IGRT uses a range of two-, three-, and four-dimensional imaging techniques that improve the precision and accuracy of the delivery of the radiation dose to the targeted tumor tissue while minimizing the dose to the surrounding normal tissue during the course of radiation therapy (Figure 1).
In this report, we present challenging cases of advanced tonsillar carcinoma and describe our experience in managing the disease using a hyperfractionated IMRT-IGRT based three-dimensional conformal radiation therapy protocol with concurrent chemotherapy.
Case Presentations and Summaries
Case 1
A 52-year-old white, nonsmoking man who worked in a research chemical laboratory presented with complaints of throat pain and difficulty in swallowing. The patient had a history of asthma and allergies and had been seen by an ear, nose, and throat (ENT) specialist prior to his visit to our oncology center.
A biopsy was performed on a right tonsillar mass measuring 2.7 x 3.6 cm. A computed tomography (CT) scan showed 2 enlarged inhomogeneous lymph nodes measuring 2.9 cm and 1.7 cm. The nodes were well defined with no soft tissue edema. Neoplasm was favored as a diagnosis, and a biopsy of the mass was carried out. A biopsy specimen measuring 1.0 x 0.4 x 0.3 cm revealed a moderately differentiated infiltrating squamous cell carcinoma, which extended to the edge of the biopsy specimen.
The patient’s Karnofsky performance status was 90% (i.e., able to carry on normal activity; minor signs or symptoms of disease). A CT scan of the chest was clear with no evidence of malignant involvement. A subsequent CT scan of the neck revealed a primary neoplasm of the right faucial tonsil measuring 3.3 x 3.0 cm and associated with right level II, level III, and level IV pathological lymphadenopathy. Positron-emission tomography (PET) imaging of the neck revealed a right tonsillar lesion of 2.7 x 3.0 cm involving the right parapharyngeal space (Figure 2, Case 1).
The standardized uptake value (SUV ) of the PET scan of the primary lesion was measured at 7.3. A cluster of right level II cervical nodes measuring 3.2 x 2.5 cm had an SUV of 3.5. A 1.0-cm right level III jugular node was also seen with an SUV of 1.6, and a right level IV lymph node measuring 1.5 x 1.0 cm was seen with an SUV of 1.8. No other lesions were noted. The tumor stage was T2N2bM0, a stage IVa disease. The patient had a percutaneous endoscopic gastrostomy (PEG) tube placement before starting radiation.
He underwent a course of hyperfractionated intensity-modulated radiation therapy with image guidance (IMRT-IGRT) in 67 fractions of 120 cGy twice a day to a final tumor dose of 8,040 cGy.
Concurrently, the patient received systemic chemotherapy with carboplatin at a dose of 240 mg weekly. To optimize the treatment, molecular profiling was performed to identify the sensitive genetic targets to systemic chemotherapy drugs.
Targets sensitive to paclitaxel and docetaxel were identified by molecular profiling of the tumor tissue, then chemotherapy with paclitaxel or docetaxel (25 mg/m2 weekly for 3 weeks and 1 week off ) was also administered to the patient.
The follow-up after 41 months indicated that the patient had no evidence of recurrent disease (Figure 2, Case 1). Posttreatment magnetic-resonance imaging (MRI) of the neck also indicated no evidence of residual tonsillar cancer. The patient’s demographics, tumor characteristics, and treatment details are summarized in the Table.
Case 2
A 49-year-old black male presented with throat pain, and a mass is seen initially by his family physician. The patient had a history of tobacco use (at least 1 cigar a day) periodically for about 10 years and had quit cigar smoking 15 years prior to developing his disease.
An initial evaluation indicated that the patient had a hypopharyngeal mass in the left inferior pole of his tonsil with near occlusion of the hypopharyngeal airway. His larynx could not be visualized because of the obstructive mass. A neck lymph node measuring 3.0 cm in the left jugulodigastric region was also noted. The patient’s Karnofsky performance status was 90%. Subsequently, the patient underwent excision of the right tonsil and left the tonsillar region. The pathology of the right tonsil was found to be benign. Histology of the left tonsil revealed invasive squamous cell carcinoma.
The resected tumor size measured 3.7 x 2.7 x 2.5 cm. The tumor was moderately differentiated, involving the deep surgical margins. No lymphovascular invasion was seen. A PET scan revealed a mass arising from the left tonsillar pillar measuring 3.6 x 2.6 x 3.3 cm with a deviation of the epiglottis posteriorly nearing the left vallecula. In addition, multiple large cervical nodal lesions in the left level II nodal chain were seen, with the largest measuring 3.1 x 3.0 x 4.5 cm with an SUV of 3.4.
Displacement of the left submandibular gland with several further enlarged level II lymph nodes was observed. In the region of the left vallecula, there was soft tissue thickening with increased activity measuring 2.7 x 1.5 cm, likely crossing the midline with an SUV of 5.5. The rest of the neck was negative for metastatic involvement (Figure 2, Case 2). The tumor stage was T3N2Mx, a stage IVa disease.
The patient had a Port-A-Cath placed, which caused a hemothorax after placement of the port and delayed initiating his treatment. A pretreatment MRI scan of the neck revealed multiple conglomerate hypodense peripherally enhancing nodular areas in the left neck posterior to the left submandibular gland deep to the parotid tail worrisome for necrotic lymphadenopathy. The patient underwent a course of hyperfractionated IMRT-IGRT in 67 fractions of 120 cGy twice daily for a total dose of 8,040 cGy to the primary tumor site.
The patient had a port and PEG tube prior to initiating his radiation therapy. He received IMRT-IGRT with concurrent chemotherapy that was selected based on the recommendation of his genomic testing.
The chemotherapy regimen used included carboplatin (300 mg weekly) and docetaxel (400 mg weekly). The patient had a treatment break because he was hospitalized for anemia and pancytopenia from his chemotherapy, and he received supportive cancer care with epoetin alfa.
A post-therapy PET scan was negative for evidence of hypermetabolic malignancy; however, a 3.3 x 2.7 cm calcified lesion representing likely level III jugular lymph node exhibited no measurable activity at that time.
The follow-up after 40 months indicated that the patient had no reported recurrence of the disease (Figure 2, Case 2). The patient’s demographics, tumor characteristics, and treatment details are summarized in the Table.
Case 3
A 53-year-old white man, who had no smoking or tobacco history but who was exposed to chemicals including sulfuric acid, hydrogen chloride gas, and glycols at work, presented initially with a sore throat that became more painful over time.
His ENT specialist referred him for a CT scan of the neck, which revealed a left-sided neck mass measuring 2.5 cm in diameter posterior to the submandibular gland and lateral to the carotid sheath and anterior to the triangle (Figure 2, Case 3). The mass appeared to be encapsulated. There was a lobulated spherical mass in the left supraglottic area with the formation of the airway of the pyriform sinus, and additional anterior vascular involvement was noted. The mass measured 3.6 cm in transverse diameter.
A left tonsillar biopsy specimen measuring 1.4 x 0.6 x 0.2 cm was obtained, and its pathology revealed that the patient had a metastatic squamous cell carcinoma. The left neck lymph node mass aspiration also revealed the presence of squamous cell carcinoma. A PET-CT scan staging showed a dominant tonsillar fossa mass extending from the soft palate down to the pyriform sinus measuring 4.2 x 3.8 cm, with an SUV uptake of 7.3.
There was a dominant left level II necrotic lymph node presence measuring 5.0 x 3.7 cm, with an SUV of 3.0. The patient’s Karnofsky performance status was 90%. The tumor stage was T4N2M0, a stage IVa disease. The patient received a course of conformal hyperfractionated IMRT-IGRT delivered to the primary tumor in 67 fractions at 120 cGy twice daily for a total dose of 8,040 cGy16 and concurrent carboplatin chemotherapy at a weekly dose of 200 mg.
Following completion of his radiation therapy, chemo-therapy was changed based on genomic testing from a single agent to doublet with carboplatin (area under the curve (AUC) dose of 2 or 200 mg, weekly) plus docetaxel (25 mg/m2 weekly for 3 weeks and 1 week off).17,18 A PET scan after his chemoradiation therapy revealed a marked anatomical improvement in the primary neoplastic disease seen in the faucial tonsil.