General

Guideline Title

ACR Appropriateness Criteria® retreatment of recurrent head and neck cancer after prior definitive radiation.

Bibliographic Source(s)

McDonald MW, Beitler JJ, Busse PM, Cooper JS, Koyfman S, Quon H, Ridge JA, Saba NF, Salama JK, Siddiqui F, Smith RV, Worden F, Yao M, Yom SS, Expert Panel on Radiation Oncology-Head & Neck Cancer. ACR Appropriateness Criteria® retreatment of recurrent head and neck cancer after prior definitive radiation [online publication]. Reston (VA): American College of Radiology (ACR); 2014. 12 p. [67 references]

Guideline Status

This is the current release of the guideline.

This guideline updates a previous version: McDonald MW, Lawson J, Beitler JJ, Garg MK, Quon H, Ridge JA, Saba N, Salama J, Smith RV, Yeung AR, Yom SS, Expert Panel on Radiation Oncology-Head & Neck Cancer. ACR Appropriateness Criteria® retreatment of recurrent head and neck cancer after prior definitive radiation. [online publication]. Reston (VA): American College of Radiology (ACR); 2010. 8 p. [52 references]

Recommendations

Major Recommendations

ACR Appropriateness Criteria®

Clinical Condition: Retreatment of Recurrent Head and Neck Cancer after Prior Definitive Radiation

Variant 1: 68-year-old man with T3N2bM0 pyriform sinus squamous cell carcinoma status post concurrent chemoradiation (70 Gy gross disease/54 Gy uninvolved neck plus 3 cycles of cisplatin 100 mg/m2 q 21 days). Post-treatment follow-up is sparse, and one year after treatment, his family brings him for evaluation because of pain and significant weight loss. He has bulky, biopsy-proven recurrent disease in the hypopharynx with extensive prevertebral fascia involvement on imaging, in addition to bilateral neck lymphadenopathy. There is no evidence of distant disease on restaging. KPS is 50 (requires considerable assistance and frequent care).

Treatment	Rating	Comments
Best supportive care/hospice	9
Chemotherapy (including biologic agents) alone	5
Reirradiation with palliative intent	5
Reirradiation alone to the recurrent disease (primary and necks) with curative intent	1
Reirradiation with chemotherapy with curative intent	1
Rating Scale : 1,2,3 Usually not appropriate; 4,5,6 May be appropriate; 7,8,9 Usually appropriate

Note: Abbreviations used in the tables are listed at the end of the “Major Recommendations” field.

Variant 2: 60-year-old man with T3N2aM0 supraglottic squamous cell carcinoma status post concurrent chemoradiation (70 Gy gross disease/54 Gy uninvolved neck plus 3 cycles of cisplatin 100 mg/m2 q 21 days). One year after treatment, he has biopsy-proven squamous cell carcinoma in the base of tongue, clinical T2, without evidence of distant or regional disease on restaging. Conservative resection at the base of tongue is performed with positive margins. There are no major complications in postoperative healing. KPS is 70 (cares for self, unable to carry on normal activity). Further surgical resection would require a total glossectomy, which the patient declines.

Treatment	Rating	Comments
Reirradiation (using preferred technique) with chemotherapy with curative intent	8
Reirradiation alone (using preferred technique) curative intent	5
Close observation	4
Chemotherapy (including biologic agents) alone	3
Reirradiation Technique
External beam radiation	6
Brachytherapy	6
Combined external beam and brachytherapy	6
Rating Scale : 1,2,3 Usually not appropriate; 4,5,6 May be appropriate; 7,8,9 Usually appropriate

Note: Abbreviations used in the tables are listed at the end of the “Major Recommendations” field.

Variant 3: 55-year-old man with pT4apN2bM0 glottic squamous cell carcinoma status post total laryngectomy and postoperative concurrent chemoradiation (60 Gy postoperative bed and bilateral neck plus 3 cycles of cisplatin 100 mg/m2 q 21 days). One year after treatment, he has a 4-cm level III mass in his initially involved neck, which is squamous cell carcinoma on fine-needle aspiration. There is no evidence of distant disease on restaging. An ipsilateral salvage neck dissection was performed. There was extracapsular extension at the nodal mass; 16 additional lymph nodes were negative. There are no major complications in postoperative healing. KPS is 70.

Treatment	Rating	Comments
Reirradiation (using preferred technique) with chemotherapy with curative intent	8
Close observation	5
Reirradiation alone (using preferred technique) curative intent	5
Chemotherapy (including biologic agents) alone	3
Reirradiation Technique
External beam radiation	8
Brachytherapy (assumes catheters placed at surgery)	8
External beam plus brachytherapy or intraoperative	8
Intraoperative radiation/p>	7
Rating Scale : 1,2,3 Usually not appropriate; 4,5,6 May be appropriate; 7,8,9 Usually appropriate

Note: Abbreviations used in the tables are listed at the end of the “Major Recommendations” field.

Variant 4: 53-year-old woman with T3N2 WHO grade 3 nasopharyngeal carcinoma treated 26 months ago with definitive chemoradiation (69.96 Gy to gross disease, 59.4 Gy elective volumes plus 3 cycles cisplatin 100 mg/m2 q 21 days and adjuvant cisplatin/5-FU) presents with imaging consistent with T2-recurrence extending into the parapharyngeal space, which is confirmed on endoscopy and biopsy. Examination and imaging find no evidence of regional or distant disease. She tolerated initial treatment well, has chronic xerostomia but no evidence of CNS late toxicities. She has a KPS of 80 (normal activity with effort, some symptoms).

Treatment	Rating	Comments
Reirradiation (using preferred technique) with chemotherapy with curative intent	7
Reirradiation alone (using preferred technique) curative intent	6
Chemotherapy (including biologic agents) alone	3
Nasopharyngectomy	3	This treatment may be more appropriate for smaller volume recurrence. Parapharyngeal extension is not generally amenable to complete surgical resection.
Best supportive care/hospice	1
Reirradiation Technique
External beam alone to dose ≥60 Gy	7
External beam plus stereotactic radiation boost	6
External beam plus brachytherapy boost	4	This treatment may be more appropriate for smaller volume recurrence. Intracavitary brachytherapy cannot adequately cover parapharyngeal extension.
Stereotactic radiation therapy alone	4
Brachytherapy alone	2	This treatment may be more appropriate for smaller volume recurrence. Intracavitary brachytherapy cannot adequately cover parapharyngeal extension.
Rating Scale : 1,2,3 Usually not appropriate; 4,5,6 May be appropriate; 7,8,9 Usually appropriate

Note: Abbreviations used in the tables are listed at the end of the “Major Recommendations” field.

Variant 5: 57-year-old woman with T2N2b squamous cell carcinoma treated with definitive chemoradiation (70 Gy gross disease/54 Gy uninvolved neck plus 3 cycles of cisplatin 100 mg/m2 q 21 days) is found to have recurrent, unresectable disease in the infratemporal fossa, eroding the clivus and extending to foramen ovale 6 months after treatment, which is biopsy-proven recurrent squamous cell carcinoma. Review of her prior treatment records shows that the recurrent disease is within an intermediate-dose region, which received approximately 50 Gy. She tolerated initial treatment well, has mild neck fibrosis and mild xerostomia, and has a KPS of 80. She consents to reirradiation with curative intent with concurrent chemotherapy.

Treatment	Rating	Comments
Volume
Reirradiation to recurrent tumor volume with limited margin (0.5-2 cm)	8
Reirradiation to recurrent tumor volume and limited elective nodal reirradiation	3
Technique
3-D CRT	3
IMRT	8
Proton therapy	6
SBRT	3	The large volume and proximity of the target to critical neural structures, in addition to the short interval from prior radiation, suggest that aggressively hypofractionated treatment is not as appropriate as fractionated therapy.
Dose to Recurrent Disease (if not SBRT)
Reirradiation <50 Gy	3
Reirradiation 50-59 Gy	4
Reirradiation 60 Gy or more	8
Fractionation (if not SBRT)
Once daily fractionation, 1.8-2 Gy, planned continuous course	8
Twice daily fractionation, 1.2 Gy, planned continuous course	7
Twice daily fractionation, 1.5 Gy, planned split course or weekly cycles	4
Once daily fractionation, 1.8-2 Gy, planned split course	1
Rating Scale : 1,2,3 Usually not appropriate; 4,5,6 May be appropriate; 7,8,9 Usually appropriate

Note: Abbreviations used in the tables are listed at the end of the “Major Recommendations” field.

Summary of Literature Review

Introduction/Background

Despite treatment intensification for patients with head and neck squamous cell carcinoma (HNSCC), including altered radiation fractionation and the addition of chemotherapy to radiation, physicians and patients still face the significant challenge of recurrent or second tumors arising within or in close proximity to previously irradiated tissues. At 5 years after therapy, locoregional recurrences develop in 16% to 25% of patients treated with definitive chemoradiation for larynx preservation or with postoperative chemoradiation for high-risk HNSCC and 17% to 52% of patients treated with definitive chemoradiation for locally advanced unresectable disease. Locally recurrent tumors may arise from residual neoplastic cells that survive initial treatment, perhaps because of biological parameters and tumor molecular profiles associated with radiosensitivity. Insufficiencies in initial radiation treatment parameters such as radiation dose, volume, fractionation, and treatment duration, were noted in a high percentage of patients enrolled on a small phase I trial of reirradiation and are other potential sources of recurrence. Second cancers may arise from underlying field cancerization, as a radiation-induced malignancy, or as a de novo process. A second HNSCC arising in the vicinity of the prior tumor may be indistinguishable from a local recurrence of the primary tumor. Approximately 15% of patients have developed a second primary cancer within 5 years of radiation alone for HNSCC, and approximately one-quarter of these are in the head and neck.

Rationale for Retreatment

Because locoregional tumor progression is the predominant cause of death in patients with head and neck cancer, achieving local control in patients with recurrent disease may impact survival. Indeed, results of a randomized trial in patients with recurrent HNSCC undergoing macroscopic complete salvage surgery found improved local control and disease-free survival in those receiving postoperative reirradiation with chemotherapy compared with observation. In that trial, retrospective analysis of a single institution experience found improved overall survival when local tumor control was achieved in patients reirradiated for recurrent head and neck cancer.

In patients with recurrent or second primary tumors of the head and neck, local tumor growth is a potential source of great morbidity to include pain, disfigurement, bleeding, infection, and alteration of speech and swallowing. In a report of 150 patients reirradiated for head and neck cancer using stereotactic body radiotherapy (SBRT) with or without cetuximab, patient-reported quality of life, after an initial 1-month decline following reirradiation, noted progressive improvements in swallowing, speech, saliva, activity, and recreation, underlining the importance of local tumor control on patient quality of life.

Patient Evaluation and Selection for Retreatment

Patients presenting with recurrent or second primary tumors should undergo careful restaging evaluation prior to committing the patient to aggressive therapy with curative intent, be it surgery or reirradiation. In addition to the use of computed tomography (CT) or magnetic resonance imaging (MRI) to evaluate the extent of the recurrent tumor, positron emission tomography (PET)/CT or, at a minimum, chest CT, should be strongly considered to evaluate for metastatic disease. In addition to documenting the extent of recurrent disease, the evaluation should include an assessment of the patient’s comorbidities and life expectancy, performance status, speech and swallowing function, nutritional status, severity of current symptoms, expectations of retreatment, and documentation of sequelae of prior treatment, such as fibrosis, carotid stenosis, dysphagia, xerostomia, or osteoradionecrosis. Patients with metastatic disease, poor performance status, or severe toxicity from prior radiation are typically poor candidates for reirradiation. In addition to careful patient selection, the panel strongly recommends evaluation and treatment at care centers with an experienced head and neck oncology team equipped with the resources and experience to manage the complexities and toxicities of retreatment. (See Variant 1 above).

Resectable Disease Recurrence

For patients with operable disease recurrence, surgical resection is considered the standard of care and may provide long-term disease control in 25% to 45% of patients, and upwards of 80% in patients with small recurrent laryngeal tumors. In multivariate analysis of pooled data from 9 phase I and II trials of reirradiation with chemotherapy for recurrent head and neck cancer, salvage surgical resection or debulking was associated with a lower hazard ratio (HR) for death (HR 0.52, P =.0006). In contrast, multivariate analysis of a large single institution experience found no statistically significant association between survival and salvage surgery, although increasing size of residual tumor after salvage surgery was associated with an increased risk of death (HR 1.12 per cm, P <.0001). These disparate findings likely highlight the inability of retrospective analyses to fully account for patient selection in therapeutic decision-making.

However, even patients who undergo complete resection of recurrent disease with uninvolved margins have a risk of local failure as high as 59%. Single-institution series have demonstrated the feasibility and efficacy of postoperative reirradiation alone or with concurrent chemotherapy in patients at significant risk of further local recurrence, including those with gross residual disease, positive margins, or extracapsular extension. A phase III multicenter trial conducted by the Groupe d’Etude des Tumeurs de la Tête et du Cou and the Groupe d’Oncologie et de Radiothérapie Tête et Cou randomized the care of patients with recurrent HNSCC in previously irradiated tissue after macroscopic complete surgical resection to observation or reirradiation with chemotherapy. Both local control and disease-free survival (the primary endpoint) were improved in patients receiving postoperative reirradiation and chemotherapy, with an HR of 1.68, although there was no apparent difference in overall survival compared with those observed after surgery. Grade 3 or 4 acute toxicity was seen in 28% of those reirradiated, and at 2 years, grade 3 or 4 toxicity was as high as 40%, compared with 10% in those randomized to postoperative observation. Nearly half of the patients randomized to observation had a subsequent local recurrence and half of those received salvage reirradiation with chemotherapy. (See Variant 2 above).

Unresectable Disease Recurrence

Significant proportions of patients with recurrent disease have tumors that are technically unresectable, or the patients are medically unfit for surgery or refuse radical surgery. In these patients, palliative chemotherapy has been considered the standard of care. Multiagent chemotherapy regimens may have a response rate near 35%, but results are rarely durable and long-term survival is rare. Incorporation of newer biological agents may improve outcomes. Results from the phase III multicenter EXTREME trial in patients with recurrent or metastatic HNSCC found that the addition of cetuximab to platinum and fluorouracil chemotherapy improved median survival to 10.1 months compared with 7.4 months for those receiving platinum-fluorouracil alone. All patients included in the trial had been deemed ineligible for further local therapy with surgery or radiation, and approximately half of the patients had only locoregional disease without evidence of distant metastatic spread.

For patients with unresectable disease, reirradiation is the only potentially curative treatment. The Radiation Therapy Oncology Group® (RTOG®) has completed 2 phase II studies using reirradiation and chemotherapy in this population. RTOG® 96-10 used concurrent hydroxyurea and 5-fluorouracil and achieved a median survival of 8.5 months and a 2-year survival rate of 15.2%, whereas RTOG® 99-11 employed concurrent cisplatin and paclitaxel, with a median survival of 12.1 months and a 2-year survival rate of 25.9%. A 5-year overall survival estimate of 14.3% was reported from pooled analysis of 9 prospective trials from a single institution, suggesting that reirradiation with chemotherapy is potentially curative in a small proportion of patients. Acute toxicity in both RTOG studies was high. In RTOG® 99-11, nearly half developed grade 3 toxicity, 23% grade 4, and an additional 5%, grade 5 toxicity (death). Although these 2-year survival outcomes appear superior to series of patients treated with chemotherapy alone, whether this apparent improvement is the result of selection bias is uncertain. A phase III trial randomizing patients with locally recurrent previously irradiated HNSCC to reirradiation with chemotherapy or chemotherapy alone was opened by the RTOG® but closed secondary to poor accrual.

Nodal Disease Relapse

The prognosis for patients with recurrent neck disease after previous nodal irradiation is poor. However, patients with cervical lymph node recurrence, alone or in combination with primary site recurrence, were included in the RTOG® phase II studies, in institutional series of reirradiation, and in the randomized trial of reirradiation with chemotherapy following macroscopic complete resection. Initial experience with CT-guided interstitial high-dose rate brachytherapy in a retrospective report of highly selected patients also reported favorable rates of local control and survival outcomes comparable to the RTOG® trials of reirradiation and chemotherapy. The Eastern Cooperative Oncology Group (ECOG) has an ongoing clinical trial (ECOG 1311) for patients at 6 to 16 weeks after completion of chemoradiation therapy for HNSCC and who undergo salvage neck dissection for persistent nodal disease. In ECOG 1311, patients are randomized to afatinib or placebo. (See Variant 3 above.)

Nasopharynx

Local failure, with or without recurrent nodal disease, may develop in 8% to 10% of patients treated with chemoradiation for nasopharyngeal carcinoma. A large, retrospective analysis suggests patients undergoing reirradiation or nasopharyngectomy for recurrent disease have improved overall survival compared with those who receive chemotherapy alone or no salvage treatment, although selection bias exists, and in one series, the benefit appeared confined to patients with T1-T2 recurrence. Patients with local-only recurrence have shown improved outcomes compared to those with local and nodal recurrence. Experience with nasopharyngeal retreatment has included combinations of nasopharyngectomy, chemotherapy, external beam radiation therapy (EBRT), brachytherapy, intraoperative radiotherapy, hyperthermia, stereotactic radiosurgery, hypofractionated stereotactic radiotherapy (FSRT), and proton therapy. Across these modalities, mortality with retreatment is <5%. Advances in skull-base surgery have increased the feasibility of salvage nasopharyngectomy. Long-term local control after salvage nasopharyngectomy has been reported in 58% of patients with recurrent T1 disease, and 28% in patients with recurrent T2 disease, with approximately 40% of patients receiving postoperative reirradiation as well, usually for positive margins. Superior results were seen in a series of patients in whom endoscopic en-bloc resections were achieved. Brachytherapy alone appears to be very successful in salvaging limited-volume recurrent disease (recurrent T1 or minimal T2) with long-term local control approaching 90%.

A small, institutional study of reirradiation with chemotherapy for recurrent T1–T4 nasopharynx disease found no difference in local control or survival for patients treated with EBRT or those treated with combined EBRT and brachytherapy, but grade 3 or worse late toxicity was 8% when treatment incorporated brachytherapy versus 73% with EBRT alone, although there were more advanced recurrent T-stage patients among those treated with EBRT alone. Multivariate analysis in a larger series found that only the recurrent T stage predicted central nervous system complications. When EBRT alone is used, disease control appears superior when reirradiation doses of ≥60 Gy are employed. In addition to the published experience with intensity-modulated radiation therapy (IMRT) for primary treatment of nasopharyngeal carcinoma, this technique has demonstrated its feasibility for retreatment of locally recurrent disease as well. FSRT outcomes have been reported in small institutional series. Three to 5-year local failure-free survival rates of 75% to 79% have been reported, with crude rates of serious toxicity reported at 16% to 25%, including nasopharyngeal necrosis and hemorrhage. (See Variant 4 above.)

Radiation Volume, Fractionation, Dose, and Constraints

Patients with recurrent HNSCC following prior radiation are a heterogeneous group. Differences in the location and extent of recurrent tumor, initial radiation treatment parameters, elapsed time since prior treatment, extent of normal tissue sequelae, and relatively sparse data on acute and late normal tissue recovery from prior treatment and tolerance to reirradiation pose a significant challenge to the formulation of widely applicable schemata for reirradiation.

The optimal treatment volume for reirradiation is uncertain. The RTOG phase II studies of reirradiation with chemotherapy targeted a volume created from a 2-cm expansion around the recurrent gross tumor volume. In an effort to limit the toxicity of retreatment, many reported experiences with reirradiation have targeted the recurrent gross disease with limited margin and not added elective nodal reirradiation. In a series of patients undergoing salvage surgery for local recurrence after initially irradiated clinically node-negative HNSCC, 29 of 30 patients undergoing elective node dissection were free of lymph node metastases, suggesting that lymphatic spread to a previously irradiated neck is uncommon. In patients who presented with initial neck disease or who have larger, inoperable local recurrences, the risk of recurrent nodal disease is unclear. Pattern of failure analysis in a series of 66 patients with unresectable recurrent HNSCC reirradiated with curative intent using a 0.5-cm margin around recurrent gross disease found that 45 of 47 patients (96%) who suffered a second local failure experienced recurrence within the retreatment volume. Other patterns of failure analysis also suggest that limited reirradiation volumes that omit elective reirradiation of nodal areas are sufficient.

In terms of the dose delivered in the second treatment course, institutional data suggest a greater likelihood of local control with administration of at least 50 to 60 Gy in reirradiation. Both RTOG® phase II studies used an accelerated hyperfractionated regimen delivering 1.5 Gy twice daily in 4 week-on/week-off cycles to a total dose of 60 Gy, as previously developed at the University of Chicago. Although this regimen appears to facilitate intensification of concurrent chemotherapy, it prolongs overall treatment time by introducing multiple planned radiation treatment breaks, which are necessary to manage toxicity but may be radiobiologically deleterious to local control. In a phase I trial, researchers at the University of Alabama were able to eliminate planned treatment breaks and deliver continuous course radiation with a delayed concomitant boost after making some dose reductions in concurrent 5-fluorouracil and hydroxyurea. Multiple single-institution reports of reirradiation have used once daily standard fractionation in a planned continuous treatment course with acute treatment-related deaths of 0% to 1% compared with the 5% to 10% rate of acute grade 5 toxicity reported in studies using the accelerated hyperfractionated weekly cycle regimen. Differences in study design, patient selection, and chemotherapy regimens make it difficult to discern what independent effect, if any, differences in radiation fractionation may have on the risk of acute grade 5 toxicity.

In an effort to improve dose conformality and minimize reirradiation of non-target tissues, many recently published institutional series of reirradiation have utilized IMRT. In one retrospective series, reirradiation with IMRT was associated with improved local control compared to conventional radiation techniques. This apparent improvement may stem from advantages in dose distribution with potentially better coverage of retreatment targets in close proximity to previously irradiated critical normal structures but may also reflect unmeasured biases such as improvements in patient staging, imaging, and increasing expertise with reirradiation. Proton therapy, a radiation modality with a finite range and no exit dose, has also been reported in reirradiation of nasopharyngeal cancer. In light of the risk of significant toxicity to normal tissues with reirradiation, highly conformal techniques that limit the volume of reirradiation are preferred.

SBRT is a highly conformal, precisely targeted radiation technique that delivers a high dose of radiation to a limited volume in 1 to 5 fractions. An early institutional retrospective report of SBRT in primary, recurrent, or metastatic HNSCC reported a 1-year tumor control rate of 60% for those with recurrent tumors and a median survival of 7 months. There was no apparent difference in results between those treated with one or 2–5 fractions. In a phase I dose-escalation trial of SBRT in reirradiation of head and neck cancer, a dose of 44 Gy in 5 fractions was delivered without reaching acute dose-limiting toxicity. An institutional experience of 85 patients receiving SBRT (median 35 Gy in 5 fractions) for recurrent, previously irradiated head and neck cancer reported a 2-year local control of 31%, median overall survival of 11.5 months, and no grade 4 or 5 treatment-related toxicities. Treatment to doses of 35 to 44 Gy in 5 fractions was associated with improved local control compared to those receiving total doses <35 Gy in 5 fractions, with no discernible increase in acute or late toxicity. In contrast, another institutional series reported a carotid blowout rate of 17% after reirradiation with SBRT (median 30 Gy in 5 fractions). A retrospective matched cohort study of SBRT (median 40 Gy in 5 fractions) with or without cetuximab suggests that the addition of concurrent cetuximab to SBRT improves both local control (49% at 2 years) and overall survival (53% at 2 years) compared to SBRT alone.

Normal tissue tolerances to reirradiation are poorly defined, and there are numerous potential contributing factors including patient comorbidities, interval from prior therapy, and the effect of partial volume dose. There are scant data to guide expectations on risks or formulate dose constraints for soft tissues, bone, and neurovascular structures after reirradiation, especially with the large-dose fractions given with SBRT. Given the poor survival in patients with recurrent HNSCC, many patients may not survive long enough to see potential late normal tissue complications from reirradiation. Carotid blowout is an uncommon but usually fatal complication of salvage therapy that may occur in approximately 3% of patients receiving reirradiation based on a review of published series. Spinal cord myelopathy is particularly feared as portions of the cervical spinal cord have typically already received 45 to 50 Gy, the conventional recommended tolerance dose, from the initial radiation treatment. Animal experiments in rhesus monkeys suggest substantial recovery of the cervical and upper thoracic spinal cord from initial radiation after just one year, with a low risk of myelopathy after reirradiation despite cumulative doses >100 Gy. Human data include the apparent tolerance of full-dose reirradiation in children with recurrent intracranial ependymoma suggesting that significant spinal cord and brainstem recovery occur. Additional clinical data suggest that the risk of spinal cord myelopathy is rare when the interval between radiation courses is at least 6 months and when the cumulative biologically effective dose to the spinal cord (assuming an alpha/beta ratio of 2) is kept below 135.5 Gy. The RTOG® phase II studies of reirradiation and several institutional experiences limited the cumulative spinal cord dose to 50 Gy; others to 60 Gy, and others have allowed for normal tissue recovery of up to 50% of prior dose and delivered somewhat higher cumulative spinal cord doses, all with a reported risk of myelopathy of <1%. (See Variant 5 above.)

Summary

As in the management of initial disease, multidisciplinary evaluation and treatment of patients with recurrent or second primary head and neck cancer is critical.
Surgical salvage is considered the standard of care for patients with technically resectable disease who are medically fit for surgery. Randomized data support the role of postoperative reirradiation with chemotherapy to improve local control and disease-free survival.
Patient selection for reirradiation is critical. Additional data are needed to determine which patient subsets will most likely benefit from reirradiation. Patients with metastatic disease, poor performance status, or severe toxicity from prior radiation are typically poor candidates for reirradiation.
For patients treated with curative intent, reirradiation with chemotherapy (including biologic agents) is preferred over reirradiation alone.
For patients treated with curative intent, reirradiation to doses of 60 Gy or greater to the recurrent disease are recommended, and elective nodal reirradiation does not appear to be warranted. Conventional fractionation or hyperfractionation with a minimum 6-hour interval are favored.
Highly conformal radiation techniques such as IMRT are recommended over less conformal modalities.
Newer conformal radiation modalities, including stereotactic body radiation therapy and proton therapy, may be appropriate in select cases. Additional data are needed to determine which patient subsets will most likely benefit from these modalities.

Abbreviations

3-D CRT, 3-dimensional conformal radiation therapy
5-FU, 5-fluorouracil
CNS, central nervous system
IMRT, intensity-modulated radiation therapy
KPS, Karnofsky Performance Status
SBRT, stereotactic body radiotherapy
TNM, tumor, node, metastasis
WHO, World Health Organization

Clinical Algorithm(s)

Algorithms were not developed from criteria guidelines.

Scope

Disease/Condition(s)

Recurrent head and neck cancer

Guideline Category

Treatment

Clinical Specialty

Oncology
Otolaryngology
Radiation Oncology
Surgery

Intended Users

Health Plans
Hospitals
Managed Care Organizations
Physicians
Utilization Management

Guideline Objective(s)

To evaluate the appropriateness of retreatment procedures for patients with recurrent head and neck cancer after prior definitive radiation

Target Population

Patients with recurrent head and neck cancer after prior definitive radiation

Interventions and Practices Considered

Reirradiation * Alone to the recurrent disease (primary and necks) with curative intent * With palliative intent * With chemotherapy with curative intent * To recurrent tumor volume, with limited margin * To recurrent tumor volume and limited elective nodal reirradiation * Doses and fractionation
Chemotherapy (including biologic agents) alone
Close observation
Nasopharyngectomy
Best supportive care/hospice
Reirradiation technique * External beam radiation * Brachytherapy alone * Combined external beam and brachytherapy boost * Intraoperative radiation * External beam plus brachytherapy boost or intraoperative * External beam plus stereotactic irradiation boost * Stereotactic radiation therapy alone * 3-dimensional conformal radiation therapy (3-D CRT) * Intensity-modulated radiotherapy (IMRT)

Major Outcomes Considered

Local tumor control
Disease-free survival
Overall survival
Median survival time
Treatment-related morbidity and mortality

Methodology

Methods Used to Collect/Select the Evidence

Searches of Electronic Databases

Description of Methods Used to Collect/Select the Evidence

Literature Search Procedure

Staff search in PubMed only for peer reviewed medical literature for routine searches. Any article or guideline may be used by the author in the narrative but those materials may have been identified outside of the routine literature search process.

The Medline literature search is based on keywords provided by the topic author. The two general classes of keywords are those related to the condition (e.g., ankle pain, fever) and those that describe the diagnostic or therapeutic intervention of interest (e.g., mammography, MRI).

The search terms and parameters are manipulated to produce the most relevant, current evidence to address the American College of Radiology Appropriateness Criteria (ACR AC) topic being reviewed or developed. Combining the clinical conditions and diagnostic modalities or therapeutic procedures narrows the search to be relevant to the topic. Exploding the term “diagnostic imaging” captures relevant results for diagnostic topics.

The following criteria/limits are used in the searches.

Articles that have abstracts available and are concerned with humans.
Restrict the search to the year prior to the last topic update or in some cases the author of the topic may specify which year range to use in the search. For new topics, the year range is restricted to the last 10 years unless the topic author provides other instructions.
May restrict the search to Adults only or Pediatrics only.
Articles consisting of only summaries or case reports are often excluded from final results.

The search strategy may be revised to improve the output as needed.

Number of Source Documents

The total number of source documents identified as the result of the literature search is not known.

Methods Used to Assess the Quality and Strength of the Evidence

Weighting According to a Rating Scheme (Scheme Given)

Rating Scheme for the Strength of the Evidence

Study Quality Category Definitions

Category 1 - The study is well-designed and accounts for common biases.

Category 2 - The study is moderately well-designed and accounts for most common biases.

Category 3 - There are important study design limitations.

Category 4 - The study is not useful as primary evidence. The article may not be a clinical study or the study design is invalid, or conclusions are based on expert consensus. For example:

The study does not meet the criteria for or is not a hypothesis-based clinical study (e.g., a book chapter or case report or case series description).
The study may synthesize and draw conclusions about several studies such as a literature review article or book chapter but is not primary evidence.
The study is an expert opinion or consensus document.

Methods Used to Analyze the Evidence

Systematic Review with Evidence Tables

Description of the Methods Used to Analyze the Evidence

The topic author drafts or revises the narrative text summarizing the evidence found in the literature. American College of Radiology (ACR) staff draft an evidence table based on the analysis of the selected literature. These tables rate the strength of the evidence (study quality) for each article included in the narrative text.

The expert panel reviews the narrative text, evidence table, and the supporting literature for each of the topic-variant combinations and assigns an appropriateness rating for each procedure listed in the table. Each individual panel member assigns a rating based on his/her interpretation of the available evidence.

More information about the evidence table development process can be found in the ACR Appropriateness Criteria® Evidence Table Development document (see the “Availability of Companion Documents” field).

Methods Used to Formulate the Recommendations

Expert Consensus (Delphi)

Description of Methods Used to Formulate the Recommendations

Rating Appropriateness

The appropriateness ratings for each of the procedures included in the Appropriateness Criteria topics are determined using a modified Delphi methodology. A series of surveys are conducted to elicit each panelist’s expert interpretation of the evidence, based on the available data, regarding the appropriateness of an imaging or therapeutic procedure for a specific clinical scenario. American College of Radiology (ACR) staff distribute surveys to the panelists along with the evidence table and narrative. Each panelist interprets the available evidence and rates each procedure. The surveys are completed by panelists without consulting other panelists. The appropriateness rating scale is an ordinal scale that uses integers from 1 to 9 grouped into three categories: 1, 2, or 3 are in the category “usually not appropriate”; 4, 5, or 6 are in the category “may be appropriate”; and 7, 8, or 9 are in the category “usually appropriate.” Each panel member assigns one rating for each procedure for a clinical scenario. The ratings assigned by each panel member are presented in a table displaying the frequency distribution of the ratings without identifying which members provided any particular rating.

If consensus is reached, the median rating is assigned as the panel’s final recommendation/rating. Consensus is defined as eighty percent (80%) agreement within a rating category. A maximum of three rounds may be conducted to reach consensus. Consensus among the panel members must be achieved to determine the final rating for each procedure.

If consensus is not reached, the panel is convened by conference call. The strengths and weaknesses of each imaging procedure that has not reached consensus are discussed and a final rating is proposed. If the panelists on the call agree, the rating is proposed as the panel’s consensus. The document is circulated to all the panelists to make the final determination. If consensus cannot be reached on the call or when the document is circulated, “No consensus” appears in the rating column and the reasons for this decision are added to the comment sections.

This modified Delphi method enables each panelist to express individual interpretations of the evidence and his or her expert opinion without excessive influence from fellow panelists in a simple, standardized and economical process. A more detailed explanation of the complete process can be found in additional methodology documents found on the ACR Web site (see also the “Availability of Companion Documents” field).

Rating Scheme for the Strength of the Recommendations

Not applicable

Cost Analysis

A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation

Internal Peer Review

Description of Method of Guideline Validation

Criteria developed by the Expert Panels are reviewed by the American College of Radiology (ACR) Committee on Appropriateness Criteria.

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The recommendations are based on analysis of the current literature and expert panel consensus.

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Selection of appropriate retreatment procedures for patients with recurrent head and neck cancer after prior definitive radiation

Potential Harms

Acute and late toxicities of radiotherapy retreatment, including death (see the “Major Recommendations” field for details)

Qualifying Statements

The American College of Radiology (ACR) Committee on Appropriateness Criteria and its expert panels have developed criteria for determining appropriate imaging examinations for diagnosis and treatment of specified medical condition(s). These criteria are intended to guide radiologists, radiation oncologists, and referring physicians in making decisions regarding radiologic imaging and treatment. Generally, the complexity and severity of a patient’s clinical condition should dictate the selection of appropriate imaging procedures or treatments. Only those examinations generally used for evaluation of the patient’s condition are ranked. Other imaging studies necessary to evaluate other co-existent diseases or other medical consequences of this condition are not considered in this document. The availability of equipment or personnel may influence the selection of appropriate imaging procedures or treatments. Imaging techniques classified as investigational by the U.S. Food and Drug Administration (FDA) have not been considered in developing these criteria; however, study of new equipment and applications should be encouraged. The ultimate decision regarding the appropriateness of any specific radiologic examination or treatment must be made by the referring physician and radiologist in light of all the circumstances presented in an individual examination.

Implementation of the Guideline

Description of Implementation Strategy

An implementation strategy was not provided.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need

End of Life Care
Getting Better
Living with Illness

IOM Domain

Effectiveness

Identifying Information and Availability

Bibliographic Source(s)

McDonald MW, Beitler JJ, Busse PM, Cooper JS, Koyfman S, Quon H, Ridge JA, Saba NF, Salama JK, Siddiqui F, Smith RV, Worden F, Yao M, Yom SS, Expert Panel on Radiation Oncology-Head & Neck Cancer. ACR Appropriateness Criteria® retreatment of recurrent head and neck cancer after prior definitive radiation [online publication]. Reston (VA): American College of Radiology (ACR); 2014. 12 p. [67 references]

Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released

2010 (revised 2014)

Guideline Developer(s)

American College of Radiology - Medical Specialty Society

Source(s) of Funding

The American College of Radiology (ACR) provided the funding and the resources for these ACR Appropriateness Criteria®.

Guideline Committee

Committee on Appropriateness Criteria, Expert Panel on Radiation Oncology–Head & Neck Cancer

Composition of Group That Authored the Guideline

Panel Members : Mark W. McDonald, MD ( Principal Author ); Jonathan J. Beitler, MD, MBA; Paul M. Busse, MD, PhD; Jay S. Cooper, MD; Shlomo Koyfman, MD; Harry Quon, MD, MS; John A. Ridge, MD, PhD; Nabil F. Saba, MD; Joseph K. Salama, MD; Farzan Siddiqui, MD, PhD; Richard V. Smith, MD; Francis Worden, MD; Min Yao, MD, PhD; Sue S. Yom, MD, PhD ( Panel Chair )

Financial Disclosures/Conflicts of Interest

Not stated

Guideline Status

This is the current release of the guideline.

Guideline Availability

Available from the American College of Radiology (ACR) Web site.

Availability of Companion Documents

The following are available:

ACR Appropriateness Criteria®. Overview. Reston (VA): American College of Radiology; 2013 Nov. 3 p. Available from the American College of Radiology (ACR) Web site.
ACR Appropriateness Criteria®. Literature search process. Reston (VA): American College of Radiology; 2013 Apr. 1 p. Available from the ACR Web site.
ACR Appropriateness Criteria®. Evidence table development. Reston (VA): American College of Radiology; 2015 Nov. 5 p. Available from the ACR Web site.
ACR Appropriateness Criteria® retreatment of recurrent head and neck cancer after prior definitive radiation. Evidence table. Reston (VA): American College of Radiology; 2014. 23 p. Available from the ACR Web site.

Patient Resources

None available

NGC Status

This NGC summary was completed by ECRI Institute on December 22, 2010. This NGC summary was updated by ECRI Institute on August 27, 2014.

Copyright Statement

Instructions for downloading, use, and reproduction of the American College of Radiology (ACR) Appropriateness Criteria® may be found on the ACR Web site.

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