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.

Prostascint Scans

MP presents on the utility (or lack thereof) of Prostascint

Prostascint is based off of a PSMA (prostate specific membrane antigen) antibody - capromab.  FDA approved in 1996 for diagnosis and staging in high risk disease and for PSA recurrence after RP.

The scan is performed by In-111 conjugated capromab.  Scan is performed with Tc99m to differentiate pathologic uptake from vasculature.  Recently these have been fused with CT or MRI.  Cost per scan is ~2,000$

Pt presented with intermediate risk disease (GS 3+4 with organ confined disease treated with prostatectomy, with persistent PSA of 0.3ng/ml postoperatively).  A prostascint is obtained and reveals paraaortic uptake without CT correlate, and no activity in the prostate bed.

Test Characteristics.

Sensitivity - true positives/true positives + false negatives

Specificity - true negatives/true negatives + false positives

Elgamal - 100pts with 136 scans.  124 has positives prostascints - all positives were biopsied, and some of the negatives (though this was not well controlled)

Sensitivity - 89%

Specificity - 67%

Bone scan didn't correlate well the Prostascint (sensitivity of prostascint was only 57% for bone scan positive disease)

Multiple studies exist demonstrating a wide range of sensitivity of 36-86%

Raj Cancer 2002 - 222 pts with early biochemical failure after surgery.  174 scans were positive.  False negative rate was 31% in this cohort.  Sensitivity of a subset was 73% and specificity of 53%, PPV 89% - however they utilized response to RT and later progression as the gold standard.

Kahn JCO 1998 - 32pt treated with 60GY postoperatively.  5 negative scans, 18 has bed only, 9 had distant disease.  Prostascint didn't dictate therapy in this case.  Durable clinical response (DCR) was rare in those with distant uptake (27%).  In those with prostate bed uptake DCR had a 62% DCR rate and 88% in those with no uptake.  Some were biopsied in the bed - sensitivity was 78%, specificity 7%.

Proano J Urol 2006 - 44 pts with biochemical recurrence after RP - salvage RT used in all, nodal basins were radiated when Prostascint positive in nodal basins.  41% with a positive scan progressed vs 10% with a negative scan.  Data presented however without KM(Kaplan Meier) estimates.

Nagda IJROBP 2007 - 58 pt with prostascint scan after biochemical recurrence after RP.  Salvage RT used in all.  No difference in any of the prosascint results (distant uptake, bed uptake, or no uptake).  KM estimates used.  Sensitivity 30%, Specificity 58% (using recurrence as the gold standard for presence of disease)

Thomas JCO 2003 - 30 pts with biochemical recurrence after RP.  Prostascint positivity not predicitive of biochemical recurrence.

Koontz IJROBP 2008 - pooled data from some of the above trials - no difference in outcomes dependent on prostascint.

Case outcome - Prostascint results were not utilized in determining treatment - Salvage RT was delivered to 66Gy.  Pt also seen by medical oncology - they agreed with the assessment.  Pt had a complete biochemical response to RT.  Note: patient was treated where scan was negative, and not treated where positive, and a biochemical response was seen.