Elderly male with carcinoma epiglotis

Summary:

76 year male (belongs to Doctors family). Mod diff sq cell Ca Limited to epiglotis. Clinically neck negative but radiologically level II 2 lymphnodes with central necrosis (Max Dimension 1 cm). Family wants least morbid treatment. Kindly opine on the line of management. If RT then volumes to be included and what about concurrent chemoradiotherapy. Some one has suggested them surgery but I am not in favour of surgery.

Elderly male with carcinoma epiglotis

kundan_25 15 Feb 2010 11:14

76 year male (belongs to Doctors family).
Mod diff sq cell Ca
Limited to epiglotis. Clinically neck negative but radiologically level II 2 lymphnodes with central necrosis (Max Dimension 1 cm). Family wants least morbid treatment. Kindly opine on the line of management. If RT then volumes to be included and what about concurrent chemoradiotherapy.
Some one has suggested them surgery but I am not in favour of surgery.

Kindly give your opinion regarding the management. They are personally known to me and the family is od doctors.

Re: Elderly male with carcinoma epiglotis

Indranil Mallick 15 Feb 2010 16:33

Hi Kundan
I would explain to the patients family that I will aim for cure but be aware of his clinical circumstances and modify the treatment aprroach as we go along. I would treat with IMRT if they can afford it. I would not push chemo.
Dose: I would treat aim for a dose of 70Gy/35Fr (or whatever you use as a radical dose). If the patient is a relatively fit 76 year old I would consider acceleartion with a DAHANCA approach. if not just the usual fractionation schedule. Sometimes shorter course treatments work well e.g. 60/25 or 50/20 in this setting. Treatment breaks or early discontinuation if clinically indicated.
Volumes for this gentleman: GTV + margin to radical dose. Further margin of 5-7 mm for microscopic dose. involved level 2 to radical dose. Other volumes (bilateral levels 2-4) to microscopic dose. I would avoid level 5 bilateraly and high level 2 (above the junction of digastric with carotids) on the contralateral side. I would not go very inferiorly with the level 4 contours (i.e. stop at the post cervical vessels). I would try my best to reduce doses to oral cavity.
Supportive care: Ensure adequate pain control and reinforce dietary advice.
Best of luck.

Re: Elderly male with carcinoma epiglotis

Nikhilesh Patil 15 Feb 2010 17:18

Hi Kundan, I agree with Indranil's suggestion. Please do not offer surgery. Radical radiation alone is an reasonable option and keep surgery as a fall back option.

Re: Elderly male with carcinoma epiglotis

kundan_25 16 Feb 2010 01:51

Thanks
I do agree with you they and have no financial constraint. I have suggested them IMRT with simultaneous boost.

As far as RT volumes are considered our standard protocol is

We only use two volumes

CTV1(For gross disease) = GTV+1.5cm Margin+ PTV(0.5mm) = 70Gy/35#
CTV2(For elective nodal volumes) = if neck positive on that side comprehensive neck irradaiton (all levels 1b to level 2(upto base skull) Level 3 Level 4 level 5) = 56Gy/35#.
I know I will have to modify these volumes for this patient. I am concern about concurrent cisplatin. As far as MACNC update analysis says that there is no benifit of chemo above the age of 61 years. I was thinking of trying DHANCA 6 fractions a week approach with no chemotherapy.

Re: Elderly male with carcinoma epiglotis

vijaypgi 16 Feb 2010 17:09

I want to know a few more details about this patient.Whats the KPS,does he have any Chronic comorbid conditions. How can we think that a patient who cannot tolerate an Partial larngectomy + neck dissection (if its considered too morbid ) would actually tolerate an Radical course of Radiation. Further giving an altered fractionation in this age group, i have my own doubts . If i recollect correctly age above 70 in Bourhis et al metaanalysis had an hazard ratio of more than one,so its quite harmful.Even in Overgaard analysis age group above 65 had an hazard ratio of more than one.So for me for this patient altered fractionation is out. No Question of Chemoradiation here as again the hazard ratio is more than one for an age group more than 70.
I would contour the neck according to the guidelines provided by Greggoire et al, where Ipsilateral all nodes from level 1b-to 5 would be contoured, however i would stop my level 4 contour about 2 cm above the suprasternal notch. Contalateral i would contour only 2-4, here i wont go uptill the base of skull for level 2. Only Ipsilateral level 2 which harbors a likely positive node would be included in high risk CTV(HRCTV) . If this node is at the junction of any adjacent level then that level will be included in HR CTV. I think it would be better to contour GTV and adacent space (pre epi,vallecula,suprahyoid larynx) then just giving an margin around the GTV.
Would this patient be an candidate for an intestitial implant + neck dissection in the same sitting?

Re: Elderly male with carcinoma epiglotis

Indranil Mallick 17 Feb 2010 05:31

Hi Vijay
Thanks for joining the discussion, and you have brought out some great points here.
a) the issue on surgical fitness is relevant and comorbidities have to be taken into account. But the issue may be beyond immediate surgical fitness or acute morbidity. Surgical removal of the epiglottis may leave an elderly gentleman with a huge chance of aspiration. And if there is any extension into the BOT, this may be more than a partial laryngectomy. In this setting, radical radiation therapy will still be my recommended approach.
b) It's great that you pointed out the effect of age on outcomes after chemo or altered fractionation, and you are right that the benefits of either approach diminish with age. This has to be kept in mind when making the final decision on treatment. I went back and checked the data on age and altered #. I note that although the meta-analysis reports a HR > 1 for age >71, in the DAHANCA 6&7 the HR was 0.78 (0.56 to 1.09) and not far from significant improvement (http://www.ncbi.nlm.nih.gov/pubmed/14511925). Interestingly the figure has an error in this paper in this section that is corrected in an erratum later. On this basis - I would not completely discount DAHANCA 6/week as an approach if this gentleman is relatively fit with a good performance status. In fact I would hate to generalize on the age issue because it is severely dependent on comorbidities (a factor not commonly included separately in multivariate analyses).
c) In terms of volume I have reservations about including level 1b and 5 in the ipsilateral neck for a small volume single node in level 2. If you look at Gregoire's compilation of studies from surgical literature (http://www.ncbi.nlm.nih.gov/pubmed/10927132) the incidence of positive LN from 'therapeutic' neck dissections in supraglottic larynx (table 7) in level 1 and 5 are 6% and 5% respectively. Also look at the classic Lindberg diagrams in Perez on nodal involvement patterns. In a gentleman in whom morbidity is a big issue I would gladly leave them out (to individualize). I would of course also base my decision on the location of the level 2 node. In particular - avoiding 1B will allow me to reduce oral mucositis. If you look in standard textbooks - conventional portals for supraglottic larynx cancers do not usually include 1b - although individual institutional protocols may vary. I completely agree that for the primary anatomic regions are a better idea in comparison to geometric margins.

Re: Elderly male with carcinoma epiglotis

Nikhilesh Patil 17 Feb 2010 06:00

Dear Vijay, your participation is greatly appreciated. I agree with Indranil, surgery will be too morbid, simple radical radiation will give you good results, studies already quoted. If ever in doubt think as if the patient is your own relative and your decision will never go wrong. This is what I do when I see a tricky case.

Re: Elderly male with carcinoma epiglotis

Santam Chakraborty 17 Feb 2010 07:53

Hate to be a heretic but isn't a transoral laser excision the least morbid procedure in this situation.

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Re: Elderly male with carcinoma epiglotis

AAM 17 Feb 2010 10:44

There are a couple of things that I would consider:

Firstly, the family - they need to be talked to! Firstly who is the doctor? The family members are helpful as purveyors of information for Dad but they aren't doctors, they are CHILDREN of the patient. You might consider handing the patient over to some-one else and acting as an overseer to verify that all is done properly.

Secondly, the issue is - do they want Dad cured or not? The side effects are affected by your volumes, but also by his radiosensitivity and his underlying condition. No RT or surgical cure came by backing off treatment. The least morbid treatment is the "one-stop shop". Laser resection will be OK once but with recurrence will enhance aspiration with second attempt or salvage RT, and won't address the neck LNs. RT reigns supreme for him.

Thirdly, my personal impression is that his cure potential is the same as a younger patient, his toxicity potential is equal, but his ability to cope with and rebound from the toxicity is much poorer.

Fourthly, I would consider an concurrent adjunct therapy like cetuximab, but not chemo.

Fifthly, the side effects will be related to the fineness of the voluming and the CTV>PTV margin which will relate to your IGRT protocol.

Sixthly, if I was to be trotting out the piece de resistance treatment, I would ask for an IGRT approach with a dead-on set up margin. I would get a PET to help delineate extent in mucosa (a rough guide), and then contour the mucosa and build a mucosa_PRV structure to limit dose in the posterior pharyngeal wall. (I do this by autocontouring the air-tissue interface, expanding to a 2mm larger structure and then subtracting the first from the second to leave an annulus which I call "MUCOSA". I expand my PTV6000 by 7mm to form a theoretical construct called the PTV_PRV and then take the MUCOSA, expand by the setup margin (1-2mm) and exclude from inside the PTV_PRV, and I am then left with the MUCOSA_PRV which is more than 7mm from the PTV6000. This is the mucosa that can be conserved and so should get a high priority in the IMRT constraints.) This method would result in minimised mucosal doses.

The neck volumes are largely irrelevant w.r.t the toxicity.

Re: Elderly male with carcinoma epiglotis

Ashwini Budrukkar 17 Feb 2010 17:26

I agree completely with Indranil

Indranil..i am ur fan……..

Re: Elderly male with carcinoma epiglotis

Harsha Dod 18 Feb 2010 07:16

This has definitely become much better. Hats off to you all.
In carcinoma epiglottis, even with radiation i have seen very high aspiration rates. I think basically it has got to do with the structure and function of epiglottis. how to prevent or circumvent is a challenge?
In fact three days back , i had a similar patient elderly male with Carcinoma Epiglottis T2 N0 M0. Offered IMRT,
but explained all the toxicity, need for PEG/ryles tube etc. Last heard patient is window shopping and considering ayurvedic!!

Re: Elderly male with carcinoma epiglotis

vijaypgi 18 Feb 2010 18:36

There are a couple of things , i like to clarify
1) Gregoire's compilation of studies from surgical literature (http://www.ncbi.nlm.nih.gov/pubmed/10927132) the incidence of positive LN from 'therapeutic' neck dissections in supraglottic larynx (table 7) in level 1 and 5 are 6% and 5% respectively. --- Ok agreed BUT if u look at the same paper in table 2 ,where the clinical distribution of metastatic lymph nodes is given the incidence of ipsilateral level 5 lymph nodes is 15% in supraglottic larynx.Also around 45% of these patients were No.Considering this figure i would still like to treat ipsilateral level 5 in node positive N2b(level II 2 lymphnodes with central necrosis) Further the number of patients which were complied for generation of this data is much higher than the number of patients reported by candela et al on the basis of which the data in table 7 is based. Also i like to highlight that in the analysis by Candela et al its mention that though involvement of level 5 is rare it seen in conjuction when lymph nodes are positive in level 2-4 and selective neck treatment is only recommended for N0-1 neck. I agree that involvement of level 1b is a bit rare but i would like to know the exact location of the lymph node in level2 before excluding it.
2) Surgery or Radiation , here i am unaware of the T stage of this tumor, so i would discuss it with each T stage in consideration
Limited T stage (T1-2)- frankly there are no randomized studies in which radiation therapy was compared with conservation surgery with respect to local control or survival for patients with limited-stage laryngeal cancer. Similarly, there are no randomized controlled data on comparison of functional outcomes, specifically the quality of voice and swallowing ability, after surgery or radiation therapy for patients with this stage of disease.However American Society of Clinical Oncology Clinical Practice Guideline for the Use of Larynx-Preservation Strategies in the Treatment of Laryngeal Cancer has mention
Favourable supraglottic cancer ( T1/2)- Open organ-preservation surgery associated with highest local control rates; however, requires temporary tracheostomy and may lead to increased risk of aspiration after therapy; local control rates after radiation therapy are also high, and functional outcomes may be better.
But if toxicity or morbidity is a concern Endoscopic resection can be tried. A study Csanády Jr has tackled such pts with laser excision and neck dissection in the same sitting;Comparable controls have been obtained . 73% patients after laser surgery showed no recurrence after a single laser-excision.Similar results are also published by HANS EDMUND ECKEL et al. So why not this option if morbidity is a concern? 76 being the age wont an adequate local control with minimal morbidity would be provided.
Unfavourable- Open organ-preservation surgery is more likely to yield higher local control rates than radiation therapy; for patients with T2 N+ disease, evidence from randomized trials supports concurrent chemoradiation therapy as an organ-preservation option. BUT in this patient this option is not there.
MERE invasion of BOT doesnt make organ preservation surgery impossible , its containdicated if impaired tongue base mobility or Cancer within 1 cm of circumvallate papilla (http://www.ncbi.nlm.nih.gov/pubmed/19442314)
T3-T4 - patients with tumor penetration through cartilage into soft tissues are considered poor candidates for a larynx-preservation approach. Primary surgery, usually total laryngectomy, is commonly recommended in this setting.
Concurrent chemoradiation might help but that option is not viable in this situation.(especially in T3) I agree that DAHANCA fractionation can be used.But the ability of 76 year to cope with the toxicity would be questionable.

Last edited on 18 Feb 2010 18:48 by vijaypgi Show more

Re: Elderly male with carcinoma epiglotis

Indranil Mallick 19 Feb 2010 03:48

Hi Vijay
a) Again, excellent observation with table 2. Frankly, I am not sure why table 2 and 7 are so different. In fact Chao's compilation (http://www.ncbi.nlm.nih.gov/pubmed/12128118) agrees well with table 2 here (probably because the sources are similar) and quotes 16% incidence. His recommendations however surprisingly leave out level 5 in ipsilat/unilat N+ disease (don't know why). I concede that level 5 is not so clear cut. I guess that only the treating physician can decide if the level 5 is truly at risk based on the position of the level 2 nodes. As Andrew points out - unilateral level 5 treatment is also not really likely to majorly increase toxicity. As far as level 1b is concerned - I would certainly leave that out.
b) here I can't agree with you - if you don't mind a personal comment from me - I think you are being way too theoretical here. You are quoting results from the best laser /endoscopic resection studies from the best people in the business. I haven't yet met any surgeon in India or Canada in Tata /PMH who actually even offer this to epiglottic cancers along with a neck dissection. If the surgeon is not very experienced you are at high risk of facing a positive margin and then you are in big trouble as a rad onc.

In general I think we are overdiscussing these issues theoretically (and I am a prime culprit here). I think Kundan has enough ammo to go by - now he has to make up his mind and go for it - and let us know what he did.

Re: Elderly male with carcinoma epiglotis

AAM 19 Feb 2010 04:35

yes,

a. anterior 2 node would prompt ipsilateral 1b coverage, but posterior 2 node not in front of SMG; contralateral N0 neck would be 2/3/4 alone. Personally I wouldn't include L5 UNLESS I could see nodes there
b. wholeheartedly concur - laser resection is boutique at present and you would need an excellent operator. Those reports are from the leaders AFTER their learning curves. We touched on this in our contouring discussion also - the ability to translate treatment from the avant garde to the followers when a lot is based on feel and experience.

Re: Elderly male with carcinoma epiglotis

kundan_25 19 Feb 2010 08:18

Thanks everyone Nikhilesh, Vijay, AAM

Nice discussion.
No doubt we have to irradiate. He is planned for IMRT five fractions a week treatment. I have planned for 70 Gy in 35 fractions and he has recieved first fraction today. Level II nodes are anterior no distortion very small (nearing 1 cm) although there is a central necrosis. If we look at the performance status he is KPS 70 but there are no comorbid conditions. Overall look is frail. I have included bilateral level II(not upto base skull, Level III and LevelIV).
As far as my personal experience go I have treated two such patients both base tongue T2NOMO age 78 and 74 (with KPS 80) with RT alone IMRT(Level II, III, IV). One was ryles tube dependent for 5 months but now post 9 month he is disease free with Grade II xerostomia with normal swallowing function. Other patient Ryles tube dependent 3 month and 6 month down the line disease free with normal swallowing function and good saliva.
So I am convinced with majority of you that one has to go for RT with radical intent. Inclusion of levels is controversial especially Level IB.
Once again thanks for your inputs and nice crisp compilation of literature.