treatment of inoperable T4 buccal mucosa cancer

treatment of inoperable T4 buccal mucosa cancer

Swarupa Mitra 10 May 2011 06:44

Hi,
i would like opinions regarding a case of buccal mucosa, T4N0 M0.
Middle aged patient presents with a buccal mucosa tumour, invading RMT and the mandible, inoperable even after 3 cycles of NACT.
What would now be the best course of action, considering a locally advanced tumour in a young patient with bone and skin involve ment.
Such cases are very comon in all cance OPDS.

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Dr. Swarupa Mitra
Consultant Radiation Oncologist.
Artemis Hospital gurgaon
09812399708,9717041602

Re: treatment of inoperable T4 buccal mucosa cancer

Rohit Malde 12 May 2011 19:29

Quite a interestin discussion and varying viewpoints from all members.
Few points from my end….

1. Why was this patient offered NACT with Cisplatin + Taxane ?

The std international regime has been Cis + 5FU, and over the last 4-5 years, based on TAX 324 study, there is a survival benefit of TPF (Docetaxel + Cisplat + 5 FU) Vs PF (Cispl + 5FU).
The response rate were (67.8% versus 53.6%) p=0.006.

http://theoncologist.alphamedpress.org/cgi/content/full/12/8/967#SEC4

2. I agree with Prasads comments with regards to PS and high dose Pall RT Vs CTRT.

3. Cisplatin
When used as induction chemo, we exploit the ability of this drug damaging DNA crosslink,
while in CTRT, we exploit its radiosensitising property in addition.
Hence using Cisplatin in such scenario would still impart some value if intention is RADICAL
If we respect the patients pocket, she probably cannot afford Cetuximab as earlier suggested, but is
certainly a valid option.

4. There are so many treatment options, ranging from palliative to radical, and from idealistic to realistic.

5. At the end of the day, this lady should be counselled, there is indeed a high probability that she would relapse.
My best estimate for her 5 yr OS would range 15-25% provided i have IMRT, Chemo and have Radical Intent.

Re: treatment of inoperable T4 buccal mucosa cancer

Santam Chakraborty 13 May 2011 02:08

Head neck cancer always invokes passionate discussion on Isocenter.
THE real question that needs to be asked is why NACT at all (not why taxane based NACT).
The TAX trials were designed to answer the question that addition of taxane gives better outcomes over PF or not — that is the only thing that can come out of that study any thing else is dangerous extrapolation. Oh the fact that only 14% were OC patients immediately makes any application of these findings in this patient questionable.
The trial that was designed to answer the question if NACT adds anything over concurrent radio-chemotherapy is the one conducted by Paccagnella 2010 which is a Phase II trial and shows no difference in terms of survival. Infact the Cochrane review has the conclusion that based on "EVIDENCE" alone NACT cannot be recommended to be included in the treatment before CRT. http://www.update-software.com/BCP/WileyPDF/EN/CD006386.pdf
People tend to look at the Paccagnella article as proof positive that NACT gives better results than CRT based on the better response rates but frankly their concurrent chemotherapy regimen is not standard (CDDP + 5Fu at weeks 1 and 6 with total CDDP dose = 160 mg/m²). I am pretty suire given this inferior chemoRT arm their phase III trial is going to come out positive. Of course a detailed perusal of the study shows that their assessment of CR was faulty being conducted at 6 weeks when 5 patients shifted from CR to PR in the follow up (which is like Duh !!! - every RO knows that).

I would recommend strongly going through the chocrane review which clearly shows that NACT doesnot give better results over LRT alone. In particular there is no convincing evidence that it increases the operability (which i presume was the premise behind the use of this regimen).

Another interesting read for ROs who are apologetic for NACT is this very very well written editorial by Jeremic et al (http://jco.ascopubs.org/content/26/10/e1.full) for NSCLC. The phenomenon of accelerated repopulation after NACT is known for a long time.. its a different matter that sanofi aventis is "helping" the oncologists to reinvent the wheel over again!!

The real reason that this patient is now not going to have any response after RT is the accelerated repopulation thanks to the NACT. If there is any way of making the RT better it is by altered fractionation .. please do consider hyperfractionation for her..

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Last edited on 13 May 2011 02:19 by Santam Chakraborty Show more

Re: treatment of inoperable T4 buccal mucosa cancer

radtuxabhishek 13 May 2011 02:35

I wonder why we forget the BASIC RADIOBIOLOGY of the disease. NACT leads to accelerated repopulation. Which means that RESISTANT CLONES are SELECTED.

NACT is STILL NOT INDICATED in ORAL CANCERS. The only proof of NACT in Head and Neck having worked was in antiquated Veteran's Laryngeal Trial which "prevented" surgery (or delayed the salvage) conducted well over 20 years ago. I wonder how has this been extrapolated to other subsites (my imagination refuses to wander there).

For the sake of argument, Cetuximab IS NOT MAGICAL drug. Molecular pathways (it has been mentioned in the previous forum posts many times) is very deceptive. EGFR Blockade is NOT the solution in face of resistant clones which would have MANY alternative pathways to resist apoptosis.

These resistant clones HAVE ALREADY been PRE-SELECTED by NACT.

TAX 324 trial (and others exploring the use of NACT/Taxanes) have been HEAVILY criticized in various forums earlier for the lack of standardized definition of "cure rates".

In my opinion, it is justifiable to base treatment decisions on high quality evidence accrued from properly conducted phase III trials or pooled analysis. Justifying a neo-adjuvant approach on basis of poorly conducted phase II (or stunted statistical evaluated) trials is NOT justified in the best interests of the patient. Most of the patients are unlikely to complete their radical chemoradiation, or radiation without chemotherapy and the treatment is likely to involve many breaks. Which again would prolong treatment time worsening the outcome further.

The point here, again, is what's best for the patient in terms of salvage. That issue has already been addressed.

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Reality is merely a persistent illusion

Re: treatment of inoperable T4 buccal mucosa cancer

Swarupa Mitra 13 May 2011 08:47

Thanks every one for the very informative discussion.
This patient was referred to our hospital after NACT, so i dont know the reasons behind.
At our hospital, I had insisted for treating him with radical intent with CCRT, although it was locally advanced.Yes. very rightly, i fail to understand the rationale behind NACT in oral and headneck cancers if they are inoperable atnthe outset.

But the treating team sent him for Chemotherapy again and now he has lung mets.

I brought this case for discussion as this type of cases are so very common, being sent after 4, 5 and even 6 NACTS.
Patients coming with large T4a or b tumours and not getting a chance for a radical intent treatment.

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Dr. Swarupa Mitra
Consultant Radiation Oncologist.
Artemis Hospital gurgaon
09812399708,9717041602

Re: treatment of inoperable T4 buccal mucosa cancer

Santam Chakraborty 13 May 2011 13:27

I hate to be blunt but NACT in head and neck cancer is beneficial for the oncologist and the pharma company… not for the patient

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Re: treatment of inoperable T4 buccal mucosa cancer

Chendil Viswanathan 13 May 2011 12:23

An Editorial published in JCO succinctly describes the perils associated with NACT in H&N Cancers

EDITORIAL
Induction Redux: Once More With Taxanes
David J. Adelstein
Journal of Clinical Oncology, Vol 23, No 34 (December 1), 2005: pp. 8556-8558.

EDITORIAL
Redefining the Role of Induction Chemotherapy in Head and Neck Cancer
David J. Adelstein
Journal of Clinical Oncology, Vol 26, No 19 (July 1), 2008: pp. 3117-3119

Review Article
Induction Chemotherapy: To Use or Not to Use? That Is the Question
David M. Brizel, Everett E. Vokes
Seminars in Radiation Oncology
Volume 19, Issue 1, Pages 1-68 (January 2009) ,Pages 11-16

Hope atleast after reading this article , our fellow colleagues will deter in following the said policy.

Last edited on 13 May 2011 12:55 by Chendil Viswanathan Show more

Re: treatment of inoperable T4 buccal mucosa cancer

Dr Prasad Dandekar 10 May 2011 07:43

Dear Dr. Swarupa,

Indeed this is a fairly common presentation in the OPD. I feel there is not much point in treating in-op BM is with radical radiotherapy alone. In this situation I would consider 2 options depending on the general health, disease status and affordibility of the patient.

1. If GC is not very good with very advanced disease and the patient is not very affordable, you could give palliative radiotherapy with 40 Gy in 16 fractions. This could possibly be followed by palliative chemo such as low dose Metho if responsive.

1. If patient is in good GC and is affordable, you could consider radical CT+RT+targeted therapy. The CT should not be the same drugs as NACT. Cetuximab or Biomab could be used in combination with CT + RT. The patient could be assesed 4 - 6 weeks post RT for operability. If the patient shows responce, but does not become operable, then we could continue Biomab / Cetuximab for a prolonged period.

Warm Regards,

Dr. Prasad Raj Dandekar
MD, DNB
Consultant Radiation Oncologist,
International Oncology Services Pvt Ltd,
Dr. L. H. Hiranandani Hospital,
Hill side Avenue, Hiranandani Gardens,
Powai, Mumbai, India - 400076.
Mobile: [phone]
Phone: [phone], Fax: [phone]
www.internationaloncology.com

Re: treatment of inoperable T4 buccal mucosa cancer

Santam Chakraborty 10 May 2011 13:41

Hi,
First of all a question: Why is this patient inoperable ? So far what I could gather is his stage is T4A. Is there something else thats making him inoperable. RMT involvement per se is not a contraindication to surgery but the reconstruction required is big.
To answer the question of the proper treatment now that NACT has been given I would only treat this patient with radical chemorad - the exact regimen depends on what has been given for NACT - I presume cisplatin was given so essentially very little choice. We use cetuximab in patients with more frail GC who are unable to tolerate CDDP - so this may be the right candidate. However I would need to know the age and NACT regimen though plus other details regarding the tumor like size, extent of invasion, patient's GC etc before a proper recommendation can be made.

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Re: treatment of inoperable T4 buccal mucosa cancer

Nikhilesh Patil 11 May 2011 02:35

I agree with both the speakers, either approaches are good, it really depends on the clinical impression of treating team.

Re: treatment of inoperable T4 buccal mucosa cancer

Swarupa Mitra 11 May 2011 07:33

This patient was not operated because according to the surgeon, the morbidity and the chances of residual disease were high and patient drew away. He was given cisplatin and taxane x3 cycles.age-42 yrs.
Cetuximab was offerd to him but cost factor came on the way.
What effect would radiation have in tumours involving skin and / or bone? There were heated discussions during our tumour board about the options of the treatment.

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Dr. Swarupa Mitra
Consultant Radiation Oncologist.
Artemis Hospital gurgaon
09812399708,9717041602

Re: treatment of inoperable T4 buccal mucosa cancer

Santam Chakraborty 11 May 2011 13:02

Hi Swarupa,
While it is unlikely that the patient is going to get a complete response it is also true the best response and the most durable response will come from CRT. Its difficult to say for this patient as he seems to have a poorly responsive tumor if it failed to respond to Cisplatin. 5FU based chemoradiation is an option but there will be higher risk of severe mucositis.
As far as the effect of radiation on tumor with bone invasion I always stand firmly by the argument that CRT is the modality with the best response. It seems that Chendil Vishwanathan who is also a member has had a thesis on this very topic. http://119.82.96.198:8080/jspui/handle/123456789/1893
The overall response rate was a healthy 50% - u will never get that with chemotherapy. In terms of international experience there is a recent publication in the red journal which I am sure are aware of dealing with outcome in patients treated for advanced oral cavity cancer with definitive CRT http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T7X-4YYV3B2-1&_user=2622728&_coverDate=11%2F15%2F2010&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_acct=C000057891&_version=1&_urlVersion=0&_userid=2622728&md5=9ac391e73c8802ebca57dfb7655e79ba&searchtype=a
Specifically for buccal mucosa the 3 year PFS was 51% .. I dont think we can expect this with any other treatment option. One thing that comes out of literature is the fact it is always better to approach these patients with salvage surgery as soon as possible as that enhances the LRC. There is a significant risk of osteoradionecrosis in view of bone involvement too. All these will probably feature in your consent.

This is a 42 year old patient. I am pretty certain he will be able to tolerate a radical course of Chemorad with proper nutritional support. it goes without saying that dental care prior to start of treatment is absolutely essential. I dont know how much this is applicable for your setting but I would have encouraged a second surgical opinion also -its not that he is not going to have residual disease after CRT or palliative CCT ..

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Last edited on 11 May 2011 13:07 by Santam Chakraborty Show more

Re: treatment of inoperable T4 buccal mucosa cancer

Chendil Viswanathan 11 May 2011 14:13

In my opinion it is best to formulate an Institutional protocol in the management of "ALL" cancers, because even though evidence based guidelines exists, the implementation of the same in-toto is difficult because of so many inter-dependent factors. ( I think everybody will agree with it). Cancer management is becoming increasingly comprehensive (previously the purview of only tertiary cancer hospitals and super-specialty hospitals) wherein all the related Departments (including Palliative care) involved in providing care and treatment to the patient are situated under one roof.

Since it is ultimately the skill of all people involved in the multi-disciplinary team which matters , I think Institutional protocols are the way forward in achieving the ultimate objective of curing a cancer patient taking into account the "Pros and Cons" of each individual cancer hospital. The same will help as a stepping stone in the formulation of newer treatment protocols in the future because each and every patient with a particular cancer will receive uniform treatment.

May be all the institutional protocols put together will become the onus for much needed and often quoted lack of data in our setting.

Re: treatment of inoperable T4 buccal mucosa cancer

radtuxabhishek 11 May 2011 14:55

It is very difficult to imagine that NACT would ever be able to affect the same degree of cure as compared to a radical course of CRT. A bone invasion would definitely require a surgery. It's difficult to presume from the outset that "any residual disease" would be left because by it's very nature the extensive surgery would also require Infratemporal Fossa clearance. That would also MINIMIZE the chance of leaving out any disease per se.

Cetuximab (or any other biological therapy) is unlikely to be of any benefit; primarily because the original Bonner trial did not include "standard fractionation" and oral cavity cancers were not part of the subset. Unless, there is a proper Phase III trial, extension to treat Buccal Mucosa seems to out of place.

There is an unfortunate trend to label patients with advanced HNSCC as "palliative"; perhaps we are too liberal with the terminology. We have treated patients with oro-cutaneous fistulas and exposed bone surfaces and seen very gratifying results; some cases with spontaneous closure. Of course, surgical salvage with excellent reconstruction has helped the matter nonetheless.

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Reality is merely a persistent illusion