PD Adenoca of nasal cavity

Summary:

Adjuvant RT for a rare histology

PD Adenoca of nasal cavity

Indranil Mallick 02 Feb 2010 04:04

Patient demographics

65 yr old lady

History

Long standing history of R nasal blockade, and occasional epistaxis x 6 months

Clinical Features

Fleshy mass in R nasal cavity. No mucosal changes on L side. No palpable neck nodes.

Tests

Pre-op MRI shows large mass filling R nasal cavity encroaching in R maxillary sinus and superiorly extending upto the base of skull. No radiological evidence of intracranial extension. No radiological lymphadenopathy.

Chest CT - clear

Treatment details

Craniofacial resction with complete excision of tumor (but not en bloc).

Path shows a poorly differentiated adenoca with neuroendocrine features (synaptophysin +ve) - this is not an intestinal type adenoca nor a small cell neuroendocrine lesion. Glandular structure with some squamous differentiation. Biopsy from dura positive fore tumor involvement, otherwise margins clear.

Final Diagnostic summary

PD adenoca of R nasal cavity with neuroendocrine differentiation, post craniofacial resection, presumably R0 but positive dural involvement.

Issue(s) for discussion

Referred for adjuvant RT

• Dose?
• Volumes - would you treat nodes?
• Chemo?

Re: PD Adenoca of nasal cavity

Santam Chakraborty 02 Feb 2010 13:56

First question will adjuvant RT help .. evidence is slim in this regard actually but most people will treat with RT
Coming the questions:

1. Dose: Piet Dirix, Sandra Nuyts, Yasmyne Geussens, Mark Jorissen, Vincent Vander Poorten, Eric Fossion, Robert Hermans, Walter Van den Bogaert, Malignancies of the Nasal Cavity and Paranasal Sinuses: Long-Term Outcome With Conventional or Three-Dimensional Conformal Radiotherapy, IJROBP, Volume 69, Issue 4, 15 November 2007, Pages 1042-1050, Shows giving a dose of 60 -66 Gy in adjuvant setting is associated with a poor overall control (65% LC) so increasing the dose with IMRT to 70 - 72 Gy should be the goal.
2. Volumes : Treat generously . I would include the nasal cavity, ethmoid and sphenoid sinues, nasopharynx, maxillary sinus on right side, pterygo maxillary fissure, pterygopalatine fossa, ipsilateral infratemporal fossa, inferior orbital fissure, cribriform plate, and adjacent dura for a distance of about 2 cm around site of intracranial involvement (this one can be best contoured on coronal slices). This is the HRCTV which should receive a minimum dose of 66 Gy (preferably escalated to 70 Gy). Why? Angel I. Blanco, K. S. Clifford Chao, Gokhan Ozyigit, Mustafa Adli, Wade L. Thorstad, Joseph R. Simpson, Gershon J. Spector, Bruce Haughey, Carlos A. Perez, Carcinoma of paranasal sinuses: long-term outcomes with radiotherapy, International Journal of Radiation Oncology*Biology*Physics, Volume 59, Issue 1, 1 May 2004, Pages 51-58 - shows a high incidence of failures at the penumbra and low dose areas. Nodes - yes in advanced malignancy with dural involvement.
3. Chemo: Yes concurrent CDDP should be tried if tolerance permits. Going by the rationale of treating poorly differentiated carcinomas in nasophayrnx.

---

Re: PD Adenoca of nasal cavity

Indranil Mallick 02 Feb 2010 22:23

Hi Santam
Thanks for the response. My initial response was the same as yours, although I now have a different outlook on this after thinking about a little longer.:
Firstly - this is an extremely uncommon histology - a pd adenoca with neuroendocrine features is extremely rare (the usual adenoca in the nasal cavity are different) and among neuroendocrine carcinomas - this is not the usual small cell or the intestinal type. Therefore there is no 'good' evidence on this.
Now let's looks at the 3 issues discussed:
1. Dose - the paper that you have quoted shows that 5 year local control is relatively poor, but then these are traditionally difficult to cure tumors. The results for adenoca were much better than that for SCC and in their limited analysis there was no suggestion that 60Gy or less in the adjuvant setting resulted in any more failures than 66Gy. In fact I don't have any reason to try to push dose to beyong 66Gy here in the adjuvant setting and cause extra morbidity to optic structures, brain, hormonal axis etc.
2. Volumes: The idea is to take the preop volume and make sure that there are adequate margins at the skull base where the dura was positive. BUt why should I treat all your suggested areas to 66Gy. Why should I treat microscopic regions to more than microscopic doses? The key is to evalute pre-op imaging accurately. If you noticed the preCT era results are worse than post-Ct era results in the paper from Perez. As far as nodes are concerned there is in fact no evidence for treating nodes electively in these cancers. In the first paper that you have quoted only 5/127 patients had their neck addressed primarily, in the 122 whose necks were not treated, only 6 failed and all but one was salvaged I think. Of the 6 only 1 was adenoca. If I had to which nodes would you suggest I treat and why?
3. Chemo - why should I give concurrent cisplatin in a PD adenoca? Agian this is not a small cell type ca either. In fact I am unaware of any good evidence for chemo in PNS and nasal cavity non SCC patients.

There has been only one case of a nasal cavity PD adenoca in the practice of the treating rad onc. This patient was diagnosed some 15 years back. Was treated with surgery + RT. Failed locally 5 years later and has been living comfortably with the base of skull recurrence for the last 10 years. Go figure!

Re: PD Adenoca of nasal cavity

Nikhilesh Patil 02 Feb 2010 22:39

Very interesting case. Treating PNS tumors has always been a challenge. I tend to agree with both of you in this case. I would try to give maximum dose and no Chemo as I dont have any strong data to support, also tolerance can be an issue.This reminds me you can send this case for ESO Master Class, deadline sometime in May 2010.

Re: PD Adenoca of nasal cavity

Ashwini Budrukkar 04 Feb 2010 04:27

Its difficult to comment on possible doses without seeing images. Theoritically though doses of >60Gy are recommended they are many a times not feasible due to proximity to critical structures and doese to critical structures.

Indranil, can we put images on to this??

Ashwini

Re: PD Adenoca of nasal cavity

Indranil Mallick 04 Feb 2010 05:05

Technically possible to put images on this website, but I have to do it from work tomorrow.

Re: PD Adenoca of nasal cavity

Nikhilesh Patil 04 Feb 2010 05:24

Dont forget to remove patient identifying factors from the images. In fusionefilm you just have to click big letter "A" to do that and export the image as jpeg.
Nikhilesh

Re: PD Adenoca of nasal cavity

kundan_25 08 Feb 2010 01:55

Rare entity and it is always difficult to have evidence every possible entity. Regarding dose I agree with most of you. Area with preop tumor 66 Gy. Concurrent Chemo I am not sure again going only by evidence in this case is not worth but logically adenocarcinoma (though not usual) we dont use CCRT always in head neck region.

Re: PD Adenoca of nasal cavity

AAM 08 Feb 2010 09:02

Referred for adjuvant RT

There is little evidence for action in this disease. In 1997 I had a patient with neuroendocrine carcinoma of the ethmoids/nasal cavity (isocentre of disease difficult to know). The data was worse than sparse. I contacted all departments in Australia and NZ to see if some cases could be cobbled together for a "rare cancer" report, and I couldn't find another department with a patient! Interestingly I have seen 2 adenocas of the nasal cavity in the last 12-18 months (both wood workers). One failed distantly, the other is starting soon, but neither had neuroendocrine features.

• Dose?
  • the reason for treatment is local control. The surgery was not adequate AND there is the dural invasion. As such the dose to use is the dose that respects tolerance of nearby local structures.
    • A priori I would be aiming for a dose of 70Gy to the 'at risk' area, as that is a tolerable dose to the non-critical structures.
    • I would CT plan with MRI fusion of post-op appearance.
      • My target volume (CTV) would include the entire cavity of resection. However I would pay particular attention to the surgery and ask the surgeon what exactly was taken, and then attempt to correlate this with the histopathological findings (I would risk adapt my margins into normal mucosal tissue).
        • I would expand the CTV margin by my set up accuracy to produce PTV7000 - I use 3mm as our department uses a daily IGRT approach with a 3mm tolerance for movement.
      • I would also contour OARs [2]
        • All of these structures (except BRAIN) would be expanded by the expected movement (3mm) to create planning restriction volumes [3]
        • BRAIN would be expanded by the movement quantity (3mm) and then clipped 7mm back from the PTV7000. [4]
    • My prescription would be: 70Gy in 35Fx using IMRT at the calculation point [1], with constraints in the following order:
      • OAR_PRVs (but not BRAIN) are to be covered by the 4400cGy, but not exceed the 4500cGy isodose
      • BRAIN_PRV is not to exceed 6000cGy
      • 98% of PTV7000 is to be covered by 95% of 7000cGy [5]
• Volumes - would you treat nodes?
  • I would not treat nodes at any level. I don't know which nodes the dura drain to anyway. Can anyone inform me?
• Chemo?
  • I would not ask for concurrent chemotherapy, however I would not argue with a decision to treat during or after the radiotherapy. I would look closely at the isodoses achieved on the plan keeping in mind the possibility of dropping my dose to 6600cGy with concurrent chemo. I would expect that the chemotherapy would be the carbo/cisplatin-etoposide doublet, but would not argue with concurrent weekly cisplatin.

Bibliography

1. I do not prescribe to the isocentre as simulation staff place the isocentre on a very identifiable bony landmark in the H&N to aid with accurate and rapid isocentre placement

2. specifically GLOBE_R/L, LENS_R/L, OPTIC_N_R/L, CHIASM, BRAINSTEM, BRAIN, LACRIMAL_R/L

3. specifically GLOBE_R/L_PRV3, LENS_R/L_PRV3, OPTIC_N_R/L_PRV3, CHIASM_PRV3, BRAINSTEM_PRV3, LACRIMAL_R/L_PRV3

4. the way I do this is to expand the PTV7000 by 7mm to a fictitious volume called PTV_PRV and the expand the BRAIN contour while avoiding the interior of the PTV_PRV

5. this constraint comes last because, in all probability, it cannot be achieved, and it is important to avoid critical organ damage in a setting where there is no well documented imperative to treat.

Re: PD Adenoca of nasal cavity

Santam Chakraborty 08 Feb 2010 13:17

This is turning out to be quite an interesting discussion. I would like to clarify a couple of points:

1. My idea in escalating the dose to 66 Gy to the whole CTV is based on the premise that adenocarcinoma is likely to be more radioresistant. At the same time its true that no real evidence can say that a dose more than 54 Gy will be helpful in controlling microscopic disease. My premise for the 66 Gy to this volume is that we have been regularly delivering 60 Gy or higher doses to these areas with conventional technique and in this case if we are to use the full benefit of IMRT then dose escalation should be tried. That said I have treated quite a few patients with doses in the range of 66 -70 Gy with little neurological complications.
2. Why the nodes? This one is a very controversial aspect of the treatment plan. My premise was the fact that involvement of the base of the skull may mean involvement of the retropharyngeal space (as Ashwini mam said having images would have helped). This and the fact the histology is poorly differentiated would prompt me to treat the ipsilateral level II/III nodes to a dose of 50 -54 Gy. Well to tell the truth the idea for this comes from a patient with a poorly differentiated sinonasal tumor that I had treated in 2006 who had developed a nodal progression during RT. In my opinion one failure is too many and giving that dose with IMRT is unlikely to lead to severe morbidity. At the same time I acknowledge that in event of the rare nodal failure a neck dissection can be opted for.
3. CDDP is an active agent in the management of other adenocarcinomas and has good and proven tolerance with RT. That said CDDP/ Eto doublet I am not sure how the tolerance will be. What chemo you feel you should give if you had to give?
4. When i said escalate dose to 70 Gy I meant a SIB technique contouring the residual abnormality (and probably the preop volume) to the volume receiving 70 Gy and rest of the CTV to 66 Gy.

---

Re: PD Adenoca of nasal cavity

Santam Chakraborty 08 Feb 2010 13:23

An interesting article on dural and CSF lymphatic connection
http://www.cerebrospinalfluidresearch.com/content/2/1/6

At the same time I doubt the tumor involving the dura will go through the nodes :-)

---