- Email: [email protected]
Head and neck cancer with lower neck nodal metastases: Management of 23 cases and review of the literature
Oral Oncology 48 (2012) 325–328
Contents lists available at SciVerse ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Short Communication
Head and neck cancer with lower neck nodal metastases: Management of 23 cases and review of the literature q Federico L. Ampil a,⇑, Cherie-Ann O. Nathan b, Guillermo Sangster a, Gloria Caldito c a
Department of Radiology, Louisiana State University Health Sciences Center and Feist-Weiller Cancer Center, Shreveport, LA 71130, USA Department of Otolaryngology Head and Neck Surgery, Louisiana State University Health Sciences Center and Feist-Weiller Cancer Center, Shreveport, LA 71130, USA c Department of Biometry, Louisiana State University Health Sciences Center and Feist-Weiller Cancer Center, Shreveport, LA 71130, USA b
a r t i c l e
i n f o
Article history: Received 23 August 2011 Received in revised form 16 November 2011 Accepted 21 November 2011 Available online 9 March 2012 Keywords: Total laryngectomy Radiotherapy Chemotherapy Lower neck nodal metastases Modified neck dissection Oropharynx cancer Larynx cancer
s u m m a r y To investigate the patient outcomes associated with the applied modes of therapy in head and neck cancer with lower neck nodal metastases. The medical records of 23 consecutive individuals who were managed by intent to treat for head and neck cancer with metastatic disease in the lower neck nodes over a 19-year period were reviewed. The mean age was 53.5 years, and the larynx was the most frequently affected primary site (57%). Overall, locoregional tumor control was achieved in the majority (75%) of the cases and the 2-year survival rate was 48%. The 2-year survival rates of people managed by surgery and postoperative radiotherapy, chemoradiation or single modality therapy were 63%, 56% and 17%, respectively, (p = 0.04). Aggressive therapy resulted in five (22%) long-term (>5 years) survivors. The combination of treatment modalities proved to be effective management for head and neck cancer with lower neck nodal metastases and should be further investigated in prospective trials. Ó 2011 Elsevier Ltd. All rights reserved.
Introduction Lymph nodes which occupy the lowermost part of the neck, include level IV or supraclavicular nodes. Lower neck nodal metastases (LNNM) in people with head and neck cancer (HNC) represent advanced disease with some chance of cure. Because of the infrequency of HNC–LNNM, the optimal management of such a complicated neoplastic condition is not well documented. This retrospective study describes the experience with the management of patients with HNC–LNNM over a 19-year period. Patients and methods After obtaining approval from the Institutional Review Board, a review of the radiation oncology records and imaging and pathology reports was performed to identify the subjects of this clinical investigation. From a total of 2275 HNC patients, 23 people (1%) were managed with intent to treat for HNC–LNNM between 1989 and 2007. The diagnosis of LNNM was based on abnormal palpable q To be presented in part at the Multidisciplinary Symposium on Head and Neck Cancer, Phoenix, Arizona, January 26, 2012. ⇑ Corresponding author. Address: Division of Therapeutic Radiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA. Tel.: +1 318 675 5334; fax: +1 318 675 4697. E-mail address: [email protected] (F.L. Ampil).
1368-8375/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.oraloncology.2011.11.016
disease on physical examination (two patients) and nodal abnormality according to accepted criteria on computed tomography (three patients; Fig. 1), or positron emission tomography (seven patients) or histologically proven metastatic disease (11 patients). The individuals were classified into three groups: those who underwent definitive surgery and postoperative radiotherapy (group A, eight patients), those who were treated by chemoradiation (group B, nine patients), and those who received single modality therapy (group C, six patients). Definitive surgery for laryngeal cancer usually consisted of total laryngectomy (with partial pharyngectomy in one patient) and modified neck dissection of levels II–IV nodes. Patients with oral cavity cancer were managed by composite tumor resection with neck dissection of levels I–IV nodes. With regard to definitive radiotherapy (defined as irradiation with an administered dose of P66 Gy), the mean dose to the primary tumor site including the upper neck was 68.6 Gy and to the lower neck 50 Gy; the corresponding mean values for postoperative irradiation were 59.6 and 53.5 Gy. Chemotherapy, on the other hand, consisted of several cycles of Cisplatin and/or 5-Fluorouracil. The details of external beam irradiation and 2-drug chemotherapy use have been described in previous reports.1,2 The median follow-up was 19 months (range 1–122 months). The Kaplan–Meier method was used to calculate cumulative survival. Death from any cause was considered in the measurement of overall survival. Longevity was estimated from the date of
326
F.L. Ampil et al. / Oral Oncology 48 (2012) 325–328
were >15, >9 and 9 months. The comparison of patient groups (which included the single modality managed people) may not be appropriate considering that some individuals received only an abbreviated radiation scheme for palliation or were not able to complete the prescribed therapy course. Nonetheless, there were five (22%) long-term (>5 years) survivors, and all of these patients received combined therapy for their HNC–LNNM lesions. An unexpected and interesting finding was the median survival of 11.5 months for the clinically diagnosed LNNMs and 36.5 months for the histologically proven metastases in the lower neck. Acute toxicity associated with employed treatment combinations and quality of life evaluations after therapy were poorly documented in the available records of many patients. Discussion
Figure 1 Computed tomography shows adenopathies in the supraclavicular spaces.
HNC diagnosis to the date of death or last follow-up. Differences in survival for the employed methods of treatment were compared using the log rank test. Level of significance was p < 0.05. Results There were 16 men and seven women with a mean age of 53.5 years (range 33–77 years). The primary neoplasms were located in the larynx (12 cases), oropharynx (five cases), and in the oral cavity, nasopharynx, or combination thereof (five cases). In one case, metastatic disease from an unknown primary site was observed at levels III and IV of the neck. LNNM was present alone (eight patients) or was accompanied by other clinically exhibited or imaging-shown cervical nodal metastatic disease at level 2 (13 patients), level 3 (13 patients), and level 7 (two patients). Stage IV HNC was present in 20 people (87%), as shown in Tables 1–3. Seven patients (30%) were alive, and their follow-up ranged from 44 to 122 months (Table 4). Sixteen patients have died, and their period of survival ranged from 1 to 111 months. Among the 20 individuals evaluable for malignant disease status after therapy, 15 patients (75%) were free of HNC–LNNM prior to death or at last contact; four people (20%) have died with local and/or regional disease, and one patient was dead from locally advanced (distal esophageal) second primary malignancy. The overall 2-year survival rate was 48% (Fig. 2) and the median survival was 19 months. The 2-year survival rates for groups A, B and C were 63%, 56% and 17%, respectively (p = 0.04); the corresponding median survivals
HNC–LNNM is an uncommon disease entity. In the original report about the distribution of neoplastic spread to the nodes in the neck involving 1081 patients with squamous cell carcinomas of the upper aerodigestive tract, level IV lymph nodes were the least affected compared to levels II and III nodes.3 Because of the very limited accounts of HNC–LNNM, it is important to understand the potential gains of applied care. Due to the generally held tenet that metastatic spread to the nodes is advanced stage disease, a rational decision regarding management is to treat these individuals by either surgery and postoperative radiotherapy, with or without chemotherapy, or by chemoradiotherapy when a contraindication to operative intervention exists. In this retrospective study, the overall 2-year survival rate was 48%, and the locoregional tumor control rate was 75%. Moreover, our results showed that combined therapy for this especial condition yielded better prognosis (including long-term survival) compared to single modality treatment. Review of the literature revealed that the 5-year disease-specific survival rate was 60% when the lower jugular nodes contained metastatic disease; such an acceptable outcome was from an experience of treating 136 people utilizing a consistent management policy of combined surgery and postoperative radiotherapy for metastatic squamous cell carcinoma to the cervical lymph nodes from an unknown primary site.4 On the other hand, when a non-operative management approach consisting of radiotherapy or chemotherapy alone or a combination thereof was employed in 41 patients with metastatic squamous or poorly differentiated carcinoma of unknown origin, the observed 5-year survival rates ranged from 13% to 25%.5 Conventional wisdom about HNC involving the lymph nodes of the neck is that the lower the adenopathy in the cervical nodal chain affected by tumor, the poorer the prognosis. From an
Table 1 Surgery with postoperative radiotherapy. Case No.
Age in years
Tumor Site
1 2 3 4 5 6 7 8 a
50 70 41 50 61 52 57 54
a
OPX-LYX-HPX LYX LYX LYX OC LYX LYX LYX
Stage
Surgeryc
Radiotherapy dosed (Gy)
Outcomee
Follow-up in months
TLND TLND TLND TLND TJND TLND TLND TL-P-ND
60–50 60–50 58–50 60–60 60–60 60–50 59–54 60–54
DNED DNED ANED DNED DNED ANED DNED DWSPM
111 11 102 54 19 122 62 15
b
T4N2M0 T2N0M0 T4N2M0 T4N2M0 T4N2M0 T4N2M0 T4N2M0 T3N2M0
OPX = oropharynx; LYX = larynx; HPX = hypopharynx; OC = oral cavity. Stage according to the American Joint Committee on Cancer system. TLND = total laryngectomy and neck dissection; TJND = composite tumor resection and neck dissection; TL-P-ND = total laryngectomy, partial pharyngectomy and neck dissection. d Dose for resected gross tumor – dose for subclinical disease. e DNED = died without cancer; ANED = alive without cancer; DWSPM = died with second primary cancer. b
c
327
F.L. Ampil et al. / Oral Oncology 48 (2012) 325–328 Table 2 Chemotherapy with radiotherapy. Case No.
Age in years
Tumor Site
1 2 3 4 5 6 7 8 9 a b c d e
63 59 33 40 52 50 56 71 49
a
Stage
LYX OPX NSPX OPX NSPX LYX NMUP OPX LYX
Chemotherapyc
Radiotherapy dosed (Gy)
Outcomee
Follow-up in months
CisPT CisPT-5FU CisPT-5FU CisPT CisPT-5FU CisPT CisPT CisPT-5FU CisPT-5FU
70–50 60–50 66–50 60–50 50–45 63–50 70–50 68–50 68–50
DNED DWRD DNED ANED DNED ANED ANED ANED DIED
29 4 6 54 17 44 58 88 9
b
T3N2M0 T1N3M0 T2N3M0 T3N2M0 T2N2M0 T4N2M0 TXN2M0 T2N2M0 T2N1M0
LYX = larynx; OPX = oropharynx; NSPX = nasopharynx; NMUP = neck metastasis from unknown primary site. Stage according to the American Joint Committee on Cancer system. CisPT = Cisplatin; 5-FU = 5-Fluorouracil. Dose for gross tumor – dose for subclinical disease. DNED = died without cancer; DWRD = died with regional disease; ANED = alive without cancer.
Table 3 Single modality treatment. Case No.
1 2 3 4 5 6 a b c d e
Age in years
40 57 46 77 46 58
Tumor Sitea
Stageb
LYX OPX LYX OPX LYX LYX-HPX
T3N0M0 T4N3M1 T4N3M0 T2N2M0 T4N2M0 T4N3M1
Treatmentc
Radiotherapy dosed (Gy)
Outcomee
Follow-up in months
TLND PXRT IXRT DXRT TLND PXRT
– 40–40 22–22 70–50 – 60–50
DIED DWLRD DWLRD DIED ANED DWLRD
9 14 1 9 58 1
LYX = larynx; OPX = oropharynx; LYX-HPX = laryngohypopharynx. Stage according to American Joint Committee on Cancer system; M1 = abnormal level 7 adenopathy detected on CT or PET imaging. TLND = total laryngectomy and neck dissection; PXRT = palliative radiotherapy; IXRT = incomplete radiotherapy; DXRT = definitive radiotherapy. Dose for gross tumor – dose for subclinical disease. DWLRD = died with locoregional disease; ANED = alive without cancer.
Table 4 Treatment and outcome. Outcome
* **
Therapy Single
Bimodal
Alive* Without cancer
(1)
(6)
Died** Without cancer With local/regional cancer With second primary cancer Cancer status unknown
– (3) – (2)
(8) (1) (1) (1)
Follow-up (range 44–122 months). Survival (range 1–111 months).
investigation of the effect of node level on survival involving 2058 patients with HNC, the 5-year survival rate was only 4% when level 4 nodal metastatic spread was documented.6 In a lymph node dissection report of 914 individuals with HNC at the Institut Gustave-Roussy, the 5-year survival rates were 38%, 25% and 5% when metastases were present in the upper, middle and lower jugular nodes, respectively.7 Such differing prognoses were also observed in other similar accounts of cervical metastases from an unknown primary site in the head and neck region.8,9 Our hypothesis to explain the dismal outcome seen in these individuals with HNC– LNNM stems from the fact that there are more frequent appearances of distant metastases whenever metastatic neoplasm is found in the lower jugular nodes of the neck.7,10 Furthermore, another proposition could be the occurrence of neoplastic spread to the mediastinal nodes. In a review of their elective superior mediastinal node dissection experience of 56 patients (42 with
Figure 2 Overall survival of 23 head and neck cancer patients with lower neck nodal metastases after intent to treat.
advanced laryngeal cancer and 14 with overt level 4 adenopathy), Oxford and Ducic11 detected occult mediastinal metastases in 27% of the evaluated people. The limitations of this study include its retrospective design, small sample size, variability of primary tumor sites and applied therapy, and the point that not all LNNMs were histologically confirmed and selection bias. These considerations certainly warrant cautious interpretation of the results and preclude a definite conclusion regarding best treatment. Nonetheless, this investigation is distinguished by its focus on the assessment of benefits obtained from an intent-to-treat management policy.
328
F.L. Ampil et al. / Oral Oncology 48 (2012) 325–328
In conclusion, this study suggests that the treatment of patients with HNC–LNNM needs to be aggressive. We believe in the adoption of an individualized management approach using a combination of treatment modes (i.e., preference for definitive surgery with postoperative radiotherapy/chemoradiation in cases of resectable lesions and chemoradiotherapy for unresectable disease) for this complicated neoplastic condition. Whether such combined therapy care truly has positive effects on survival deserves additional investigation. Conflict of interest statement None declared. References 1. Ampil FL, Datta R, Shockley W. Adjuvant postoperative external beam radiotherapy in head and neck cancer. J Oral Maxillofac Surg 1988;46:569–73. 2. Cho AH, Shah S, Ampil F, Bhartur S, Nathan CAO. N2 disease in patients with head and neck squamous cell cancer treated with chemoradiotherapy. Arch Otolaryngol Head Neck Surg 2009;135:1112–8.
3. Shah JP. Patterns of cervical lymph node metastasis for squamous cell carcinomas of the upper aerodigestive tract. Am J Surg 1990;160:405–9. 4. Colletier PJ, Garden AS, Morrison WH, Goepfert H, Geara F, Ang K. Postoperative radiotherapy for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site: outcomes and patterns of failure. Head Neck 1998;20:674–81. 5. Yalin Y, Pingzhang T, Smith GI, Ilankovan V. Management and outcome of cervical lymph node metastases of unknown primary sites: a retrospective study. Br J Oral Maxillofac Surg 2002;40:484–7. 6. Stell PM, Morton RP, Singh SD. Cervical lymph node metastases: the significance of the level of the lymph node. Clin Oncol 1983;9:101–7. 7. Mamelle G, Pampurik J, Luboinski B, Lancar R, Lusinchi A, Bosq J. Lymph node prognostic factors in head and neck squamous cell carcinomas. Am J Surg 1994;168:494–8. 8. Huang CC, Tseng FY, Yeh TH, Wen YH, Hsu CJ, Ko JY, et al. Prognostic factors of unknown primary head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg 2008;139:429–35. 9. Issing WJ, Taleban B, Tauber S. Diagnosis and management of carcinoma of unknown primary in the head and neck. Eur Arch Otorhinolaryngol 2003;260:436–43. 10. Shingaki S, Takada M, Sasai K, Bibi R, Kobayashi T, Nomura T, et al. Impact of lymph node metastasis on the pattern of failure and survival in oral carcinomas. Am J Surg 2003;185:278–84. 11. Oxford LE, Ducic Y. Elective transcervical superior mediastinal lymph node dissection for advanced laryngeal and level 4 N3 squamous cell carcinoma. Laryngoscope 2005;115:625–8.
Contents lists available at SciVerse ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Short Communication
Head and neck cancer with lower neck nodal metastases: Management of 23 cases and review of the literature q Federico L. Ampil a,⇑, Cherie-Ann O. Nathan b, Guillermo Sangster a, Gloria Caldito c a
Department of Radiology, Louisiana State University Health Sciences Center and Feist-Weiller Cancer Center, Shreveport, LA 71130, USA Department of Otolaryngology Head and Neck Surgery, Louisiana State University Health Sciences Center and Feist-Weiller Cancer Center, Shreveport, LA 71130, USA c Department of Biometry, Louisiana State University Health Sciences Center and Feist-Weiller Cancer Center, Shreveport, LA 71130, USA b
a r t i c l e
i n f o
Article history: Received 23 August 2011 Received in revised form 16 November 2011 Accepted 21 November 2011 Available online 9 March 2012 Keywords: Total laryngectomy Radiotherapy Chemotherapy Lower neck nodal metastases Modified neck dissection Oropharynx cancer Larynx cancer
s u m m a r y To investigate the patient outcomes associated with the applied modes of therapy in head and neck cancer with lower neck nodal metastases. The medical records of 23 consecutive individuals who were managed by intent to treat for head and neck cancer with metastatic disease in the lower neck nodes over a 19-year period were reviewed. The mean age was 53.5 years, and the larynx was the most frequently affected primary site (57%). Overall, locoregional tumor control was achieved in the majority (75%) of the cases and the 2-year survival rate was 48%. The 2-year survival rates of people managed by surgery and postoperative radiotherapy, chemoradiation or single modality therapy were 63%, 56% and 17%, respectively, (p = 0.04). Aggressive therapy resulted in five (22%) long-term (>5 years) survivors. The combination of treatment modalities proved to be effective management for head and neck cancer with lower neck nodal metastases and should be further investigated in prospective trials. Ó 2011 Elsevier Ltd. All rights reserved.
Introduction Lymph nodes which occupy the lowermost part of the neck, include level IV or supraclavicular nodes. Lower neck nodal metastases (LNNM) in people with head and neck cancer (HNC) represent advanced disease with some chance of cure. Because of the infrequency of HNC–LNNM, the optimal management of such a complicated neoplastic condition is not well documented. This retrospective study describes the experience with the management of patients with HNC–LNNM over a 19-year period. Patients and methods After obtaining approval from the Institutional Review Board, a review of the radiation oncology records and imaging and pathology reports was performed to identify the subjects of this clinical investigation. From a total of 2275 HNC patients, 23 people (1%) were managed with intent to treat for HNC–LNNM between 1989 and 2007. The diagnosis of LNNM was based on abnormal palpable q To be presented in part at the Multidisciplinary Symposium on Head and Neck Cancer, Phoenix, Arizona, January 26, 2012. ⇑ Corresponding author. Address: Division of Therapeutic Radiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA. Tel.: +1 318 675 5334; fax: +1 318 675 4697. E-mail address: [email protected] (F.L. Ampil).
1368-8375/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.oraloncology.2011.11.016
disease on physical examination (two patients) and nodal abnormality according to accepted criteria on computed tomography (three patients; Fig. 1), or positron emission tomography (seven patients) or histologically proven metastatic disease (11 patients). The individuals were classified into three groups: those who underwent definitive surgery and postoperative radiotherapy (group A, eight patients), those who were treated by chemoradiation (group B, nine patients), and those who received single modality therapy (group C, six patients). Definitive surgery for laryngeal cancer usually consisted of total laryngectomy (with partial pharyngectomy in one patient) and modified neck dissection of levels II–IV nodes. Patients with oral cavity cancer were managed by composite tumor resection with neck dissection of levels I–IV nodes. With regard to definitive radiotherapy (defined as irradiation with an administered dose of P66 Gy), the mean dose to the primary tumor site including the upper neck was 68.6 Gy and to the lower neck 50 Gy; the corresponding mean values for postoperative irradiation were 59.6 and 53.5 Gy. Chemotherapy, on the other hand, consisted of several cycles of Cisplatin and/or 5-Fluorouracil. The details of external beam irradiation and 2-drug chemotherapy use have been described in previous reports.1,2 The median follow-up was 19 months (range 1–122 months). The Kaplan–Meier method was used to calculate cumulative survival. Death from any cause was considered in the measurement of overall survival. Longevity was estimated from the date of
326
F.L. Ampil et al. / Oral Oncology 48 (2012) 325–328
were >15, >9 and 9 months. The comparison of patient groups (which included the single modality managed people) may not be appropriate considering that some individuals received only an abbreviated radiation scheme for palliation or were not able to complete the prescribed therapy course. Nonetheless, there were five (22%) long-term (>5 years) survivors, and all of these patients received combined therapy for their HNC–LNNM lesions. An unexpected and interesting finding was the median survival of 11.5 months for the clinically diagnosed LNNMs and 36.5 months for the histologically proven metastases in the lower neck. Acute toxicity associated with employed treatment combinations and quality of life evaluations after therapy were poorly documented in the available records of many patients. Discussion
Figure 1 Computed tomography shows adenopathies in the supraclavicular spaces.
HNC diagnosis to the date of death or last follow-up. Differences in survival for the employed methods of treatment were compared using the log rank test. Level of significance was p < 0.05. Results There were 16 men and seven women with a mean age of 53.5 years (range 33–77 years). The primary neoplasms were located in the larynx (12 cases), oropharynx (five cases), and in the oral cavity, nasopharynx, or combination thereof (five cases). In one case, metastatic disease from an unknown primary site was observed at levels III and IV of the neck. LNNM was present alone (eight patients) or was accompanied by other clinically exhibited or imaging-shown cervical nodal metastatic disease at level 2 (13 patients), level 3 (13 patients), and level 7 (two patients). Stage IV HNC was present in 20 people (87%), as shown in Tables 1–3. Seven patients (30%) were alive, and their follow-up ranged from 44 to 122 months (Table 4). Sixteen patients have died, and their period of survival ranged from 1 to 111 months. Among the 20 individuals evaluable for malignant disease status after therapy, 15 patients (75%) were free of HNC–LNNM prior to death or at last contact; four people (20%) have died with local and/or regional disease, and one patient was dead from locally advanced (distal esophageal) second primary malignancy. The overall 2-year survival rate was 48% (Fig. 2) and the median survival was 19 months. The 2-year survival rates for groups A, B and C were 63%, 56% and 17%, respectively (p = 0.04); the corresponding median survivals
HNC–LNNM is an uncommon disease entity. In the original report about the distribution of neoplastic spread to the nodes in the neck involving 1081 patients with squamous cell carcinomas of the upper aerodigestive tract, level IV lymph nodes were the least affected compared to levels II and III nodes.3 Because of the very limited accounts of HNC–LNNM, it is important to understand the potential gains of applied care. Due to the generally held tenet that metastatic spread to the nodes is advanced stage disease, a rational decision regarding management is to treat these individuals by either surgery and postoperative radiotherapy, with or without chemotherapy, or by chemoradiotherapy when a contraindication to operative intervention exists. In this retrospective study, the overall 2-year survival rate was 48%, and the locoregional tumor control rate was 75%. Moreover, our results showed that combined therapy for this especial condition yielded better prognosis (including long-term survival) compared to single modality treatment. Review of the literature revealed that the 5-year disease-specific survival rate was 60% when the lower jugular nodes contained metastatic disease; such an acceptable outcome was from an experience of treating 136 people utilizing a consistent management policy of combined surgery and postoperative radiotherapy for metastatic squamous cell carcinoma to the cervical lymph nodes from an unknown primary site.4 On the other hand, when a non-operative management approach consisting of radiotherapy or chemotherapy alone or a combination thereof was employed in 41 patients with metastatic squamous or poorly differentiated carcinoma of unknown origin, the observed 5-year survival rates ranged from 13% to 25%.5 Conventional wisdom about HNC involving the lymph nodes of the neck is that the lower the adenopathy in the cervical nodal chain affected by tumor, the poorer the prognosis. From an
Table 1 Surgery with postoperative radiotherapy. Case No.
Age in years
Tumor Site
1 2 3 4 5 6 7 8 a
50 70 41 50 61 52 57 54
a
OPX-LYX-HPX LYX LYX LYX OC LYX LYX LYX
Stage
Surgeryc
Radiotherapy dosed (Gy)
Outcomee
Follow-up in months
TLND TLND TLND TLND TJND TLND TLND TL-P-ND
60–50 60–50 58–50 60–60 60–60 60–50 59–54 60–54
DNED DNED ANED DNED DNED ANED DNED DWSPM
111 11 102 54 19 122 62 15
b
T4N2M0 T2N0M0 T4N2M0 T4N2M0 T4N2M0 T4N2M0 T4N2M0 T3N2M0
OPX = oropharynx; LYX = larynx; HPX = hypopharynx; OC = oral cavity. Stage according to the American Joint Committee on Cancer system. TLND = total laryngectomy and neck dissection; TJND = composite tumor resection and neck dissection; TL-P-ND = total laryngectomy, partial pharyngectomy and neck dissection. d Dose for resected gross tumor – dose for subclinical disease. e DNED = died without cancer; ANED = alive without cancer; DWSPM = died with second primary cancer. b
c
327
F.L. Ampil et al. / Oral Oncology 48 (2012) 325–328 Table 2 Chemotherapy with radiotherapy. Case No.
Age in years
Tumor Site
1 2 3 4 5 6 7 8 9 a b c d e
63 59 33 40 52 50 56 71 49
a
Stage
LYX OPX NSPX OPX NSPX LYX NMUP OPX LYX
Chemotherapyc
Radiotherapy dosed (Gy)
Outcomee
Follow-up in months
CisPT CisPT-5FU CisPT-5FU CisPT CisPT-5FU CisPT CisPT CisPT-5FU CisPT-5FU
70–50 60–50 66–50 60–50 50–45 63–50 70–50 68–50 68–50
DNED DWRD DNED ANED DNED ANED ANED ANED DIED
29 4 6 54 17 44 58 88 9
b
T3N2M0 T1N3M0 T2N3M0 T3N2M0 T2N2M0 T4N2M0 TXN2M0 T2N2M0 T2N1M0
LYX = larynx; OPX = oropharynx; NSPX = nasopharynx; NMUP = neck metastasis from unknown primary site. Stage according to the American Joint Committee on Cancer system. CisPT = Cisplatin; 5-FU = 5-Fluorouracil. Dose for gross tumor – dose for subclinical disease. DNED = died without cancer; DWRD = died with regional disease; ANED = alive without cancer.
Table 3 Single modality treatment. Case No.
1 2 3 4 5 6 a b c d e
Age in years
40 57 46 77 46 58
Tumor Sitea
Stageb
LYX OPX LYX OPX LYX LYX-HPX
T3N0M0 T4N3M1 T4N3M0 T2N2M0 T4N2M0 T4N3M1
Treatmentc
Radiotherapy dosed (Gy)
Outcomee
Follow-up in months
TLND PXRT IXRT DXRT TLND PXRT
– 40–40 22–22 70–50 – 60–50
DIED DWLRD DWLRD DIED ANED DWLRD
9 14 1 9 58 1
LYX = larynx; OPX = oropharynx; LYX-HPX = laryngohypopharynx. Stage according to American Joint Committee on Cancer system; M1 = abnormal level 7 adenopathy detected on CT or PET imaging. TLND = total laryngectomy and neck dissection; PXRT = palliative radiotherapy; IXRT = incomplete radiotherapy; DXRT = definitive radiotherapy. Dose for gross tumor – dose for subclinical disease. DWLRD = died with locoregional disease; ANED = alive without cancer.
Table 4 Treatment and outcome. Outcome
* **
Therapy Single
Bimodal
Alive* Without cancer
(1)
(6)
Died** Without cancer With local/regional cancer With second primary cancer Cancer status unknown
– (3) – (2)
(8) (1) (1) (1)
Follow-up (range 44–122 months). Survival (range 1–111 months).
investigation of the effect of node level on survival involving 2058 patients with HNC, the 5-year survival rate was only 4% when level 4 nodal metastatic spread was documented.6 In a lymph node dissection report of 914 individuals with HNC at the Institut Gustave-Roussy, the 5-year survival rates were 38%, 25% and 5% when metastases were present in the upper, middle and lower jugular nodes, respectively.7 Such differing prognoses were also observed in other similar accounts of cervical metastases from an unknown primary site in the head and neck region.8,9 Our hypothesis to explain the dismal outcome seen in these individuals with HNC– LNNM stems from the fact that there are more frequent appearances of distant metastases whenever metastatic neoplasm is found in the lower jugular nodes of the neck.7,10 Furthermore, another proposition could be the occurrence of neoplastic spread to the mediastinal nodes. In a review of their elective superior mediastinal node dissection experience of 56 patients (42 with
Figure 2 Overall survival of 23 head and neck cancer patients with lower neck nodal metastases after intent to treat.
advanced laryngeal cancer and 14 with overt level 4 adenopathy), Oxford and Ducic11 detected occult mediastinal metastases in 27% of the evaluated people. The limitations of this study include its retrospective design, small sample size, variability of primary tumor sites and applied therapy, and the point that not all LNNMs were histologically confirmed and selection bias. These considerations certainly warrant cautious interpretation of the results and preclude a definite conclusion regarding best treatment. Nonetheless, this investigation is distinguished by its focus on the assessment of benefits obtained from an intent-to-treat management policy.
328
F.L. Ampil et al. / Oral Oncology 48 (2012) 325–328
In conclusion, this study suggests that the treatment of patients with HNC–LNNM needs to be aggressive. We believe in the adoption of an individualized management approach using a combination of treatment modes (i.e., preference for definitive surgery with postoperative radiotherapy/chemoradiation in cases of resectable lesions and chemoradiotherapy for unresectable disease) for this complicated neoplastic condition. Whether such combined therapy care truly has positive effects on survival deserves additional investigation. Conflict of interest statement None declared. References 1. Ampil FL, Datta R, Shockley W. Adjuvant postoperative external beam radiotherapy in head and neck cancer. J Oral Maxillofac Surg 1988;46:569–73. 2. Cho AH, Shah S, Ampil F, Bhartur S, Nathan CAO. N2 disease in patients with head and neck squamous cell cancer treated with chemoradiotherapy. Arch Otolaryngol Head Neck Surg 2009;135:1112–8.
3. Shah JP. Patterns of cervical lymph node metastasis for squamous cell carcinomas of the upper aerodigestive tract. Am J Surg 1990;160:405–9. 4. Colletier PJ, Garden AS, Morrison WH, Goepfert H, Geara F, Ang K. Postoperative radiotherapy for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site: outcomes and patterns of failure. Head Neck 1998;20:674–81. 5. Yalin Y, Pingzhang T, Smith GI, Ilankovan V. Management and outcome of cervical lymph node metastases of unknown primary sites: a retrospective study. Br J Oral Maxillofac Surg 2002;40:484–7. 6. Stell PM, Morton RP, Singh SD. Cervical lymph node metastases: the significance of the level of the lymph node. Clin Oncol 1983;9:101–7. 7. Mamelle G, Pampurik J, Luboinski B, Lancar R, Lusinchi A, Bosq J. Lymph node prognostic factors in head and neck squamous cell carcinomas. Am J Surg 1994;168:494–8. 8. Huang CC, Tseng FY, Yeh TH, Wen YH, Hsu CJ, Ko JY, et al. Prognostic factors of unknown primary head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg 2008;139:429–35. 9. Issing WJ, Taleban B, Tauber S. Diagnosis and management of carcinoma of unknown primary in the head and neck. Eur Arch Otorhinolaryngol 2003;260:436–43. 10. Shingaki S, Takada M, Sasai K, Bibi R, Kobayashi T, Nomura T, et al. Impact of lymph node metastasis on the pattern of failure and survival in oral carcinomas. Am J Surg 2003;185:278–84. 11. Oxford LE, Ducic Y. Elective transcervical superior mediastinal lymph node dissection for advanced laryngeal and level 4 N3 squamous cell carcinoma. Laryngoscope 2005;115:625–8.