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Can the lymph node ratio predict outcome in head and neck cancer with single metastasis positive-node?
Oral Oncology 50 (2014) e18–e20
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Letter to the editor Can the lymph node ratio predict outcome in head and neck cancer with single metastasis positive-node? q
Introduction People with head and neck cancer (HNC) and a single histologically positive-node (PN1+) account for 12–34% of cases in reported studies [1–6]. The risk classification of patients with HNC–PN1+ is not clear perhaps because these individuals generally have a locoregional recurrent disease risk of less than 18% [5,7–9] and 5-year survival rates ranging from 70% to 81% [10,11]. Accurate risk stratification of patients with HNC–PN1+ is not possible at present, but may be influenced by the presence of other adverse histopathological features [12]. The lymph node ratio (LNR), ratio of the number of metastasis positive nodes to the total count of excised lymph nodes, has been proposed to circumvent the apparent inadequacy of a limited neck dissection and its consequent understaging effect. Recently, the LNR has been evaluated mostly for its prognostic relevance in oral carcinomas [4,6,13–16]. Our objective was to determine whether the LNR is useful in predicting locoregional recurrence (LRR) and prognosis in individuals with HNC–PN1+. Patients and methods This retrospective study was approved by the institutional review board. Thirty-four patients treated between 1976 and 2000, were selected for this clinical investigation because they met the following inclusion criteria: had a diagnosis of HNC–PN1+; underwent definitive surgery; had a minimum of 10 resected cervical lymph nodes and available post-treatment follow-up information. (neck dissection has been considered adequate when P10 cervical lymph nodes are excised [6]). Exclusion criteria included people with P2 histologically positive nodes; fewer than 10 excised neck nodes or in whom the total number of resected lymph nodes was not known, or who were lost to follow-up. All patients (eight women and 26 men with a median age of 56 years; age range, 38–85 years; seven (21%) were 65 years of age or older) were staged by clinical examination, imaging studies and histological confirmation according to the American Joint Committee on Cancer system. The total number of excised and examined nodes ranged from 10 to 75 nodes (median 22 nodes; mean 24 nodes). With a median LNR value of 5%, 16 people with a LNR finding of <5% were compared to 18 individuals with a LNR value of P5%.
q To be presented in part at the Multidisciplinary Symposium on Head and Neck Cancer, Phoenix, Arizona, February 20, 2014.
http://dx.doi.org/10.1016/j.oraloncology.2014.01.012 1368-8375/Ó 2014 Elsevier Ltd. All rights reserved.
Treatment Depending on the primary tumor site, definitive surgery consisted of composite resection for oral cavity (10 patients) or oropharyngeal cancers (7 patients) or total laryngectomy for larynx (15 patients) with thyroid lobectomy in four patients or hypopharynx (1 patient) cancers; one individual underwent salvage neck dissection for regional recurrent disease after prior primary surgery for a T3N0M0 oral tongue cancer. Neck dissection was unilateral in extent in 27 patients; bilateral neck dissection was performed for supraglottic laryngeal neoplasms or midline located tumors of the soft palate or floor of mouth in the remaining seven subjects. Following primary surgery, conventional fractionated external beam megavoltage irradiation was administered using a cobalt-60 or 6 MV linear accelerator treatment unit. The mean total dose to the primary tumor bed/upper neck was 59.4 Gy (range 50–70 Gy) and to the lower neck was 50.9 Gy (range 45–60 Gy). During the years of the study, the decision to administer postoperative radiotherapy (PORT) was highly individualized and made at the discretion of the radiation oncologist considering the absence of a formal institutional policy. PORT was applied based on the presence of additional adverse histopathological findings such as insecure/positive surgical margins (4 patients), poorly differentiated tumor (3 patients), perineural invasion (1 patient), nodal recurrent disease (1 patient), T3/4 primary neoplasms (11 patients) and on personal preference (4 patients). Ten people did not receive PORT due to the radiation oncologist’s judgment. Statistical analysis Cohort outcomes were in terms of locoregional recurrence, overall and disease-free survival rates. Survival rates were estimated using the Kaplan–Meier method and compared by the log-rank test. Cox proportional hazards regression analysis was used to examine independent significant factors that impact on overall and disease-free survival. Variables included in the model were age, primary tumor site and stage, the presence of other risk features, and the application of PORT. The LNR was analyzed as a continuous variable in the Cox model. All analyses were performed using the SAS software for statistical computing (SAS version 9.3, SAS Institute Inc., Cary, NC, USA). Results The subsites for the 10 individuals with oral cavity cancers were the oral tongue (4 patients), gingiva (3 patients), floor of mouth (2 patients), and lip (1 patient). In the seven people with oropharyngeal neoplasms, the subsite locations of the tumor were the soft palate (1 patient), tonsil (3 patients), and base of tongue
Letter to the editor / Oral Oncology 50 (2014) e18–e20 Table 1 Patient and treatment characteristics. Feature
Lymph node ratio
Median age in years Range P65 years Risk factors presenta Unilateral neck dissection Tumor stage T1–T2 T3–T4 Tumor siteb OC–OPX LYX–HPX Postoperative radiotherapy use
<5% (n = 16)
P5% (n = 18)
p-value
56 38–70 (3) 19% (10) 63% (12) 75%
55 46–85 (4) 22% (10) 56% (15) 83%
=0.68
(9) 56% (7) 44%
(11) 65% (6)* 35%
(8) 50% (8) 50% (12) 75%
(9)* 50% (8) 44% (12) 67%
>0.99 =0.46 =0.85 =0.62
=0.75
=0.72
a
Insecure/positive surgical margin, perineural invasion or poorly differentiated cancer, T3/T4 tumors, regional recurrence. b OC (oral cavity); OPX (oropharynx); LYX (larynx); HPX (hypopharynx). * One patient underwent salvage neck dissection for regional relapse of initially surgically treated T3N0M0 of the oral tongue.
e19
(95% CI: 6–33%). At the 10% level of significance, the disease-free survival rate associated with the P5% LNR value was higher than that for the LNR regard of <5%; the 3-year disease-free survival rates (Fig. 1) were 90% and 56% respectively (p < 0.10). Also, at the 7% significance level, the LRR rate for the P5% LNR value was lower than that for the <5% LNR account; the corresponding LRR rates were 6% (95% CI: 0–17%) and 36% (95% CI: 11–61%) p < 0.07. There was no observed advantage with the administration of PORT compared to surgery alone; the LRR rates were 18% (95% CI: 2–34%) and 22% (95% CI: 0–49%) respectively, p = 0.80 and the corresponding 3-year disease free survival rates were 69% and 75%, p = 0.99. Multivariate analysis of possible prognostic factors failed to identify an independent risk feature. Recurrent disease, histologically verified in six individuals, happened within 3 years of HNC diagnosis and treatment. The initial disease stage in these people was stage II (3 patients), stage III (2 patients) and stage IV (1 patient). Two individuals (both with regional disease relapse) did not receive PORT. In five (83%) of these subjects, the LNR value was <5%. All six patients died with disease and the median period of survival was 24.5 months (range, 11–27 months). Discussion
Figure 1. Disease-free survival with <5% and P5% lymph node ratios in head and neck cancer with single metastasis positive-node.
(3 patients). In the 15 people with laryngeal cancers, all of the tumors were situated in the supraglottic region; for the sole individual with the hypopharyngeal cancer, the neoplasm was from the pyriform sinus. In the remaining patient, the original HNC which recurred in the neck was located at the oral tongue. Table 1 summarizes the clinical and treatment information in the compared patient groups. There were no distinct dissimilarities between people with a LNR value of <5% and P5%. Overall, the 3-year survival rate was 41% with a median survival period of 24 months (95% confidence interval/95% CI: 21–27 months), and among the evaluable individuals, the LRR rate was 19%
The answer to our initial question is this: a low LNR value in HNC–PN1+ patients might indicate a dire outcome. In the present study, the observed median/mean number representing the total resected/examined cervical nodal count appears in line with that accepted minimum amount of >18 excised lymph nodes from the neck. An increase in nodal yield from the neck dissection has been associated with a greater chance of detecting nodal neoplastic invasion [17]. Moreover, the more metastases are found, so does the risk of recurrent disease rise [2,3,18] and the prognosis worsen [10,11]. The published literature (Table 2 [4,6,13,14]) has consistently demonstrated that a larger LNR value is associated with an adverse outcome. Although these retrospective studies were essentially not aimed at addressing the prognosis predictive value of the LNR specifically in HNC–PN1+ people, subgroup analysis revealed that the LNR could prove useful in determining the risk of failure [13], regional relapse [4] or survival [4,6,14] in individuals with HNC including those patients with PN1+ disease [4,6,13]. In contrast, the lower LNR value (one positive node/>22 nodes) in this cohort study was linked to a poorer patient outcome and difficult to explain adequately. The large variance in nodal yield from standard or modified neck dissection has undefined effects on the quality of life, cure rate, and survival. The number of lymph nodes in a person is not fixed and reflects, in part, the interaction between the tumor and host. It has been speculated that tumor necrosis usually connoting neoplasm aggressiveness, when sometimes observed, is a potent stimulator of lymph node hyperplasia leading to a detected rise in lymph node count. The constraints of this analysis are its retrospective design, the small number and mix of the studied population including the absence of a standard adjuvant treatment policy. We decided to
Table 2 Other studies examining the lymph node ratio (LNR) in head and neck cancer. Author
No. of patients
Gil et al. [13]
386 *
Kim et al. [14] Sayed et al. [4]* Urban et al. [6]*
*
211 1408 3091
Compared LNR values
Findings
6.06 vs >.06
Poorer 5-year disease-specific survival for patients with LNR > 0.06 vs LNR 6 0.06 (34% and 65% respectively) Poorer 5-year survival for patients with LNR > 0.06 vs LNR 6 0.06 (47% and 80% respectively) Poorer 5-year survival for patients with LNR > 0.09 vs LNR 6 0.09 (19% and 70% respectively) Median survival shortest for LNR > 0.13 vs LNR < 0.06 and LNR 0.06–0.13 (16 mos vs 32 mos and 25 mos respectively)
6.06 vs >.06 6.09 vs >.09 <.06 vs .06 .13 vs >.13
Median total number of positive nodes (2–3 nodes)/median total number of resected nodes (23–27 nodes) [4,6,14].
e20
Letter to the editor / Oral Oncology 50 (2014) e18–e20
report our finding of LRR (36%) and 3-year disease-free survival (56%) rates associated with a lower LNR value because on this basis, there could be a case for recommending PORT. Conventional wisdom advocates the use of adjuvant therapy when the relapse risk is >20% [19]. While the value of the LNR can only be suggested by our review of cases, the uncertain prognostic significance in HNC–PN1+ patients would seem underscored in this selected series. Conclusion It is important to ensure that staging is accurate so that locoregional tumor control and prognosis are not jeopardized by inadequate surgery or by the omission of adjuvant therapy based on misleading pathology. A useful application of the LNR is to improve upon the risk stratification of patients in whom this consideration is not clear. In this limited experience, the LNR was found to have an outcome predictive potential in patients with HNC–PN1+. A randomized study is required to resolve our posed question and establish best practice regarding the option of postoperative radiotherapy for this especial cohort of people. Funding None. Conflict of interest statement None of the authors of this study has financial or other relationships that may cause a conflict of interest. References [1] Bartelink H, Breuer K, Hart G, Annyas B, van Slooten E, Snow G. The value of postoperative radiotherapy as an adjuvant to radical neck dissection. Cancer 1983;52:1008–13. [2] DeSanto LW, Beahrs OH, Holt JJ, O’Fallon WM. Neck dissection: Is it worthwhile ? Laryngoscope 1982;92:502–9. [3] Medina JE, Byers RM. Supraomohyoid neck dissection: rationale, indications and surgical technique. Head Neck 1989;11:111–22. [4] Sayed SH, Sharma S, Rane P, Vaishampayan S, Talole S, Chaturvedi P, et al. Can metastatic lymph node ratio (LNR) predict survival in oral cavity cancer patients ? J Surg Oncol 2013;108:256–63. [5] Schmitz S, Machiels JP, Weynand B, Gregoire V, Hamoir M. Results of selective neck dissection in the primary management of head and neck squamous cell carcinoma. Eur Arch Otorhinlaryngol 2009;266:437–43. [6] Urban D, Gluck I, Pfeffer MR, Symon Z, Lawrence YR. Lymph node ratio predicts the benefit of post-operative radiotherapy in oral cavity cancer. Radiother Oncol 2013;106:74–9. [7] Cooper JS, Pajak TF, Forastiere A, Jacobs J, Fu KK, Ang KK, et al. Precisely defining high-risk operable head and neck tumors based on RTOG # 85–03 and # 88–24: targets for postoperative radiochemotherapy. Head Neck 1998;20:588–94.
[8] Lim YC, Choi EC. Surgery alone for squamous cell carcinoma of the oral cavity: survival rates, recurrence patterns, and salvage treatment. Acta Otolaryngol 2008;128:1132–7. [9] Peters LJ, Goepfert H, Ang KK, Byers RM, Maor MH, Guillamondegui O, et al. Evaluation of the dose for postoperative radiation therapy of head and neck cancer: first report of a prospective randomized trial. Internat J Radiat Oncol Biol 1993;26:3–11. [10] O’Brien CJ, Smith JW, Soong SJ, Urist MM, Maddox WA. Neck dissection with and without radiotherapy: prognostic factors, patterns of recurrence, and survival. Am J Surg 1986;152:456–63. [11] Shingaki S, Takada M, Sasai K, Bibi R, Kobayashi T, Nomura T, et al. Impact of lymph node metastasis on pattern of failure and survival in oral carcinomas. Am J Surg 2003;185:278–328. [12] Fan KH, Wang HM, Kang CJ, Lee LY, Huang SF, Lin CY, et al. Treatment results of postoperative radiotherapy on squamous cell carcinoma of the oral cavity: coexistence of multiple minor risk factors results in higher recurrence rates. Internat J Radiat Oncol Biol Phys 2010;77:1024–9. [13] Gil Z, Carlson DL, Boyle JO, Kraus DH, Shah JP, Shaha AR, et al. Lymph node density is a significant predictor of outcome in patients with oral cancer. Cancer 2009;115:5700–10. [14] Kim SY, Nam SY, Choi SH, Cho KJ, Roh JL. Prognostic value of lymph node density in node-positive patients with oral squamous cell carcinoma. Ann Surg Oncol 2011;18:2310–7. [15] Liao CT, Husueh C, Lee LY, Lin CY, Fan KH, Wang HM, et al. Dissection field and lymph node density predict prognosis in patients with oral cavity cancer and pathological node metastases treated with adjuvant therapy. Oral Oncol 2012;48:329–36. [16] Shrime MG, Bachar G, Lea J, Volling C, Ma C, Gullane PJ, et al. Nodal ratio as an independent predictor of survival in squamous cell carcinoma of the oral cavity. Head Neck 2009;31:1482–8. [17] Agrama MT, Reiter D, Cunnane MF, Topham AK, Keane WL. Nodal yield in neck dissection and the likelihood of metastases. Otolaryngol Head Neck Surg 2003;128:185–90. [18] Olsen KD, Caruso M, Foote RL, Stanley RJ, Lewis JE, Buskirk SJ, et al. Primary head and neck cancer. Histopathologic predictors of recurrence after neck dissection in patients with lymph node involvement. Arch Otolaryngol Head Neck Surg 1994;120:1370–4. [19] Weiss MH, Harrison LB, Isaacs RS. Use of decision analysis in planning a management strategy for the stage NO neck. Arch Otolaryngol Head Neck Surg 1994;120:699–702.
Federico L. Ampil Department of Radiology, University Health, USA Feist-Weiller Cancer Center, 1501 Kings Highway, Shreveport, LA 71130, USA Tel.: +1 318 675 5334; fax: +1 318 675 4697. E-mail address: [email protected] Gloria Caldito Department of Biometry, University Health, USA Feist-Weiller Cancer Center, Shreveport, LA 71130, USA Ghali E. Ghali Department of Oral Maxillofacial Surgery, University Health, USA Feist-Weiller Cancer Center, Shreveport, LA 71130, USA Available online 13 February 2014
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Letter to the editor Can the lymph node ratio predict outcome in head and neck cancer with single metastasis positive-node? q
Introduction People with head and neck cancer (HNC) and a single histologically positive-node (PN1+) account for 12–34% of cases in reported studies [1–6]. The risk classification of patients with HNC–PN1+ is not clear perhaps because these individuals generally have a locoregional recurrent disease risk of less than 18% [5,7–9] and 5-year survival rates ranging from 70% to 81% [10,11]. Accurate risk stratification of patients with HNC–PN1+ is not possible at present, but may be influenced by the presence of other adverse histopathological features [12]. The lymph node ratio (LNR), ratio of the number of metastasis positive nodes to the total count of excised lymph nodes, has been proposed to circumvent the apparent inadequacy of a limited neck dissection and its consequent understaging effect. Recently, the LNR has been evaluated mostly for its prognostic relevance in oral carcinomas [4,6,13–16]. Our objective was to determine whether the LNR is useful in predicting locoregional recurrence (LRR) and prognosis in individuals with HNC–PN1+. Patients and methods This retrospective study was approved by the institutional review board. Thirty-four patients treated between 1976 and 2000, were selected for this clinical investigation because they met the following inclusion criteria: had a diagnosis of HNC–PN1+; underwent definitive surgery; had a minimum of 10 resected cervical lymph nodes and available post-treatment follow-up information. (neck dissection has been considered adequate when P10 cervical lymph nodes are excised [6]). Exclusion criteria included people with P2 histologically positive nodes; fewer than 10 excised neck nodes or in whom the total number of resected lymph nodes was not known, or who were lost to follow-up. All patients (eight women and 26 men with a median age of 56 years; age range, 38–85 years; seven (21%) were 65 years of age or older) were staged by clinical examination, imaging studies and histological confirmation according to the American Joint Committee on Cancer system. The total number of excised and examined nodes ranged from 10 to 75 nodes (median 22 nodes; mean 24 nodes). With a median LNR value of 5%, 16 people with a LNR finding of <5% were compared to 18 individuals with a LNR value of P5%.
q To be presented in part at the Multidisciplinary Symposium on Head and Neck Cancer, Phoenix, Arizona, February 20, 2014.
http://dx.doi.org/10.1016/j.oraloncology.2014.01.012 1368-8375/Ó 2014 Elsevier Ltd. All rights reserved.
Treatment Depending on the primary tumor site, definitive surgery consisted of composite resection for oral cavity (10 patients) or oropharyngeal cancers (7 patients) or total laryngectomy for larynx (15 patients) with thyroid lobectomy in four patients or hypopharynx (1 patient) cancers; one individual underwent salvage neck dissection for regional recurrent disease after prior primary surgery for a T3N0M0 oral tongue cancer. Neck dissection was unilateral in extent in 27 patients; bilateral neck dissection was performed for supraglottic laryngeal neoplasms or midline located tumors of the soft palate or floor of mouth in the remaining seven subjects. Following primary surgery, conventional fractionated external beam megavoltage irradiation was administered using a cobalt-60 or 6 MV linear accelerator treatment unit. The mean total dose to the primary tumor bed/upper neck was 59.4 Gy (range 50–70 Gy) and to the lower neck was 50.9 Gy (range 45–60 Gy). During the years of the study, the decision to administer postoperative radiotherapy (PORT) was highly individualized and made at the discretion of the radiation oncologist considering the absence of a formal institutional policy. PORT was applied based on the presence of additional adverse histopathological findings such as insecure/positive surgical margins (4 patients), poorly differentiated tumor (3 patients), perineural invasion (1 patient), nodal recurrent disease (1 patient), T3/4 primary neoplasms (11 patients) and on personal preference (4 patients). Ten people did not receive PORT due to the radiation oncologist’s judgment. Statistical analysis Cohort outcomes were in terms of locoregional recurrence, overall and disease-free survival rates. Survival rates were estimated using the Kaplan–Meier method and compared by the log-rank test. Cox proportional hazards regression analysis was used to examine independent significant factors that impact on overall and disease-free survival. Variables included in the model were age, primary tumor site and stage, the presence of other risk features, and the application of PORT. The LNR was analyzed as a continuous variable in the Cox model. All analyses were performed using the SAS software for statistical computing (SAS version 9.3, SAS Institute Inc., Cary, NC, USA). Results The subsites for the 10 individuals with oral cavity cancers were the oral tongue (4 patients), gingiva (3 patients), floor of mouth (2 patients), and lip (1 patient). In the seven people with oropharyngeal neoplasms, the subsite locations of the tumor were the soft palate (1 patient), tonsil (3 patients), and base of tongue
Letter to the editor / Oral Oncology 50 (2014) e18–e20 Table 1 Patient and treatment characteristics. Feature
Lymph node ratio
Median age in years Range P65 years Risk factors presenta Unilateral neck dissection Tumor stage T1–T2 T3–T4 Tumor siteb OC–OPX LYX–HPX Postoperative radiotherapy use
<5% (n = 16)
P5% (n = 18)
p-value
56 38–70 (3) 19% (10) 63% (12) 75%
55 46–85 (4) 22% (10) 56% (15) 83%
=0.68
(9) 56% (7) 44%
(11) 65% (6)* 35%
(8) 50% (8) 50% (12) 75%
(9)* 50% (8) 44% (12) 67%
>0.99 =0.46 =0.85 =0.62
=0.75
=0.72
a
Insecure/positive surgical margin, perineural invasion or poorly differentiated cancer, T3/T4 tumors, regional recurrence. b OC (oral cavity); OPX (oropharynx); LYX (larynx); HPX (hypopharynx). * One patient underwent salvage neck dissection for regional relapse of initially surgically treated T3N0M0 of the oral tongue.
e19
(95% CI: 6–33%). At the 10% level of significance, the disease-free survival rate associated with the P5% LNR value was higher than that for the LNR regard of <5%; the 3-year disease-free survival rates (Fig. 1) were 90% and 56% respectively (p < 0.10). Also, at the 7% significance level, the LRR rate for the P5% LNR value was lower than that for the <5% LNR account; the corresponding LRR rates were 6% (95% CI: 0–17%) and 36% (95% CI: 11–61%) p < 0.07. There was no observed advantage with the administration of PORT compared to surgery alone; the LRR rates were 18% (95% CI: 2–34%) and 22% (95% CI: 0–49%) respectively, p = 0.80 and the corresponding 3-year disease free survival rates were 69% and 75%, p = 0.99. Multivariate analysis of possible prognostic factors failed to identify an independent risk feature. Recurrent disease, histologically verified in six individuals, happened within 3 years of HNC diagnosis and treatment. The initial disease stage in these people was stage II (3 patients), stage III (2 patients) and stage IV (1 patient). Two individuals (both with regional disease relapse) did not receive PORT. In five (83%) of these subjects, the LNR value was <5%. All six patients died with disease and the median period of survival was 24.5 months (range, 11–27 months). Discussion
Figure 1. Disease-free survival with <5% and P5% lymph node ratios in head and neck cancer with single metastasis positive-node.
(3 patients). In the 15 people with laryngeal cancers, all of the tumors were situated in the supraglottic region; for the sole individual with the hypopharyngeal cancer, the neoplasm was from the pyriform sinus. In the remaining patient, the original HNC which recurred in the neck was located at the oral tongue. Table 1 summarizes the clinical and treatment information in the compared patient groups. There were no distinct dissimilarities between people with a LNR value of <5% and P5%. Overall, the 3-year survival rate was 41% with a median survival period of 24 months (95% confidence interval/95% CI: 21–27 months), and among the evaluable individuals, the LRR rate was 19%
The answer to our initial question is this: a low LNR value in HNC–PN1+ patients might indicate a dire outcome. In the present study, the observed median/mean number representing the total resected/examined cervical nodal count appears in line with that accepted minimum amount of >18 excised lymph nodes from the neck. An increase in nodal yield from the neck dissection has been associated with a greater chance of detecting nodal neoplastic invasion [17]. Moreover, the more metastases are found, so does the risk of recurrent disease rise [2,3,18] and the prognosis worsen [10,11]. The published literature (Table 2 [4,6,13,14]) has consistently demonstrated that a larger LNR value is associated with an adverse outcome. Although these retrospective studies were essentially not aimed at addressing the prognosis predictive value of the LNR specifically in HNC–PN1+ people, subgroup analysis revealed that the LNR could prove useful in determining the risk of failure [13], regional relapse [4] or survival [4,6,14] in individuals with HNC including those patients with PN1+ disease [4,6,13]. In contrast, the lower LNR value (one positive node/>22 nodes) in this cohort study was linked to a poorer patient outcome and difficult to explain adequately. The large variance in nodal yield from standard or modified neck dissection has undefined effects on the quality of life, cure rate, and survival. The number of lymph nodes in a person is not fixed and reflects, in part, the interaction between the tumor and host. It has been speculated that tumor necrosis usually connoting neoplasm aggressiveness, when sometimes observed, is a potent stimulator of lymph node hyperplasia leading to a detected rise in lymph node count. The constraints of this analysis are its retrospective design, the small number and mix of the studied population including the absence of a standard adjuvant treatment policy. We decided to
Table 2 Other studies examining the lymph node ratio (LNR) in head and neck cancer. Author
No. of patients
Gil et al. [13]
386 *
Kim et al. [14] Sayed et al. [4]* Urban et al. [6]*
*
211 1408 3091
Compared LNR values
Findings
6.06 vs >.06
Poorer 5-year disease-specific survival for patients with LNR > 0.06 vs LNR 6 0.06 (34% and 65% respectively) Poorer 5-year survival for patients with LNR > 0.06 vs LNR 6 0.06 (47% and 80% respectively) Poorer 5-year survival for patients with LNR > 0.09 vs LNR 6 0.09 (19% and 70% respectively) Median survival shortest for LNR > 0.13 vs LNR < 0.06 and LNR 0.06–0.13 (16 mos vs 32 mos and 25 mos respectively)
6.06 vs >.06 6.09 vs >.09 <.06 vs .06 .13 vs >.13
Median total number of positive nodes (2–3 nodes)/median total number of resected nodes (23–27 nodes) [4,6,14].
e20
Letter to the editor / Oral Oncology 50 (2014) e18–e20
report our finding of LRR (36%) and 3-year disease-free survival (56%) rates associated with a lower LNR value because on this basis, there could be a case for recommending PORT. Conventional wisdom advocates the use of adjuvant therapy when the relapse risk is >20% [19]. While the value of the LNR can only be suggested by our review of cases, the uncertain prognostic significance in HNC–PN1+ patients would seem underscored in this selected series. Conclusion It is important to ensure that staging is accurate so that locoregional tumor control and prognosis are not jeopardized by inadequate surgery or by the omission of adjuvant therapy based on misleading pathology. A useful application of the LNR is to improve upon the risk stratification of patients in whom this consideration is not clear. In this limited experience, the LNR was found to have an outcome predictive potential in patients with HNC–PN1+. A randomized study is required to resolve our posed question and establish best practice regarding the option of postoperative radiotherapy for this especial cohort of people. Funding None. Conflict of interest statement None of the authors of this study has financial or other relationships that may cause a conflict of interest. References [1] Bartelink H, Breuer K, Hart G, Annyas B, van Slooten E, Snow G. The value of postoperative radiotherapy as an adjuvant to radical neck dissection. Cancer 1983;52:1008–13. [2] DeSanto LW, Beahrs OH, Holt JJ, O’Fallon WM. Neck dissection: Is it worthwhile ? Laryngoscope 1982;92:502–9. [3] Medina JE, Byers RM. Supraomohyoid neck dissection: rationale, indications and surgical technique. Head Neck 1989;11:111–22. [4] Sayed SH, Sharma S, Rane P, Vaishampayan S, Talole S, Chaturvedi P, et al. Can metastatic lymph node ratio (LNR) predict survival in oral cavity cancer patients ? J Surg Oncol 2013;108:256–63. [5] Schmitz S, Machiels JP, Weynand B, Gregoire V, Hamoir M. Results of selective neck dissection in the primary management of head and neck squamous cell carcinoma. Eur Arch Otorhinlaryngol 2009;266:437–43. [6] Urban D, Gluck I, Pfeffer MR, Symon Z, Lawrence YR. Lymph node ratio predicts the benefit of post-operative radiotherapy in oral cavity cancer. Radiother Oncol 2013;106:74–9. [7] Cooper JS, Pajak TF, Forastiere A, Jacobs J, Fu KK, Ang KK, et al. Precisely defining high-risk operable head and neck tumors based on RTOG # 85–03 and # 88–24: targets for postoperative radiochemotherapy. Head Neck 1998;20:588–94.
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Federico L. Ampil Department of Radiology, University Health, USA Feist-Weiller Cancer Center, 1501 Kings Highway, Shreveport, LA 71130, USA Tel.: +1 318 675 5334; fax: +1 318 675 4697. E-mail address: [email protected] Gloria Caldito Department of Biometry, University Health, USA Feist-Weiller Cancer Center, Shreveport, LA 71130, USA Ghali E. Ghali Department of Oral Maxillofacial Surgery, University Health, USA Feist-Weiller Cancer Center, Shreveport, LA 71130, USA Available online 13 February 2014