62/M
5*4 cm Rt BM lesion involving lower alveolar mucosa. No palpacble LN
Biopsy: Verrucous Ca
CT not done yet
Unfit for surgery due to cardiac morbidity.
What are the treament options?
Should we offer him radical RT as there is no other treatment option?

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.

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.

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.

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..

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.

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.

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.

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 ..

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: +91 9820040454
Phone: +91 22 25763300, Fax: +91 22 25763311
www.internationaloncology.com