My case is a OP case. It is a T2 N1 SCC of the anterior tonsillar pillar. This is the palate and you see the right side of the uvula here. It is an exophytic lesion. The center of it is in the anterior tonsillar pillar. It involves the lateral 1/3 of the soft palate. At CT we have 1 enlarged LN at the level 2a, JD node, at the level of hyoid bone. This tumor was stained positive for HPV. The patient is a non smoker, that is less than 10 pack year.

The question is which is the primary treatment, primary surgery or RT with or without ChT.

Tha majority of the audience voted for primary RT. I am surprised as the indications of the american surgical society are for a surgical approach.

Our standard at the university of florida is primary RT. We do not see a marginal advantage of adding ChT in this T1 – T2 low volume N0 patient so we treat this people with RT alone. We are now engaged in a deintensification protocol but the treatmentis 70 Gy at high risk CTV. We use the RTOG protocol with 56 Gy at 1.6 Gy per F to the elective regions. In this case we elected to treat the contralateral level 2 – 4 nodes. For HPV cancer the range of RT dose is 66 – 70 Gy. We are engaged in deintensification protocol with 60 Gy plus weekly P.

The patient was 58 year old with no major comorbidities.

If the patient is HPV negative would you do radiation alone?

In case of HPV negative or smoker or multiple nodes we add ChT. We do Cisplatin weekly 30 mg per ms. It is considered wimpy and it is not toxicity free. Anyway it is a very tolerated program. It gives the opportunity to stop it quicly if toxicity is developing.

You may work in an institution where the surgeon pushes for TORS. For stage III TC the LC control probability would be the same for radiation and TORS. The main issue in this case is the significant involvement of the palate. I would ask the surgeons if they suggest TORS in such a case. If there is involvement of the palate what would the surgeon expect form the functional deficit that results from resection. This involvement of the palate is a strong argument for RT against TORS.

This patient at Dana Farber would receive chemo RT.

Would you treat the contralateral nodes.

I would treat them mainy due to the significant involvement of the palate. If there is no involvement I would not treat the contralateral neck.

This case is on the border line as only the lateral third of the palate is involved. I would treat the contralateral nodes.

The pattern of the lymphatic drainage of the palat is siilar to that of the tongue. Small lateralized lesions do not have contralateral lymphatic drainage but deeper ones do. These lesions do not need to go to the midline to get to the contralateral lymphatics. Deep tongue cancers put at risk the contralateral neck. The drainage of the palate is similar to the tongue.

Do you think that the contralateral neck can be salvaged with an operation later. From the tongue data the risk of dying from contralateral neck disease is very small. Less than 2% of these patient will have a salvage neck dissection.

I think that we are overtreating the contralateral neck in this patient. The risk of contralateral neck failures is less than 10% in these patients. We put the patient at a life long morbidity by treating the contralateral neck.

In our data the salvage rate is almost zero.

It is a very well lateralized small tonsil cancer but it is a N2b. Do you treat the contralateral side or not.

If it is a bulky N2b I would treat it. If it is a small N2b. If you go to the Toronto and the Vancouver data a very small number of patients had significant N3 disease. The question is can we compare our IMRT HPV data to the Toronto data. There are 2 confounding issues. One is in Toronto when they treat the neck they use a wedge pair with an exit dose of 20 Gy to the contralateral neck. Now with IMRT the dose is much lower. Secondly patients with HPV related cancer have more extended LN mets compared with old series. So the risk of contralateral neck involvement may be higher in HPV cancer.

Yesterday we heard data from Rotterdam where they treated early tonsil cancer with IMRT without treating contralateral neck. Patients did very well. They included 46 patients with palate cancer. One had a contralateral neck recurrence.

The contralateral neck should exclude level 1b.

Would you do a PET to determine the need to treat the contralateral neck. I do not use PET except for looking for distant mets. I do not use it for contouring at all.

If PET is negative in the contralateral neck would you not treat it.

On PET we do not see anything less than 3 mm.

Woud you accelerate the RT dose program. I do always. I do RT in 6 days with one day BID.

Second case: 55 year old woman. Otalgia, dysphagia and sore throat. She had a tumor in the right posterior pharyngeal wall extending to the level of the soft palate. From the soft palate to the adenoid region with possible surrounding sub mucosal extension. She was found to have a 8 cm mass, fixed to the pre – vertebral muscles. She has a history if hypertension. She is a smoker, 30 pack year, she recently quit. We were not checking HPV status on our patients at that time. Stage is T4 N0 M0. 

The question for you is how would you treat this patient that has locally advanced HN cancer. Surgery followed by radiation or CRT, chemo RT with bolus Cisplatinum q 3 weeks and then RT, induction ChT with D C 5FU for 3 cycles followed by concurrent CRT, weekly carboplatinum and paclitaxel with daily RT.

58% voted for CRT with bolus cisplatinum, a third would use induction ChT with TPF followed by CRT, 10% would not use cisplatinum here, a minority would operate. 

In Boston we gave this pt a TPF followed by CRT. She completed ChT in april 2003. At that time we were not using IMRT. She was treated with conventional radiation, dose of 70 Gy and then weekly carpoplatinum. She had a CR. 

She was followed routinely over 10 years with no recurrence, then in june 2012 she developed right otalgia and sore throat. She had a leukoplachia lesion to the right tonsil that is firm to palpation and is confined to the tonsil. It does not extend to the palate or tongue base. She has no trismus. She has fibrosis in the neck. She does have a CT scan which confirms a small tonsillar lesion (8 mm) with no neck adenopathy. We staged it as a T1 N0.

How would you treat this pt in your practice. Would you do a TORS. Would you give radiation to the tonsil and the ipsilateral neck. Would you give RT to the tonsil only. Would you do TORS plus neck dissection. 

51% of the audience would operate. 38% would operate and at the same time do a neck dissection. 

We decided to treat this pt with TORS. On final pathology she has a 2.2 cm mass. Margin is negative. There is no LVI and no PNI. She is a pT2 N0. We operated only on the primary and not on the neck. HPV status is negative by p16 and ESH. 

What would you do right now for this woman who is now 64. Would you do a bigger operation to get a bigger margin plus a ND, would you do just a ND now, would you do radiation to the primary site, primary site and neck, would you give this woman concurrent CRT.

We have a parity here for 1 and 2. Some of you would take this pt back to the OR for more surgery, including primary and neck. 32% would do an ipsilateral ND. We did a ND only. She was pN0. 

This is an interesting case of second primary tumor 10 years after sequential therapy. I want to show some more slides. We treated this woman with this regimen. This is the 324 study which compared 2 induction ChT regimens (D, P, 5FU - P, 5FU) followed by carboplatinum - radiation. 

This study included patients with OP primary (more than 50%) in good PS who entered the study because they were unresectable, or they had low surgical cure or they were included for organ preservation. This study essentially showed that if you add D to P - 5FU you do better than P - 5FU, you improve survival and PFS. 

We published last year the 5 year update of this study which continue to show that TPF is superior to PF with an improvement in survival. There are 2 other studies showing also that TPF is better than PF. So the message is that if you use induction ChT you should be using TPF; that is the standard induction ChT regimen. 

The bigger question in treating these pts is what is the role of in induction as a modality for treatment. You need induction ChT for those pts to improve survival. For those of you who went to ASCO this year there were 2 presentations comparing sequential to concurrent CRT for HN cancer (locally advanced disease). Both of these studies were not accounted for HPV (there was no stratification for HPV). Both of these studies did not complete the planned accrual and were both underpowered. They both did not show any advantage of one regimen versus the other. There were no differences between sequential and concurrent CRT. 

This is the DECIDE trial that has a particular concurrent CRT regimen. This is a BID radiation with D, 5FU. Like our study, the DECIDE study showed no advantage for induction ChT in these pts. 

These are some scenarios I would use to consider induction ChT for my pts. We can debate this. 

This pt did very well, she responded well to treatment and has a good QOL. I think this pt has 2 options for treatment, concurrent CRT and sequential CRT. To me these 2 options are completely appropriate for  a pt with T4 OP cancer. I would agree that many people would consider concurrent CRT the level 1 evidence and standard of care. I think we have enough evidence with phase III studies with sequential treatment which is also an effective modality for treatment Unfortunatey DECIDE ans PARADIGM were underpowered to answer this important question. I would consider sequential CRT to be an appropriate therapy for pts like this one.

We have to be careful about whom we select for this approach, about PS and comorbidity. TPF regimen has its own side effects. But in carefully selected pts with PS 0 - 1, those toxicities are manageable. IN my opinion this pt would have these 2 options for treatment, they are both appropriate, they were appropriate in 2002, they remain appropriate today. 

Would you do induction in your institution in this pt.

No. This is a reirradiation case. 

What about the first scenario.

You mentioned the most important ChT issue trials for 10 years or so in 2 slides. I think that the role of neoadjuvant ChT is in a pt that is too bad off to start RT, meaning that the only pts that I treat with neoadjuvant ChT are the people that about to die of malnutrition and can not lay down on the table. 

The best treatment is concurrent CRT with accelerated RT. If this T4 pt was such that, they are unable to handle their secretion. They need a feeding tube tomorrow. They were metabolically out of control. We need weeks of management. I would talk with my medical oncologist and he unhappily agrees to start neoadjuvant ChT. Otherwise we would treat this pt with accelerated 2 weeks RT with concurrent ChT. 

The other aspect of the case was should recurrence be treated with surgery or reirradiation or reirradation plus ChT The audience showed surgery in those pts who are resectable at recurrence. 

Would you do any different in a pt who is resectable or is resection likely to result in significant functional deficit so sometimes we decide differently in such patients. 

This reirradiation case is a great case as it represents what we are challenged with. In our weekly tumor conference we have 10 pts and at least 3 ones are reirradiation questions. If you take all the publications and you see what is the value of reirradiating a second primary in HN cancer with high dose field like this case, there are many papers encouraging reirradiation. My opinion is that they are all meaningless Reirradiation is a disaster. It causes complications. We treat highly conformal only to the GTV plus a cm. We do not deliver any elective nodal treatment. We are doing a publication where the failure rate in the elective nodes in people previously irradiated is low. I reirradiated one pt and he had every possible late long term toxicity (cranial nerve deficit, mandibular necrosis) but he was cured from reirradiation. In this case I would have done only surgery. 

In you reirradiation protocol is there any role for BT.

In the literature if you look at BT for reirradiation the risk of soft tissue damage is higher than in EBRT. There are new technologies like hypoF, with 5 or 6 fractions, Assuming that larger F will overcome the resistance to radiation. The biological risk of complications may be higher even if you are very tight to the tumor. So far the data that have been published on hypoF do not suggest any better local control than others. I would like to add that in our experience we treated gross disease with close margins. All loco regional recurrences were within the gross tumor. This is because the rate of local control is so low so you do not have the opportunity to see loco regional recurrence. You can have 5 year survival of 30%. The risk of complications is 30%. Mucosal complications are the largest ones. Carotid blow out can be due to tumor progression. 

Following the second primary resection the margin were clear. So why did we do ipsilateral ND. It was  T2 and we thought it was a T1. 

The neck was addressed previously by irradiation but as new cancer arose the neck is again at risk. The highest risk is in the previously dissected neck where for sure any recurrence will be non salvageable by surgery. In this case the ipsilateral neck was not dissected before so ipsilateral ND should be tee good option now. 

Given an excellent response to induction TPF, would you treat a smaller volume or to a lower dose of radiation. As a medical oncologist I would tell you no. We do not modify how we give radiation base on how the pt responds to induction. That too is a research question. There are trials like the ECOG study, which is completed now. In HPV positive pts it asks the question of induction first. If you have a CR or a good PR you get 54 Gy of radiation with ChT but that is a study question. At this stage if you are using induction ChT you should not be giving less or more radiation based on the response. 

I struggle with that in pts that are being managed with induction ChT. I do not change the volume based on the response to induction ChT. I think it is not a satisfying situation. 

This question is parallel to the question what do we do during radiation. We have CBCT, we see the tumor shrinking. Should we shrink the GTV. We shrink the GTV after induction ChT, should we shrink GTV during radiation. 

This is a 33 old female with intermittent recent blurred vision and headache for 2 - 3 weeks. No significant PMH. Left sixth nerve palsy. In radiology we see a large tumor in the nasal cavity and sinuses invading the orbit, invading the dura with extension into the brain. Biopsy showed a sino nasal undifferentiated adenocarcinoma. 

What is the best treatment option in this unresectable case. Steroids started right away. The question is what to do now. 1 - starting ChT cisplatinum - VP16 for 1 - 2 cycles aiming to shrink the tumor to allow better sparing of the optic nerves by irradiation. 2 - ChT may not be fast acting therefore we need to start radiation alone to avoid a higher optic nerve toxicity form CRT. 3 - start CRT. 4 - start CRT concurrent with amifostine which is known to reduce optic nerve toxicity. 

We decided to go concurrently. High dose cisplatin - VP16 q 3 weeks. Concurrent radiation. The CTV1 was the MRI based tumor plus edema in the brain part plus 1.5 cm margins tighter near the optic nerves. PTV was 3 mm extension assuming that every day we do imaging to check set up uncertainties. This extension was tighter near the optic nerves. We started with 2 Gy times 5 using 3D because we had to start right away. In the meantime we planned IMRT and we gave additional 40 Gy to a total of 50 Gy. The plan was to review tumor shrinkage and possibly modify the target after 50 Gy. 

We treated just the primary. The risk of LN mets is about 15% but due to the extensive primary tumor and the feeling that our chance to control it was not that high we decided not to treat the LN profilactically. 

This is the IMRT set up. 

This is the dose distribution. 

After 50 Gy we did MRI which showed significant regression of the GTV. The optic nerves which previously were pushed to the side by the tumor extending to the orbit are now back straight. The tumor is likely away from the optic nerve. It is much easier now to spare the optic nerves if we continue with the new GTV. 

Here is the question. If the tumor shrinks substantially at mid therapy, should the primary GTV1 routinely be modified. Shall we do a new IMRT plan sparing more tissue. Or modification of the GTV and a new planning should not usually be done. 

We decided to shrink. The cumulative dose is 70 Gy, while 54 Gy treat the old GTV. 

Should we treated this pt with protons. 1- protons would cover the target and spare the optic nerve better than IMRT. 2 - it is not necessarily so. 

SNAC. If resectable (no involvement of the brain), cranio facial resection followed by adjuvant CRT or CRT followed by resection are the standard. If non resectable like this case either ChT followed by CRT or CRT The problem is that we do not have data. In the literature the typical series is less than 10 pts. With larger series of 16 - 17 pts no consistent treatment. No conclusions can be done by the literature. 

What about doses. In U Florida data 2 of 4 pts receiving 70 Gy concurrent with ChT were locally controlled. 50% of pts receiving 70 Gy are NED. In australia the results are stronger. 100% of pts receiving 60 Gy concurrent with cisplatin are NED. This is what we have. So 70 Gy control 50%, 60 Gy control 100%. This is a reflection of the lack of data. 

If you look at the treatment of sino nasal tumors SNAC is in the middle. Esthesioneuroblastoma is much better. Neuroendocrine tumors and SNAC are doing about the same. Small cell cancer of sino nasal cavities to the worst. 

For small tumors LN  should be treated if you have good chance of local control. 

What about shrinkage of tumor following either ChT or radiation. 

Some canadian medical oncologists introduced induction ChT during the late 80s when induction ChT was really hard. When we get a CR we get 1 or 2 logs out of 9. This is the argument why neoadjuvant ChT in the 80s did not translated into better survival even though we saw a CR. We have some subclinical disease. This as far as reducing GTV if we have response to induction ChT. We should not. 

The same happens during radiation. We know that tumor shrinks during radiation and so LN. Now we see it at CBCT. At 50 Gy we do not see the edges of the cancer any more but we killed 1 or 2 logs out of 9. 

In this case there is benefit to shrink the GTV which is getting off the optic nerve. In general my suggestion is do not shrink the GTV whether after induction ChT or during radiation. 

Protons. Most of the studies comparing IMRT and protons are done in the same institution like U Florida. The report are that protons are better. There is conflict of interest. 

We made a poster with 2 institutions (I am not speaking about IMPT which is a different story). Protons have no advantage over good IMRT for base of skull. 

We will publish a poster for next ASTRO. My proton colleagues in my institution will disagree with you. There are small changer in how you contour the target. It is difficult to say what is an important dosimetric difference. There are always parts of the DVH that look better with one technique versus another especially with heavy particles. There is no question that if you want to find a positive result with proton you always can because there is nothing like protons when it comes to low dose bath.