Some of you may be aware of this case posted on isocentre by me in Nov 09.
This case I think is a good case to learn natural history of HNSCC for all of us
62 yr old man, good GC, Controlled DM
Had Ca Rt Buccal Mucosa 1999
Treated with W/E and Rt MND followed by EBRT 60Gy/30 # to rt face and neck.
Controlled for 10 yrs,
Developed I/L BM recurrence in June 09 treated with W/E and contralateral SOHD
pT2,No LN involved
Was advised RT by me.Didn't take
Recurred at suture line in Rt BM Jan 10
W/E Rt BM done Jan 10 and sent for RT
CT scan done (as MRI could not be done) to assess extent of primary and LN pathy
Showed Rt intraparotid LN enlargement although FNAC came negative.
Started on RT to Rt face and upeer neck @ 1.8 gy/# for 30-33 # but develpoed Rt parotid swelling post 4 #.
FNAC showed involvement by SCC. PET CT shows SUV 26 at parotid and 18 at tumour bed.
I am planning to restart Rt covering these areas and ipsilateral LN till level III as surgery is ruled out by surgeon.
What are your views?
Concurrent CT may compromise tolerance to RT and enhance late effects as this is reirradiation.
Sorry Nilesh, this chap has received 60 Gy to the Right face and neck in 1999.
Now you are treating the same Rt side (Re-irradiation)
Whats the intention of treatment ?
What total dose are you planning ? 1.8 Gy x 30# = 54 Gy ; 1.8 Gy x 33 # = 59.4 Gy
Wondered if these doses would be curative for gross disease out there.
concurrent Chemo would be of some use as of course you are exploiting the sensitsing potential to RT for greater damage.
We again come to the never ending debate ?
Surgery here is clearly the best option (thats of course if it can be done)
Would your surgeon be happy to consider any salvage later, i wonder ?
The only concern is the poor Mandible which is certainly heading its way to Osteoradionecrosis at those doses , this may be acceptable or not i dont know.
These scenarios are quite difficult as one part of your soul knows this is PALLIATIVE in nature making me adopt a minimalistic attitude,
where as the other side feels DO EVERYTHING possible and be a clever and smart oncologist, with a view to never saying "NO" to a pt. (These are the views when you have a pt right in front of you, when any of you put your boots in Nilesh s position)
I ve found a good easy to comprehend article which i d like to share.
Salient Points:
1. Current evidence indicates that in this group of patients reirradiation offers better control rates than palliative chemotherapy. The loco regional control rates of reirradiation without surgery is 20% at five years and 27% at two years. The overall survival rate with reirradiation ranges from 10% to 35% at two years and 0% to 14.6% at five years.
2. When surgery is not possible, reirradiation might be a feasible option for selected patients, particularly those with favourable prognostic factors such as second primaries, nasopharyngeal or laryngeal tumours or delayed recurrences.
3. Long disease free interval
In the RTOG 96-10 trial it was found that patients who received their primary radiation three years or more before the repeat radiation had a one-year survival rate of 48% as compared with 35% for patients treated within three years ( P = 0.017). The interval between prior radiation and re-irradiation was however, not a significant prognostic indicator of survival in RTOG 96-11.
3. Radiation dose intensity
Radiation portals must be tight to avoid excessive irradiation of normal tissues
Adequate radiotherapy doses are needed for optimal outcomes in radical reirradiation. High doses of reirradiation are necessary in the radical treatment of recurrent tumor, because of the origin of recurrence from radiation resistant clonogens. Various studies have shown higher control rates with higher doses of radiation.
Haraf et al reported a two year survival of 35% in patients who received over 58 Gy as compared to 8% in those who received less than 58 Gy. Langlois et al showed that local control was achieved in 55% of patients who received a dose greater than 60 Gy as compared to 8% for doses less than 60 Gy.
4. The most serious reported toxicity is carotid rupture, which occurs in 1-5% of patients, in the setting of re-irradiation.
De Crevoisier reported osteoradionecrosis in 16% and cervical fibrosis in 40%.Data from the University of Chicago show that only 25% of patients were able to swallow solids without dependence on enteral supplementation.
5. The frequency of significant hematologic toxicity varies and depends on the chemotherapy regimen used. The combination of hydroxyurea and 5 Fluorouracil (FU) has been found to have only mild to moderate myelosuppressive effects with fewer than 10% of patients developing grade 3 or 4 neutropenia, as compared to regimens such as docetaxel/cisplatin and paclitaxel/cisplatin where grade 3 or worse neutropenia occurs in approximately one third of patients.
Their basis conclusion from review of literature is the reirradiation dose should be optimum, ranging from 60 to 70 Gy. Patients must be fully informed of the potential life-threatening toxicities and the impact on quality of life.
I am interested in the results of the first randomized trial comparing re-irradiation and concurrent chemotherapy versus chemotherapy alone for inoperable, previously irradiated, locally recurrent or second primary squamous cell head and neck cancer which completed accrual of pts last year. [ RTOG 0421 ]
http://www.rtog.org/members/protocols/0421/0421.pdf
Is there any evidence to the use of Gefitinib. Are any trials being done on RT with gefitinib in re-irradiation or palliative cases.
Anecdotal, empiric experience- a lady had oropharyngeal recurrence post RT and has been doing well for last 14 months on gefitinib.
Rohit nice to see you in action. Those who know, can feel your personality in your writing also.
Thanks Harsha for your note. I promise total entertain whenever i m around —- as i speak about evidence in the clinic and nothing but evidence on isocentre.
With regards to use of EGFR with RT, the final word has yet to written. I did a presentation on this a couple of years back.
With regards to use in chemonaive new pts with locally advanced H & N, there is quite a lot of work going on in PH II and Ph III Trials. Just a brief overview for your interest.
https://docs.google.com/Doc?docid=0Aev7QBrXiE51ZGZtYnNxcGZfMTRncmdwM3RkbQ&hl=en
Few of these above trials have now closed and would have reported its interim results.
But i must add and point out that the interest of the international community is less towards use in concurrent setting, but their eyes are on Maintenance treatment after completion of concurrent chemoRT. Thats where the future is being driven for these agents, with the exception of the Bonner study of course, when you CANT use cisplatin based CTRT in a few pts, hence use cetuximab in concurrent setting.
But regards to Re-irradiation, there are hypothetical arguments for its use as from a few very good review articles.
But you would be more interested in the clinical side, where the data is still scarce.
There are a few instances where pts who were treated with re-irradiation along with EGFR inhibitors, there has been complete necrosis of the skin in the area of re-irradiation, raising concerns regarding safety of this approach.
www.nccn.org/JNCCN/PDF/2009_Derm_Tox_TF.pdf
Hence its use should be regarded as experimental and not used outside the setting of a clinical trial.
I have come across only one reported Ph 1 Trial of re-irradiation concomitant with erlotinib followed by maintenance erlotinib.
http://www.ncbi.nlm.nih.gov/pubmed/20231078?dopt=AbstractPlus
Another bold ongoing trial at the Mount Sinai School of Medicine is
Erlotinib + Celecoxib and Reirradiation for Recurrent Head and Neck Cancer
http://clinicaltrials.gov/ct2/show/NCT00970502
In this phase I/II study, patients will be treated with daily erlotinib 150 mg and twice-daily celecoxib 200 to 600 mg for 14 days. Re-irradiation with IMRT will start on day 15 and will continue for 5.5 to 6.5 weeks along with erlotinib and celecoxib. After completion of radiation, patients will be given the option of continuing on erlotinib for 2 years or until unacceptable toxicity or disease progression .
Coming back to Nilesh and his basic question about chemotherapy along with RT. (concentrating on what Nilesh wants to know). Have a look at this article
http://www.ncbi.nlm.nih.gov/pubmed/16213104?dopt=Abstract
Various chemotherapy regimes have been used in this article from University of Chicago Pritzker School of Medicine.
I m amazed by the median lifetime radiation dose being 131 Gy, Wow
and just wondered about Nilesh , 60 Gy given to Rt F + N in 1999 ; another 71 Gy to go -—->2010
I would nt necessarily recommend that dose but err on the side of caution again on the same principle
primum non nocere (first do no harm ) Vs Beneficence (helping the pt)
The doses suggested by Nilesh probably seem reasonable, around 60 Gy but i would treat it with conventional fractionation and not at 1.8Gy/# or else calculate BED and increase your fraction numbers
and if you are too keen and cautious about Late tissue damage, perhaps altered fractionation ( oops i ve opened pandoras box here)
But adding chemotherapy in this scenario seems logical as there is some Level 3 evidence to back that decision.
Hi Nilesh,
I guess, there is not much to speak after the detailed discussion done by Rohit. Since, he did mention about altered fractionation, just wanted to add a comment. Here at PMH, for all re-irradiations, the fractionation used is 1.1Gy/# BID 6 Hrs apart. We try and reach a dose nearing 60 Gy. This becomes adequate especially in scenarios where the recurrent gross disease has been surgically debulked. Pts. tolerate it very well acutely and biologically it is expected to have much better late tissue effect; something that you might want to use in your patient. We have been using this fractionation along with concomitant weekly cisplatin to provide additional radiosensitisation. Though one might debate that this can also radiosensitise late tissues…!!
In your case, with a 10 Yr gap, one could dare to reach about 66 Gy to a limited volume, obviously discussing the risks and benefits with patient. As pointed out in discussion above, very limited radiation volumes is the key here…. just to gross disease primarily. I would presume that BID fractionation is logistically feasible in a private health care scenario back home.
Just a quick question.. why was surgery ruled out.. Surgeon's preference or was it a real issue? I believe, if recurrence is still limited to oral cavity, even with intra parotid nodes, it should still be resectable. Will your surgeon be willing to operate if this patient does develop a complication.. like ORN or vessel blowout or just necrosis? On a lighter note, I remember one of the comments Bhushan used to say about some surgeon….The only contraindication for surgery in his mind was disease infiltrating the OT table or metastases to patient's relative.