IntensityModulated Radiation Therapy IMRT in the Treatment of Cancer of the LarynxHypopharynx

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Intensity-Modulated Radiation Therapy (IMRT) in
the Treatment of Cancer of the Larynx/Hypopharynx

• Kelvin Chan, B.A., William P. OMeara,
  M.D.,Joanne Zhung, B.A., James G. Mechalakos,
  Ph.D.,Suzanne Wolden, M.D., Ashwatha
  Narayana, M.D., Dennis H. Kraus, M.D..,
  Jatin P. Shah, M.D.,David G. Pfister,
  M.D., Nancy Y. Lee, M.D.

Department of Radiation OncologyDepartment of
Medical PhysicsDepartment of Surgery Head
Neck Service Department of Medicine Head
Neck Service
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Background

• Established by multiple randomized trials and
  RTOG 91-11, concurrent chemoradiotherapy offers
  the best chance of organ preservation for
  patients with advanced laryngeal and
  hypopharyngeal cancer.
• However, toxicity reported by patients who
  undergo concurrent chemoradiotherapy should not
  be underestimated.

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Background

• Due to the inability of conventional
  radiotherapeutic techniques to spare the parotid
  glands, patients often complain of permanent
  xerostomia. This is especially seen in patients
  who present with bilateral lymphadenopathy.
• IMRT has the ability to target the gross tumor
  more precisely while minimizing the radiation
  dose delivered to the surrounding normal tissue
  such as the parotid glands. As a result, there
  is a good chance that patient salivary function
  can return over time.

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Purpose

• This is a retrospective review of Memorial
  Sloan-Kettering Cancer Centers experience in
  treating laryngeal and hypopharyngeal squamous
  cell carcinomas with IMRT.
• The purpose is to ascertain whether the use of
  IMRT demonstrates comparable local control of
  disease as well as decreased rates of late
  toxicities such as xerostomia.

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Materials and Methods

• Time frame of study - January 2002 June 2005.
• 83 patients presented with larynx or hypopharynx
  cancer and underwent external beam radiation
  therapy at MSKCC.
• 46 patients received conventional radiotherapy
  and were excluded.
• Stage I 20, Stage II 8, stage III/IV 18
• The remaining 37 patients received IMRT and
  represents our cohort.

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Materials and Methods
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Materials and Methods
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Materials and Methods

• Radiation TherapyIMRT with Dose-Painting
  Technique - N 31

• Concomitant Boost Technique (54 16 Gy)- N 5
• Post-operative IMRT (60 Gy) - N 1

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Materials and Methods

• Analysis of Dose-Volume Histograms

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Materials and Methods

• Dosage to Critical Structures
• Max point doses to brain stem, spinal cord and
  R/L cochlea were 52 Gy, 46 Gy, and 37/37 Gy
  respectively.
• Mean doses to right and left parotid glands were
  25 Gy and 26 Gy respectively.
• Max, D05 and mean doses to the glottic larynx
  were 78 Gy, 77 Gy and 75 Gy respectively.

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Materials and Methods
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Materials and Methods
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Materials and Methods

• ChemotherapyConcurrent Chemotherapy - N 33

2 patients switched to Carboplatin/5-FU for 1
cycle, 1 patient received only 1 cycle of
Cisplatin due to bone marrow intolerance 1
patient switched to weekly Carboplatin/Taxol, 1
patient received only 1 cycle of
Carboplatin/5-FU due to persistent
pancytopenia 1 patient received only 1 cycle
due to neutropenia and sepsis All 4 patients
did not have nodal involvement
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Materials and Methods

• Surgery - N 3
• 1 patient underwent laryngectomy (at an outside
  institution) and thought to have larynx-confined
  disease, but found to have residual and bilateral
  neck disease and referred for definitive IMRT.
• 1 patient underwent a neck dissection prior to
  treatment but was found to have gross disease
  involving the piriform sinus and referred for
  definitive IMRT.
• 1 patient underwent surgery (laryngectomy and
  neck dissection) then post-operative IMRT.

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Results

• Overall Population
• Median Follow-up Time 22 months (range 7
  55 months)
• Living Patients
• Median Follow-up Time 24 months (range 16 -
  55 months)
• 6 patients had local recurrence (4 larynx, 2
  hypopharynx).
• All 4 patients with local failure of laryngeal
  carcinoma had persistent disease at the end of
  treatment.

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2-yr Local Progression-Free Survival
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2-yr Regional Progression-Free Survival
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2-yr Locoregional Progression-Free Survival
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2-yr Distant Metastasis-Free Survival
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2-yr Overall Survival
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Results

• Concurrent Chemoradiation Subset
• Larynx 21 patients
• Hypopharynx 12 patients

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2-yr Overall Survival - Larynx vs. Hypopharynx
Patients (CCRT only)
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2-yr Overall Survival - LRP-Free vs. LRP-Failure
Patients (CCRT only)
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Results

• No patients underwent elective neck dissection
  after definitive chemoradiotherapy.
• 5 patients subsequently underwent salvage
  surgery
• One T3N2b piriform sinus cancer patient had
  resolution of his primary disease but had
  persistent neck mass as the end of treatment and
  underwent neck dissection.
• 3 larynx cancer patients had persistent
  locoregional disease and underwent laryngectomies
  and neck dissections
• 1 larynx cancer patient underwent laryngectomy
  and neck dissection for pathologically-proven
  radionecrosis.

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Results

• Acute Toxicities Reported

Acute and late toxicities were scored using the
RTOG radiation morbidity scale.
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Results

• Late Toxicities Reported

Acute and late toxicities were scored using the
RTOG radiation morbidity scale.
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Results

• In general, the treatments were well tolerated.
• Of note, acute toxicities of grades 4 and 5 were
  not seen.
• Xerostomia continued to decrease over time from
  the end of RT.
• Only 4 patients complained of late Grade 2
  xerostomia.
• One patient developed laryngeal necrosis and one
  developed Grade 2 trismus.
• Both received concurrent carboplatin/5-FU.

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Results

• 35 patients received prophylactic feeding tubes
  (PEG)
• Prior to IMRT 32, During IMRT 1, After IMRT
  2
• 2 patients did not require PEG tube at any time
  (and did not receive chemotherapy).
• A greater proportion of patients with hypopharynx
  cancer were still PEG-dependent post 1 year of
  treatment.
• Laryngeal carcinoma 39 (n 6/23)
• Hypopharyngeal carcinoma 56 (n 6/12)
• Median time to PEG removal 4 months from
  completion of RT.

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PEG Dependency Rates - Larynx vs. Hypopharynx
Patients
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Conclusions

• IMRT, in combination with chemotherapy, achieved
  encouraging local and regional control rates.
• Xerostomia improved over time.
• Pharyngoesophageal stricture with PEG dependency
  remains problematic in patients especially for
  hypopharyngeal carcinoma.
• Strategies using the ability of IMRT to limit the
  dose delivered to the esophagus and inferior
  constrictor musculature may be useful to further
  minimize this late complication.