to surgery.
Nov 2010: Abdominal recurrence on imaging:Complex cystic and solid masses located within the pelvis overall (combined) size of all of these lesions is approximately 7.3 x 6.7 x 9.0 cm (sag x TV x AP), anterosuperior to the urinary bladder with a single one identified within the subcutaneous fat of the anterior lower abdomen. There is also an isolated lesion seen within the right adnexa. The enhancing/vascular nodular components make these consistent with tumour recurrence.
Feb 2011: Interventionist did a guided biopsy: Recurrent Serous Borderline Tumor.
March 2011, de-bulking surgery: Path: Low Grade Serous Adenocarcinoma.

Chemo Vs RT? Role of Chemo in low grade serous adenoca ? If RT, how do we do that, ? Whole Abdomen (patient has uterus in situ and wants her own baby, has tried IVF with 3 futile attempts in 2009-2010).

What is the treatment of choice here ?

Last edited on 14 Apr 2011 03:38 by Nikhilesh Patil Show more

Re: 26 yrs, low grade serous Adenoca of ovary

Rohit Malde 16 Apr 2011 17:21

Hi all, I m back …..

Borderline Serous Ovarian tumours are a heterogenous group of tumours, if they are restricted to ovary, the prognosis is excellent, while those with invasive peritoneal implants have poor prognosis. (Longacre et al, 2005).

The mainstay of treatment here is Surgery… Maximal cytoreduction is the predominant prognostic factor for the overall survival. Rest all is experimental and unproven.

There is no good evidence for any role of RT, and in view of her age = 26, one would usually like to avoid it for fear of second malignancy, as this lady would have a reasonable 5 yr survival between 55-75% (WHO , 2003).

Some clinicians wait for the third relapse and then treat with chemotherapy, while some select their patients at 2nd relapse, looking for poor prognostic factors, like ( suboptimal resection, invasive peritoneal implants) or factors like patient anxiety and preference.

Borderline tumours should be confirmed by at least 2 different pathologists.

Most commonly offered chemotherapy = Single agent carboplatin (AUC =6) x 6 #.
(Level 3 evidence for this approach).

Nikhilesh, the above approach mentioned was for recurrent Borderline tumours,
Now if i get it right, this lady has had a transformation from Borderline to Malignant (low grade).
She needs to be staged, she is at least stage IIIb if all disease confined to pelvis, and possibly IIIc if disease outside pelvis.

Std Mgt would be to offer Adjuvant chemo with either Single agent Carboplatin Vs Carboplatin + Paclitaxel.
(Level 1 evidence)
Again no role of RT, apart from clinical trials ..

Rohit Malde

Re: 26 yrs, low grade serous Adenoca of ovary

Nikhilesh Patil 17 Apr 2011 02:37

Welcome back Rohit and thanks for your input, she is Stage IIIC and the tumor board recommendation is Chemotherapy however the MO said the role of chemo in low grade tumor is not defined so the discussion of WAR came in, agreed its not a standard yet http://www.ncbi.nlm.nih.gov/pubmed/21276234
Re second malignancies: Very interesting observation from the SEER data base http://www.ncbi.nlm.nih.gov/pubmed/21454129 . We always blame RT but thats not the case

Last edited on 17 Apr 2011 02:42 by Nikhilesh Patil Show more

Re: 26 yrs, low grade serous Adenoca of ovary

radtuxabhishek 17 Apr 2011 04:34

Yes; the secondary cancer issue is rather overblown. Although I agree broadly to what Rohit has mentioned, but would it possible for instillation of P³² in this unfortunate lady? As far as I understand, that is to be attempted only if the peritoneal metastases is evident.

(Off topic: )One more thing. I personally feel that Whole Abdomen Radiation is rather underused in the IMRT era and we should improve our thought process beyond the 'moving strip technique".

---

Reality is merely a persistent illusion

Re: 26 yrs, low grade serous Adenoca of ovary

Nikhilesh Patil 18 Apr 2011 18:00

P-32 is used in select centres, we do not have that at our centre. I agree we should look more into IMRT/Helical Tomo/Rapid Arc for Whole Abdomen RT, infact Germany is way ahead and is conducting Phase II trial, there Phase I data is very promising.

Re: 26 yrs, low grade serous Adenoca of ovary

Rohit Malde 19 Apr 2011 19:35

There are few trials and interest in intraperitoneal chemotherapy, and P-32 is also an attractive option which few centres are looking into.

With regards to WART, the reference nikhilesh provided, was for pts who recd adjuvant chemo, and they further received consolidation WART.
WART has been used in few selected centres since 1980 but only as research tool / trial setting. I personally do not think, GOG, RTOG or these ICON groups would ever conduct an ovarian cancer trial looking into radiotherapy.
If i m not mistaken they have conducted early trials and gave up this concept.
These groups are the world leaders who have changed practice internationally.
Ph 2 trials dont mean std practice. and a ph 3 trial would involve at least 1000 pts minimum. Hence i would nt get excited about WART for at least another decade or 2, and if a trial does have positive trial, internationally ppl would wanna seek another confirmatory trial. You know what i m saying here……
With the explosion of newer agents, like EGFR , TKIs, MTOR inhib, kras, PI3K inhibitors, PARP inhibotrs, and god knows what else….. do you guys really believe RT has any chance to survive or even emerge…….. look at the next 10-20 yrs ahead of you.
RESERVE the sharp Radiotherapy cutting edge for something else….

Nikhilesh the article on 2nd malignancy says of 3266 (2862-3670) excess second solid cancers that could be related to radiotherapy, that is 8% (7-9) of the total in all radiotherapy patients (≥1 year survivors) and five excess cancers per 1000 patients treated with radiotherapy by 15 years after diagnosis.

I ve got no clue what these mean. Moresoever, what about the liquid cancers (lymphomas and leukemias).
Does Radiotherapy increase risk of those ? , if so were they taken into account.
Its a database at the end of the day… it gives you whatever you feed in the database.
You miss one patients foillowup, you potentially miss the chances of recording an event.
Database spans from 1973 to 2002, over last 37 yrs , we have more effective agents, and have potential more long term survivors…. was chemoradiotherapy or any of the std things we do, known then…. NO
Look at the patient population they chose…they left out Hodgkins i presume for a reason…
but anyways …nice publication for the cv for the authors…

Its difficult, what you routinely quote to your patients, the risk of 2nd malignancy ? ?
It proportionately increase over time.
risk at 20 yrs ?
risk at 30 yrs ?
risk at 50 yrs ?
Obviously this is relevant only for young patients,

Re: 26 yrs, low grade serous Adenoca of ovary

Santam Chakraborty 20 Apr 2011 01:01

Hi Rohit,
Nice to see you back. I have been off from Isocentre for quite some time too but this discussion drew me in. The evidence for these biological agents is actually worse than WART which has been in use before chemotherapy and has never been proven "ineffective". Its the potential risk of toxicity that WART has that lead to Chemotherapy taking over. The role of WART is not going to be in exclusion of these biological agents and chemotherapy and I think we are doing ourselves a big disservice by ignoring them from our trials. Going by the nature of ovarian cancer and the fact that it requires higher doses than what can be delivered safely for reliable eradiation combination with a radiosensitizing biological agent is going to be the future. I simply dont believe in the hype behind biological agents for the simple reason that Cancer is not a beast that can be trained by a single pathway attack. If anything cancer is the epitome of evolution and has achieved what every cell in body tries to achieve (unlimited replicative potential). To become malignant a cell evades god knows how many checks and balances that have evolved since unicellular organisms came together to form multicellular colonies. We need and will continue to need the randomness that radiation provides in form of targetting. The matter of delivery of radiation is of course another point all together. Unfortunately unless we radiation oncologists loose our timidity and incompetence we will see medical oncologists dealing with radiopharmaceuticals in the near future.
As far as trials go trials on TKIs and PARP inhibitors have been initiated on more tenuous potential benefits thanks to big purses of the pharma industry. IF we had that kind of industry backing we would see RT being tried in every cancer in trials.
That said I do agree there is no role in "routine" clinical practice but at the same time its our duty as physicians to tell the patients about the clinical trials. An off hand search produced two ongoing accruing protocols in Germany which we as radiation oncologists should actively help. Medical oncologists will recommend trials much more than we as ROs do simply because they are more aware? I wonder.

---

Re: 26 yrs, low grade serous Adenoca of ovary

Nikhilesh Patil 20 Apr 2011 02:52

Thanks for your inputs Rohit and Santam,
I tend to agree with both of you. WART was given up becoz of toxicity issues and chemo took over which at that time was a simpler and effective approach. All the new agents always sound very interesting but in reality very few that reach clinics and those which reach are prohibitively expensive. I dont practice chemo but you may have assess to some of these agents in UK.
For my case, Iam not saying Chemo should not be offered, infact it is being offered but the treating GYNONCO and MO both asked me if we are capable of doing WART to consolidate response. I gave her all the available paper to read, the problem is we do not have a formal clinical trial testing WART. If this patient comes back saying she wants to give it a shot then we RO's will seriously need to consider this option.

Also we as a group need to think of generating new evidence rather than just adding to the experience later on.

Re:

radtuxabhishek 20 Apr 2011 02:58

The discussion has veered off towards WART as intended.

Couldn't agree more with Santam as above. Generically speaking, molecular agents are definitely a significant advantage compared to the "primitive chemotherapy" for we have known more about the molecular mechanisms this way. Nevertheless, targeting a single pathway is fraught with it's own set of issues.

I wouldn't be surprised if "combination molecular therapy" is actively promoted in future.

And then again, these agents have no impact on overall survival…..but thats another controversy.

I couldn't agree more with Rohit; even if you miss a patient, that's a "loss of an event".

I personally believe that secondary cancers is an overblown risk but at the same time it is hard to ignore the "low dose cloud". In what way does it fundamentally affect the patient?

Is it not that the cancer patients are predisposed towards secondary carcinoma risks over a period of time? But how much? How can this really be quantified?

With regards to the older "WART" studies, I would give them a huge benefit of doubt as far as the results are concerned. If you ask a surgeon to operate with a blunt scalpel, it is impossible to judge his "operating standards" because of sub-optimal tools. This does not mean that surgeon is incompetent.

Similarly for Radiation; outmoded machinery with lack of knowledge about long term effects on OAR's (which are still in process of being documented), does NOT mean that Radiation is "ineffective". The very essence of radio-pharmaceuticals is it's "targeted approach". So there. But then, that's opening up a minefield again.

Medicine, indeed, is an imperfect science, still.

---

Reality is merely a persistent illusion