头颈部癌症放疗复发后的再次治疗 【美国2010ACR】

Date of origin: 2010 ACR Appropriateness Criteria® 1 Retreatment Head & Neck after Prior Definitive Radiation American College of Radiology ACR Appropriateness Criteria® RETREATMENT OF RECURRENT HEAD AND NECK CANCER AFTER PRIOR DEFINITIVE RADIATION Expert Panel on Radiation Oncology–Head & Neck Cancer: Mark W. McDonald, MD1; Joshua Lawson, MD2; Jonathan J. Beitler, MD3; Madhur Kumar Garg, MD4; Harry Quon, MD, MS5; John A. Ridge, MD, PhD6; Nabil Saba, MD7; Joseph Salama, MD8; Richard V. Smith, MD9; Anamaria Reyna Yeung, MD10; Sue S. Yom, MD.11 Summary of Literature Review 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. Locoregional recurrences develop in 18%-20% of patients treated with definitive chemoradiation for larynx preservation [1] or with postoperative chemoradiation for high risk HNSCC [2-3] and 17%-33% of patients treated with definitive chemoradiation for locally advanced unresectable disease [4-5]. Locally recurrent tumors may arise from residual neoplastic cells that survive initial treatment, perhaps because of biological parameters that confer radio resistance [6] or insufficiencies in initial treatment parameters such as radiation dose, volume, fractionation, and treatment duration. Second cancers may arise from underlying field cancerization [7], 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 [8]. In the experience of the Radiation Therapy Oncology Group® (RTOG®), the rate of second head and neck primary tumors was 1% per year in patients previously treated with radiation alone for HNSCC [9]. 1Principal Author, Indiana University School of Medicine, Indianapolis, Indiana. 2Co-Author, University of California San Diego, La Jolla, California. 3Panel Chair, Emory University School of Medicine, Atlanta, Georgia. 4Montefiore Medical Center, Bronx, New York. 5University of Pennsylvania, Philadelphia, Pennsylvania. 6Fox Chase Cancer Center, Philadelphia, Pennsylvania, American College of Surgeons. 7Emory University, Atlanta, Georgia, American Society of Clinical Oncology. 8University of Chicago, Chicago, Illinois. 9Montefiore Medical Center, Bronx, New York, American College of Surgeons. 10University of Florida, Gainesville, Florida. 11University of California San Francisco, San Francisco, California. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through society representation on expert panels. Participation by representatives from collaborating societies on the expert panel does not necessarily imply society endorsement of the final document. Reprint requests to: Department of Quality & Safety, American College of Radiology, 1891 Preston White Drive, Reston, VA 20191-4397. Rationale for Retreatment In patients with recurrent or second primary tumors of the head and neck, local tumor growth is a potential source of great morbidity, with pain, disfigurement, bleeding, infection, and alteration of speech and swallowing. Because locoregional tumor progression is the predominant cause of death in patients with head and neck cancer [10], 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 [11], and 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 [12]. 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 radical salvage surgery or aggressive reirradiation. In addition to a computed tomography (CT) or magnetic resonance imaging (MRI) scan to evaluate the extent of the recurrent tumor, a positron emission tomography (PET)/CT should be strongly considered to evaluate for metastatic disease, or, at a minimum, a CT of the chest. In addition to documenting the extent of recurrent disease, the history and physical should include an assessment of patient’s comorbidities and life expectancy, performance status, speech and swallowing function, nutritional status, severity of current symptoms, expectations, 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 have typically been excluded from reported experiences with reirradiation. In addition to careful patient selection, the panel strongly recommends evaluation and treatment at tertiary-care centers with a head and neck oncology team equipped with the resources and experience to manage the complexities and toxicities of retreatment. ACR Appropriateness Criteria® 2 Retreatment Head & Neck after Prior Definitive Radiation Variant 1: 68-year-old male with T3N2bM0 pyriform sinus squamous cell carcinoma status post concurrent chemoradiation (70 Gy gross disease/54 Gy uninvolved neck + three cycles of cisplatin 100mg/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 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%-45% of patients [13-14], and upwards of 80% in patients with small recurrent laryngeal tumors [15]. However, even patients who undergo complete resection of recurrent disease with negative margins have a risk of local failure as high as 59% [16]. Single-institution series have demonstrated the feasibility and efficacy of postoperative reirradiation alone [17] or with concurrent chemotherapy [18] 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 patients with recurrent HNSCC in previously irradiated tissue post macroscopic complete surgical resection to observation or reirradiation with chemotherapy [11]. Both local control and disease-free survival (the primary endpoint) were improved in patients receiving postoperative reirradiation and chemotherapy, with a hazard ratio 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 two 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. ACR Appropriateness Criteria® 3 Retreatment Head & Neck after Prior Definitive Radiation Variant 2: 60-year-old male with T3N2aM0 supraglottic squamous cell carcinoma status post concurrent chemoradiation (70 Gy gross disease/54 Gy uninvolved neck + three cycles of cisplatin 100mg/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 Unresectable Disease Recurrence A significant proportion of patients with recurrent disease are technically unresectable, medically unfit for surgery, or refuse radical surgery [19]. 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 [20]. Incorporation of newer biological agents may improve outcomes [21]. Results from the phase III multicenter EXTREME trial in patients with recurrent or metastatic HNSCC found that the addition of cetuximab to platinum-based chemotherapy improved median survival to 10.1 months compared with 7.4 months for those receiving chemotherapy without cetuximab [22]. 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 RTOG® has completed two phase II studies using reirradiation and chemotherapy in this population. RTOG® 96-10 [23] used concurrent hydroxyurea and 5-fluorouracil and achieved a median survival of 8.5 months and a 2-year survival rate of 15.2%, while RTOG® 99-11 [24] employed concurrent cisplatin and paclitaxel, with a median survival of 12.1 months and a 2-year survival rate of 25.9%. Acute toxicity in both studies was high. In RTOG® 99-11, nearly half developed grade 3 toxicity, 23% grade 4, and an additional 5%, grade 5 toxicity (death). While these two- 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 notoriously poor [19,25]. However, patients with cervical lymph node recurrence, alone or in combination with primary site recurrence, were included in the RTOG® phase II studies [23-24], in institutional series of reirradiation [26-27], and in the randomized trial of reirradiation with chemotherapy following macroscopic complete resection [11]. Initial experience with CT-guided interstitial high-dose rate brachytherapy also reported favorable rates of local control and survival outcomes comparable to the RTOG® trials of reirradiation and chemotherapy [28]. ACR Appropriateness Criteria® 4 Retreatment Head & Neck after Prior Definitive Radiation Variant 3: 55-year-old male with pT4apN2bM0 glottic squamous cell carcinoma status post total laryngectomy and postoperative concurrent chemoradiation (60 Gy postoperative bed and bilateral neck + three cycles of cisplatin 100mg/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 7 Rating Scale: 1,2,3 Usually not appropriate; 4,5,6 May be appropriate; 7,8,9 Usually appropriate Nasopharynx Local failure, with or without recurrent nodal disease, may develop in 8%-10% of patients treated with chemoradiation for nasopharyngeal carcinoma [29-30]. 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 [31]. Patients with local-only recurrence have improved outcomes compared with those with local and nodal recurrence [32]. Experience with nasopharyngeal retreatment has included combinations of nasopharyngectomy, chemotherapy, external beam radiation therapy (EBRT), brachytherapy, intraoperative radiotherapy, hyperthermia, radiosurgery, and proton therapy [33]. Across these modalities, mortality with retreatment is <5% [31]. 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 [33]. Superior results were seen in a series of patients in whom endoscopic en-bloc resections were achieved [34]. 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% [35]. 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 [36]. Multivariate analysis in a larger series found that only the recurrent T stage predicted central nervous system complications [37]. When EBRT alone is used, disease control appears superior when reirradiation doses of ≥60 Gy are employed [32,37-38]. In addition to the published experience with IMRT for primary treatment of nasopharyngeal carcinoma, this technique has been demonstrated feasible for retreatment of locally recurrent disease as well [12,39- 40]. ACR Appropriateness Criteria® 5 Retreatment Head & Neck after Prior Definitive Radiation Variant 4: 53-year-old female 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 three cycles cisplatin 100mg/m2 q 21 days and adjuvant cisplatin/5FU) 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, and 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 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 May be more appropriate for smaller volume recurrence. Intracavitary brachytherapy cannot adequately cover parapharyngeal extension. Stereotactic radiation therapy alone 4 Brachytherapy alone 2 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 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 [41] pose a significant challenge to the formulation of widely applicable schemata for reirradiation. The optimal treatment volume for reirradiation is uncertain. 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 [42]. 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 [43]. 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 50-60 Gy in reirradiation [12,27,32,37-38,44-45]. Both RTOG® phase II studies used an accelerated hyperfractiona