Thursday, April 16, 2009

Reirradiation for Reccurrent H&N cancer

AC presents today on a case of recurrent nasopharyngeal cancer, treated initially with 65Gy in 1992. Pt experienced Lhermitte's sign (shooting shock like sensations, particularly with neck flexion). - Of note this is not associated with the later development of myelopathy.

in 2007 developed R ear fullness and decreased hearing. CT scan demonstrated mass in the R parapharyngeal space, extending superiorly to the sphenoid sinus and invasion into the clivus. There was also opacifation of the R mastoid air cells. MRI confirmed mass. Biopsies were only positive for radiation change.

in 2008 mass progressed, and at this time the mass was biopsy positive for recurrence NPC.

15-50% of H&N cancers develop local failiures. Incidence of 2nd primary tumors is around 14%, with 1/3 of these in the H&N. (note that with NPC often recurrences are distant, and can be quite delayed).

Options include resection +/- RT, Reirradiaiton +/- CT, or palliative chemo. MS is <10 months, OS at 1 year is less than 35%.

Surgical salvage results in 5y OS of 10-25%. Operative mortality close to 5% (Goodwin, Laryngoscope 110:1, 2000.)

Reirradiation is primarily limited by normal tissue tolerance (carotid artery stenosis/rupture, osteoradionecrosis, non-healing ulceration, myelopathy). Disease free intervals of less than 6months suggests persistent disease, likely resistant to the initial treatment regimen.

Approach includes review of the initial treatment portals: was there a geographic miss? What were the doses to normal tissues.

Non-randomized series of postoperative RT after resection (in highly selected patients) result in 3y OS of approximately 44% (Kasperts Cancer 2006;106:1536. also De Crevoiseier Cancer 2001;91:2071.) Acute Grade 3-4 toxicities are around 50% reported, late effects are near 40%, but likely these are underreported. Actuarial calculations are lacking in this, and are a necessity for a true accounting.

Janot JCO 26:5518, 2008 - GORTEC group. 130 with complete resection after recurrence - randomized to observation vs 60Gy BID, with 5FU + HU (week on, week off style Chicago regimen). - Acute mucositis G3-4 28%. Late G 3-4 toxicity in the RT arm was approximately 40%. HR for LRC for RT was around 2.7 (60% at 2years for RT arm, SS), but no difference in overall survival. DFS was statistically improved and was the primary endpoint. Note that around 1/2 of the observation arm recieved salvage treatment with the same regimen, and this would dilute the OS benefit.

RTOG 9911 Langer JCO 25:4800, 2007. n=99. Recurrent unresectable cancer in prior RT field. Recieved 60Gy 1.5Gy BID with concurrent CDDP + paclitaxel (week on week off). Median f/u 24months. Acute grade 4 at 28%. Grade 4 late toxicity 17%, 8 treatment related deaths, many of these carotid rupture. 2yr OS 26%. Able to achieve a maximum dose to cord of 12Gy.

Sulman IJROBP 73:399, 2009. MDA series using IMRT in 78 patients. 2yr OS 58%, 2 yr LRC 64% (though many of these were recurrent and resectable). Median reirradiation dose was 60Gy.

Also MSKCC series (Lee, IJROBP 68:731, 2007), showed 2 yr OS 37%, with 70% treated with IMRT. Late toxicities at 15%. MVA showed association with improved LRC with IMRT (but this has some leadtime bias built in). Around 1/3 were treated after re-resection.

To return to the case - prescribed 70Gy to the tumor alone, with very tight margins close to 1-2mm, with daily OBI, weekly conebeam. Treated 6 fractions per week (ala DHANCA) with concurrent CDDP. No elective treatment due to the risk of severe morbidity.

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