Personalized Management of the Neck in Cancer of the Upper Aerodigestive Tract: Radiotherapy to the PRIMary Tumor Only (PRIMO)
Study Details
Study Description
Brief Summary
Squamous cell carcinomas of the oropharynx, larynx and hypopharynx are generally treated with (chemo)radiotherapy for reasons of organ preservation. There is a substantial risk of neck lymph node metastases that, if present, negatively affect prognosis. Because historically, diagnostic work-up had limited accuracy for the detection of small lymph node metastases (microscopic metastases), not only the primary tumor is irradiated but also elective irradiation of large anatomical volumes of the neck is performed routinely to eradicate undetected nodal tumor deposits. Most toxicity and permanent long-term radiation side effects are caused by elective neck irradiation because the irradiated tissue volume is much larger than what is necessary to treat only the primary tumor. These side effects are notoriously known to negatively and permanently affect quality of life. Despite recent advances in diagnostic imaging, the detection of very small lymph node metastases is still insufficient to omit elective neck irradiation.
Sentinel lymph node biopsy is a standard procedure in surgically treated patients to reliably identify microscopic metastases by histopathological examination in first draining lymph nodes (sentinel lymph nodes). The technique is based on the premise that metastases orderly progress with the lymphatic flow from the primary tumor to the sentinel lymph node before spreading to subsequent draining lymph nodes, and that the pathologic status of the sentinel lymph node accurately reflects the histology of subsequent lymph nodes. However, sentinel lymph node biopsy is not yet employed routinely in head and neck cancer patients treated with (chemo)radiotherapy. When elective neck irradiation would be tailored to the individual patient guided by information provided by sentinel lymph node biopsy, elective neck irradiation will not be necessary for the majority of patients. This will reduce the morbidity of treatment enormously with substantial better quality of life after treatment.
The primary objective of this multicenter, randomized controlled, phase III, combined non-inferiority and superiority trial is to evaluate the safety and efficacy of sentinel lymph node guided selective elective neck irradiation compared to standard elective neck irradiation.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sentinel lymph node biopsy guided selective elective neck irradiation FDG-PET-scan in treatment mask for radiotherapy planning Sentinel lymph node biopsy Radiotherapy (IMRT/VMAT with SIB) to the primary tumor with selective elective neck irradiation guided by histopathologic status of the sentinel lymph node(s) |
Radiation: Sentinel lymph node biopsy guided selective elective neck irradiation
Patients will undergo sentinel lymph node biopsy. Based on the histopathologic status of the sentinel lymph node(s), selective elective neck irradiation is performed with standard radiation treatment of the primary tumor.
There are 3 possible treatment scenarios.
Bilateral elective neck irradiation is indicated when sentinel lymph nodes at both sides of the neck contain metastases or when sentinel lymph node detection fails.
Unilateral elective neck irradiation is indicated when sentinel lymph node(s) at one side of the neck contain metastases.
Full omission of elective neck irradiation is indicated when all sentinel lymph nodes are free of metastases.
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| Active Comparator: Standard elective neck irradiation FDG-PET-scan in treatment mask for radiotherapy planning Radiotherapy (IMRT/VMAT with SIB) to the primary tumor with standard elective neck irradiation |
Radiation: Standard elective neck irradiation
Patients randomized to the control arm will receive the standard of care, according to (inter)national clinical practice guidelines. This will consist of (chemo)radiotherapy to the primary tumor with standard elective neck irradiation in all patients. No sentinel lymph node biopsy will be performed.
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Outcome Measures
Primary Outcome Measures
- Number of patients with regional recurrence [24 months]
Only regional recurrences in the absence of synchronous local recurrence or second primary tumors are considered as events
- Patiënt reported xerostomia related quality of life as assessed by EORTC Quality of Life Questionnaire Head and Neck Module (QLQ-H&N35) [6 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Newly diagnosed stage cT1-4N0M0 squamous cell carcinoma of the oropharynx, larynx or hypopharynx
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Adequate staging of the neck demonstrating stage cN0 (ultrasound with cytology, CT and/or MRI and PET)
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Recommendation for curative intent (chemo)radiotherapy made by a multidisciplinary head and neck oncology team.
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Elective neck irradiation is indicated according to current guidelines
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Patient is ≥18 years, fit for general anesthesia and provided written informed consent
Exclusion Criteria:
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Patients with recurrent disease and those who had (previous) anticancer treatment to the head and neck area
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Patients that qualify for proton therapy and want to be treated accordingly
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Any active invasive malignancy within the last 3 years
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Any psychological, physical or sociological condition potentially hampering compliance with the study protocol
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Netherlands Cancer Institute | Amsterdam | Netherlands | ||
| 2 | Leiden University Medical Center | Leiden | Netherlands | ||
| 3 | Maastricht University Medical Center | Maastricht | Netherlands | ||
| 4 | Radboud University Nijmegen Medical Center | Nijmegen | Netherlands | ||
| 5 | Erasmus Medical Center | Rotterdam | Netherlands | ||
| 6 | University Medical Center Utrecht | Utrecht | Netherlands |
Sponsors and Collaborators
- Radboud University Medical Center
- UMC Utrecht
- The Netherlands Cancer Institute
- Erasmus Medical Center
- Leiden University Medical Center
- Maastricht University Medical Center
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PRIMO