Vol. 117 No. 2 February 2014
T4 squamous cell carcinoma of the oral tongue without mandibular involvement: surgery or chemoradiotherapy? Lachlan McDowell, MBBS, BAppSci,a Marnie Collins, BSci(Hons),b Stephen Kleid, FRACS, MBBS,c Danny Rischin, MD, FRACP, MBBS,d and June Corry, MD, FRACP, FRANZCR, MBBSa Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Objective. To investigate disease control and functional outcomes in patients with T4 squamous cell carcinoma of the oral tongue who had undergone surgery or definitive chemoradiotherapy. Study Design. Records of all consecutive patients with T4 squamous cell carcinoma of the oral tongue treated radically between 1999 and 2010 at the Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia, were retrospectively reviewed. Results. Of 31 patients, 19 underwent surgery and 12 underwent definitive chemoradiotherapy. There were no significant differences between cohorts in terms of age, nodal involvement, or performance status. All patients had T4 disease on the basis of extrinsic muscle invasion; none had bone invasion. Disease outcomes at 5 years after surgery or chemoradiotherapy were not significantly different, including local control (61% vs 70%), progression-free rate (56% vs 55%), and overall survival (27% vs 40%). A higher proportion of patients in the chemoradiotherapy group had only mild impairment of speech and swallowing. Conclusions. Definitive chemoradiotherapy may be a reasonable alternative to surgery for patients with T4 squamous cell carcinoma of the oral tongue without bony invasion. (Oral Surg Oral Med Oral Pathol Oral Radiol 2014;117:163-169)
Treatment of locally advanced squamous cell carcinoma (SCC) arising from head and neck mucosa is sitespecific, and many sites are treated definitively with concurrent chemoradiotherapy. SCC arising in the oral cavity has been shown in many series to have inferior outcomes compared with SCC in other head and neck subsites,1,2 and SCCs arising in the oral tongue have been shown to have a worse prognosis than those arising in other sites within the oral cavity, with high rates of local recurrence following definitive treatment.3,4 A study of 6791 patients with stage I and II oral cavity tumors from the Surveillance, Epidemiology, and End Results (SEER) database demonstrated 5-year overall and cause-specific survival rates of 60.9% and 83.5% for the oral tongue and 64.7% and 94.1% for other oral cavity subsites.2 This study also showed that early stage I and II oral tongue cancers have a significantly worse causespecific survival rate than do advanced stage III (hazard This study was presented in poster format at the Australian and New Zealand Head and Neck Cancer Society Annual Scientific Meeting and the International Federation of Head and Neck Oncologic Societies 2012 World Tour, Brisbane, Queensland, Australia, October 2426, 2012. a Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre. b Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre. c Division of Surgical Oncology, Peter MacCallum Cancer Centre. d Department of Medical Oncology, Peter MacCallum Cancer Centre. Received for publication Apr 2, 2013; returned for revision Aug 21, 2013; accepted for publication Sep 9, 2013. Crown Copyright Ó 2014 Published by Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter http://dx.doi.org/10.1016/j.oooo.2013.09.005
ratio [HR], 1.70; P < .001) and stage IV (HR, 1.56; P < .001) oropharyngeal cancers. The recommended standard of care for patients presenting with T4 oral tongue carcinoma is surgical excision followed by postoperative radiotherapy with or without concurrent chemotherapy.5 There are no prospective trials evaluating oncologic or functional outcomes comparing this approach with definitive chemoradiotherapy, which has generally been reserved for those patients who refuse the morbidity of surgery or are surgically or medically inoperable. It has traditionally been perceived that the treatment of oral cavity tumors with radiotherapy is associated with high treatment toxicity and poor efficacy. Our institutional policy for treatment of T4 oral tongue SCC was in accordance with international guidelines of adequate surgical resection followed by adjuvant radiotherapy with or without chemotherapy. It has generally been thought that this approach provides the best locoregional control, albeit at the potential cost of poorer functional outcomes. Patients who refused primary surgery were treated with definitive chemoradiotherapy if medically suitable. The aim of this study was to review the disease and
Statement of Clinical Relevance Surgery followed by adjuvant therapy is the standard of care in T4 squamous cell carcinoma of the oral tongue. This article offers a retrospective review of the experience in treating this entity with definitive chemoradiotherapy or surgery at a tertiary oncology center. 163
ORAL AND MAXILLOFACIAL SURGERY 164 McDowell et al.
long-term functional outcomes of patients presenting with T4 oral tongue SCC treated at our institution.
METHODS AND MATERIALS Data extraction All patients with T4 oral tongue SCC treated with radical (curative) intent at the Peter MacCallum Cancer Centre (PMCC; Melbourne, Victoria, Australia) between October 1999 and November 2010 were identified from an electronic database. Pathology and radiology were reviewed on all cases to confirm the staging. Medical records were retrospectively reviewed for disease and functional outcomes. Exclusion criteria included tumors arising in the base of the tongue with extension into the oral tongue and treatment with palliative intent. The study was approved by our institutional ethics committee. Staging Staging was in accordance with the American Joint Committee on Cancer’s Cancer Staging Manual, seventh edition.6 Pretreatment assessment was undertaken by the referring surgeon before definitive resection (in this setting, all patients were assessed by a radiation oncologist postoperatively before commencement of radiotherapy) or by the treating radiation oncologist before definitive chemoradiotherapy. A medical history and examination, an examination under anesthesia, and computed tomography scanning of the neck and chest were performed in all patients. Staging fluorodeoxyglucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) were used in 55% and 58% of cases, respectively, and were more frequently performed in the chemoradiotherapy cohort. Treatment All patients were discussed at a multidisciplinary head and neck meeting. Patients undergoing radical resection underwent either a total or near-total glossectomy or a hemiglossectomy with a unilateral or bilateral neck dissection. Patients were managed surgically at PMCC or at other metropolitan or regional hospitals within the Victorian Health System. All patients undergoing radiotherapy as a component of their management were treated at PMCC. In the adjuvant setting, the departmental policy is a radiotherapy prescription defined as follows, all delivered at daily 2-Gy fractions, 5 times per week: (1) 70 Gy to gross macroscopic residual disease; (2) 66 Gy to microscopically close or positive margins or regions of extracapsular nodal extension; (3) 60 Gy to microscopically clear disease (defined by a surgical margin of at least 2 mm) at both primary and
OOOO February 2014
nodal sites; and (4) 50 Gy to elective nodal stations. Standard concurrent chemotherapy during this time at our institution was weekly cisplatin, with carboplatin being substituted if there was a contraindication to cisplatin. Definitive chemoradiotherapy was delivered as a shrinking field technique at 2 Gy per fraction per day, 5 fractions per week, to a total dose of 70 Gy to macroscopic disease, 60 Gy to high-risk nodal stations, and 50 Gy to prophylactic nodal stations. Patients who received intensity-modulated radiotherapy (IMRT) were treated with a simultaneous integrated boost technique with dose correction for an increase in overall treatment time of 0.6 Gy per day. Standard concurrent chemotherapy in the definitive chemoradiotherapy setting was high-dose cisplatin administered every 3 weeks. All patients were assessed and monitored by dietetics staff while undergoing radiotherapy. Speech pathologist opinion was sought as required. Follow-up After resolution of acute radiation toxicities, patients treated surgically were usually discharged to their surgeon for follow-up. Patients who underwent definitive chemoradiotherapy were followed up by a radiation oncologist until death or discharge. A 3-month posttreatment FDG-PET scan was used to assess metabolic tumor response in patients treated in the latter years of this study. Functional assessment Toxicity grading was performed using the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03.7 Documentation from treating and external clinicians, speech therapists, and dietitians, as well as direct contact with primary care physicians, were used to grade late toxicity. Functional outcomes were assessed in patients who survived more than 3 months following completion of treatment. Functional outcomes were assessed as the best functional outcome achieved 3 months after completion of chemoradiotherapy until death or last follow-up. A secondary analysis was performed on those patients who had no evidence of disease 3 months posttreatment. Statistical analysis Survival curves estimated using the Kaplan-Meier product-limit method and annual survival rates with associated 95% confidence intervals (95% CI) were calculated for the time-to-event endpoints including overall survival, cancer-specific survival, time to progression, and time to locoregional and local failure. A series of univariate Cox proportional hazards regression models were fitted to assess the association
OOOO Volume 117, Number 2
of treatment modality (surgery vs chemoradiotherapy) with these endpoints. The assumption of proportional hazards between the treatment modalities was tested in each case, and the hazard ratio and corresponding 95% CI were calculated. Multifactor models accounting for the potential confounding variables of age at treatment commencement, nodal stage, and Eastern Cooperative Oncology Group (ECOG) performance status score were also considered. Associations between treatment modality and the best speech and swallowing functional outcomes achieved at least 3 months after treatment were investigated using the nonparametric Wilcoxon signed-rank test.
RESULTS Patient and tumor characteristics A total of 31 patients met the study criteria for inclusion. Of these, 19 patients underwent definitive surgery, and 12 patients were treated with definitive chemoradiotherapy. Patient characteristics are presented in Table I. There was no significant difference between the cohorts with respect to age (P ¼ .77), nodal staging (P ¼ .44), or performance status (P ¼ .89). All cancers were classified T4 due to soft tissue invasion. Patients were not excluded based on the presence of bone invasion, but no patient had evidence of pathologic invasion in the surgical arm or radiologic invasion in the chemoradiotherapy group. Treatment characteristics: surgical series Seven patients (37%) underwent near-total or total glossectomy, but none required total laryngectomy. The remaining 12 patients (63%) underwent a hemiglossectomy. The mean maximal tumor dimension was 45.2 mm (range, 24-70 mm). Extracapsular nodal disease was reported in 8 patients (42%). The majority of tumors were moderately (53%) or poorly (37%) differentiated. Margins were involved in 3 patients (16%), close (
T4 squamous cell carcinoma of the oral tongue without mandibular involvement: surgery or chemoradiotherapy? Lachlan McDowell, MBBS, BAppSci,a Marnie Collins, BSci(Hons),b Stephen Kleid, FRACS, MBBS,c Danny Rischin, MD, FRACP, MBBS,d and June Corry, MD, FRACP, FRANZCR, MBBSa Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Objective. To investigate disease control and functional outcomes in patients with T4 squamous cell carcinoma of the oral tongue who had undergone surgery or definitive chemoradiotherapy. Study Design. Records of all consecutive patients with T4 squamous cell carcinoma of the oral tongue treated radically between 1999 and 2010 at the Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia, were retrospectively reviewed. Results. Of 31 patients, 19 underwent surgery and 12 underwent definitive chemoradiotherapy. There were no significant differences between cohorts in terms of age, nodal involvement, or performance status. All patients had T4 disease on the basis of extrinsic muscle invasion; none had bone invasion. Disease outcomes at 5 years after surgery or chemoradiotherapy were not significantly different, including local control (61% vs 70%), progression-free rate (56% vs 55%), and overall survival (27% vs 40%). A higher proportion of patients in the chemoradiotherapy group had only mild impairment of speech and swallowing. Conclusions. Definitive chemoradiotherapy may be a reasonable alternative to surgery for patients with T4 squamous cell carcinoma of the oral tongue without bony invasion. (Oral Surg Oral Med Oral Pathol Oral Radiol 2014;117:163-169)
Treatment of locally advanced squamous cell carcinoma (SCC) arising from head and neck mucosa is sitespecific, and many sites are treated definitively with concurrent chemoradiotherapy. SCC arising in the oral cavity has been shown in many series to have inferior outcomes compared with SCC in other head and neck subsites,1,2 and SCCs arising in the oral tongue have been shown to have a worse prognosis than those arising in other sites within the oral cavity, with high rates of local recurrence following definitive treatment.3,4 A study of 6791 patients with stage I and II oral cavity tumors from the Surveillance, Epidemiology, and End Results (SEER) database demonstrated 5-year overall and cause-specific survival rates of 60.9% and 83.5% for the oral tongue and 64.7% and 94.1% for other oral cavity subsites.2 This study also showed that early stage I and II oral tongue cancers have a significantly worse causespecific survival rate than do advanced stage III (hazard This study was presented in poster format at the Australian and New Zealand Head and Neck Cancer Society Annual Scientific Meeting and the International Federation of Head and Neck Oncologic Societies 2012 World Tour, Brisbane, Queensland, Australia, October 2426, 2012. a Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre. b Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre. c Division of Surgical Oncology, Peter MacCallum Cancer Centre. d Department of Medical Oncology, Peter MacCallum Cancer Centre. Received for publication Apr 2, 2013; returned for revision Aug 21, 2013; accepted for publication Sep 9, 2013. Crown Copyright Ó 2014 Published by Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter http://dx.doi.org/10.1016/j.oooo.2013.09.005
ratio [HR], 1.70; P < .001) and stage IV (HR, 1.56; P < .001) oropharyngeal cancers. The recommended standard of care for patients presenting with T4 oral tongue carcinoma is surgical excision followed by postoperative radiotherapy with or without concurrent chemotherapy.5 There are no prospective trials evaluating oncologic or functional outcomes comparing this approach with definitive chemoradiotherapy, which has generally been reserved for those patients who refuse the morbidity of surgery or are surgically or medically inoperable. It has traditionally been perceived that the treatment of oral cavity tumors with radiotherapy is associated with high treatment toxicity and poor efficacy. Our institutional policy for treatment of T4 oral tongue SCC was in accordance with international guidelines of adequate surgical resection followed by adjuvant radiotherapy with or without chemotherapy. It has generally been thought that this approach provides the best locoregional control, albeit at the potential cost of poorer functional outcomes. Patients who refused primary surgery were treated with definitive chemoradiotherapy if medically suitable. The aim of this study was to review the disease and
Statement of Clinical Relevance Surgery followed by adjuvant therapy is the standard of care in T4 squamous cell carcinoma of the oral tongue. This article offers a retrospective review of the experience in treating this entity with definitive chemoradiotherapy or surgery at a tertiary oncology center. 163
ORAL AND MAXILLOFACIAL SURGERY 164 McDowell et al.
long-term functional outcomes of patients presenting with T4 oral tongue SCC treated at our institution.
METHODS AND MATERIALS Data extraction All patients with T4 oral tongue SCC treated with radical (curative) intent at the Peter MacCallum Cancer Centre (PMCC; Melbourne, Victoria, Australia) between October 1999 and November 2010 were identified from an electronic database. Pathology and radiology were reviewed on all cases to confirm the staging. Medical records were retrospectively reviewed for disease and functional outcomes. Exclusion criteria included tumors arising in the base of the tongue with extension into the oral tongue and treatment with palliative intent. The study was approved by our institutional ethics committee. Staging Staging was in accordance with the American Joint Committee on Cancer’s Cancer Staging Manual, seventh edition.6 Pretreatment assessment was undertaken by the referring surgeon before definitive resection (in this setting, all patients were assessed by a radiation oncologist postoperatively before commencement of radiotherapy) or by the treating radiation oncologist before definitive chemoradiotherapy. A medical history and examination, an examination under anesthesia, and computed tomography scanning of the neck and chest were performed in all patients. Staging fluorodeoxyglucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) were used in 55% and 58% of cases, respectively, and were more frequently performed in the chemoradiotherapy cohort. Treatment All patients were discussed at a multidisciplinary head and neck meeting. Patients undergoing radical resection underwent either a total or near-total glossectomy or a hemiglossectomy with a unilateral or bilateral neck dissection. Patients were managed surgically at PMCC or at other metropolitan or regional hospitals within the Victorian Health System. All patients undergoing radiotherapy as a component of their management were treated at PMCC. In the adjuvant setting, the departmental policy is a radiotherapy prescription defined as follows, all delivered at daily 2-Gy fractions, 5 times per week: (1) 70 Gy to gross macroscopic residual disease; (2) 66 Gy to microscopically close or positive margins or regions of extracapsular nodal extension; (3) 60 Gy to microscopically clear disease (defined by a surgical margin of at least 2 mm) at both primary and
OOOO February 2014
nodal sites; and (4) 50 Gy to elective nodal stations. Standard concurrent chemotherapy during this time at our institution was weekly cisplatin, with carboplatin being substituted if there was a contraindication to cisplatin. Definitive chemoradiotherapy was delivered as a shrinking field technique at 2 Gy per fraction per day, 5 fractions per week, to a total dose of 70 Gy to macroscopic disease, 60 Gy to high-risk nodal stations, and 50 Gy to prophylactic nodal stations. Patients who received intensity-modulated radiotherapy (IMRT) were treated with a simultaneous integrated boost technique with dose correction for an increase in overall treatment time of 0.6 Gy per day. Standard concurrent chemotherapy in the definitive chemoradiotherapy setting was high-dose cisplatin administered every 3 weeks. All patients were assessed and monitored by dietetics staff while undergoing radiotherapy. Speech pathologist opinion was sought as required. Follow-up After resolution of acute radiation toxicities, patients treated surgically were usually discharged to their surgeon for follow-up. Patients who underwent definitive chemoradiotherapy were followed up by a radiation oncologist until death or discharge. A 3-month posttreatment FDG-PET scan was used to assess metabolic tumor response in patients treated in the latter years of this study. Functional assessment Toxicity grading was performed using the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03.7 Documentation from treating and external clinicians, speech therapists, and dietitians, as well as direct contact with primary care physicians, were used to grade late toxicity. Functional outcomes were assessed in patients who survived more than 3 months following completion of treatment. Functional outcomes were assessed as the best functional outcome achieved 3 months after completion of chemoradiotherapy until death or last follow-up. A secondary analysis was performed on those patients who had no evidence of disease 3 months posttreatment. Statistical analysis Survival curves estimated using the Kaplan-Meier product-limit method and annual survival rates with associated 95% confidence intervals (95% CI) were calculated for the time-to-event endpoints including overall survival, cancer-specific survival, time to progression, and time to locoregional and local failure. A series of univariate Cox proportional hazards regression models were fitted to assess the association
OOOO Volume 117, Number 2
of treatment modality (surgery vs chemoradiotherapy) with these endpoints. The assumption of proportional hazards between the treatment modalities was tested in each case, and the hazard ratio and corresponding 95% CI were calculated. Multifactor models accounting for the potential confounding variables of age at treatment commencement, nodal stage, and Eastern Cooperative Oncology Group (ECOG) performance status score were also considered. Associations between treatment modality and the best speech and swallowing functional outcomes achieved at least 3 months after treatment were investigated using the nonparametric Wilcoxon signed-rank test.
RESULTS Patient and tumor characteristics A total of 31 patients met the study criteria for inclusion. Of these, 19 patients underwent definitive surgery, and 12 patients were treated with definitive chemoradiotherapy. Patient characteristics are presented in Table I. There was no significant difference between the cohorts with respect to age (P ¼ .77), nodal staging (P ¼ .44), or performance status (P ¼ .89). All cancers were classified T4 due to soft tissue invasion. Patients were not excluded based on the presence of bone invasion, but no patient had evidence of pathologic invasion in the surgical arm or radiologic invasion in the chemoradiotherapy group. Treatment characteristics: surgical series Seven patients (37%) underwent near-total or total glossectomy, but none required total laryngectomy. The remaining 12 patients (63%) underwent a hemiglossectomy. The mean maximal tumor dimension was 45.2 mm (range, 24-70 mm). Extracapsular nodal disease was reported in 8 patients (42%). The majority of tumors were moderately (53%) or poorly (37%) differentiated. Margins were involved in 3 patients (16%), close (
