Sentinel lymph node biopsy for the diagnosis of lymph node involvement in oral/oropharyngeal squamous cell carcinoma
Appendices
Appendix 1. PubMed search strategy
#1 "Mouth Neoplasms"[Mesh]
#2 "Oropharyngeal Neoplasms"[Mesh]
#3 "Mouth Diseases"[Mesh]
#4 "Mouth"[Mesh]
#5 "Oropharynx"[Mesh]
#6 "Mouth Mucosa"[Mesh]
#7 "Cheek"[Mesh]
#8 oral [ti] OR oro* [ti] OR oris [ti] OR mouth [ti] OR tongue [ti] OR microglossia [ti] OR bucca* [ti] OR (head [ti] AND neck [ti]) OR ent [ti]
#9 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8
#10 ooscc
#11 #9 OR #10
#12 "Sentinel Lymph Node Biopsy" [Mesh]
#13 "Lymph Node Excision"[Mesh]
#14 "Lymph Nodes"[Mesh]
#15 lymph AND nod*
#16 #12 OR #13 OR #14 OR #15
#17 "Biopsy"[Mesh]
#18 biops*
#19 #17 OR #18
#20 #16 AND #19
#21 SLNB
#22 #20 OR #21
#23 #11 AND #22
Appendix 2. Assessment of methodological quality
Phase 1: State the review question
Phase 2: Flow diagram for the primary study
We will consider the flow diagram for each primary study or draw a diagram if a study has not reported or inadequately describes the patient flow. If required, we will give this information in the supplementary table/figure.
Phase 3: 'Risk of bias' and applicability judgements
Domain 1: Patient selection
A. Risk of bias
| Patient selection | Code | Description |
| Was a consecutive or random sample of patients enrolled? | Yes | If the method of recruitment is consecutive or random sample of eligible patients |
| No | If the method of recruitment is not consecutive or random sample of eligible patients | |
| Unclear | If there is insufficient information to make a judgement about the sampling method | |
| Was a case‐control design avoided?
| NA | Any study with case‐control design is not eligible for inclusion. |
| Did the study avoid inappropriate exclusions? | Yes | If the study has avoided inappropriate exclusions, such as excluding patients with non‐palpable nodes that are indeterminate on prior testing (imaging) |
| No | If the study has not avoided inappropriate exclusions, such as excluding patients with non‐palpable nodes that are indeterminate on prior testing (imaging) | |
| Unclear | If there is insufficient information to make a judgement about inappropriate exclusions |
Could the selection of patients have introduced bias?
| Low | If both the questions (1 and 3) are coded as 'yes' |
| High | If either of the questions (1 or 3) is coded as 'no' |
| Unclear | Any other possibility will be coded as 'unclear' |
B. Concerns regarding applicability
Is there concern that the included patients do not match the review question?
| Low | Patients without lymphadenopathy If > 90% of patients included are early stage (cT1/T2) |
| High | Patients with lymphadenopathy If > 10% of patients included are advanced stage (cT3/T4) |
| Unclear | No clear information on ‐ presence/absence of lymphadenopathy ‐ proportion of patients by stage (early versus advanced) |
Domain 2: Index test(s)
A. Risk of bias
Describe the index test and how it was conducted and interpreted:
A brief description of index test, its conduct and interpretation for each study will be reported.
| Index test | Code | Description |
| Were the index test results interpreted without knowledge of the results of the reference standard?
| Yes | If index test results were interpreted blind to the results of the reference test |
| No | If it is clear that index test result is interpreted with knowledge of the reference standard | |
| Unclear | If it is unclear whether blinding took place | |
| If a threshold was used, was it pre‐specified?
| NA | Threshold does not exist. |
Could the conduct or interpretation of the index test have introduced bias?
| Low | If at least two of the above are coded as 'yes' |
| High | If at least two of the above are coded as 'no' |
| Unclear | Any other possibility will be coded as 'unclear' |
B. Concerns regarding applicability
Is there concern that the index test, its conduct or interpretation differ from the review question?
| Low | Clear information on the conduct (any four points of (1) to (5) in the index test description) and interpretation (positive/negative/indeterminate) |
| High | Information only on any one of the five points (1) to (5) in the index test description for the conduct and no discrete interpretation (positive/negative/indeterminate) |
| Unclear | Insufficient information on the conduct and interpretation of the index test |
Domain 3: Reference standard
A. Risk of bias
Describe the reference standard and how it was conducted and interpreted:
A brief description of the reference standard, its conduct and interpretation for each study will be reported.
| Reference standard | Code | Description |
| Is the reference standard likely to classify the target condition? | Yes | The reference standard used met the pre‐stated criteria |
| No | The reference standard used did not meet the pre‐stated criteria | |
| Unclear | It is unclear exactly what reference standard was used | |
| Were the reference standard results interpreted without knowledge of the results of the index test?
| Yes | If the reference standard results were interpreted without the knowledge of index test results |
| No | If it is clear that the reference test was interpreted with knowledge of the index test | |
| Unclear | If it is unclear whether blinding took place |
Could the reference standard, its conduct or its interpretation have introduced bias?
| Low | If both are coded as 'yes' |
| High | If both are coded as 'no' |
| Unclear | Any other possibility will be coded as 'unclear' |
B. Concerns regarding applicability
Is there concern that the target condition as defined by the reference standard does not match the review question?
| Low | If assessment and reporting of the reference standard is as per the review protocol |
| High | If assessment and reporting of the reference standard is not as per the review protocol |
| Unclear | No clear information on the assessment and reporting of the reference standard |
Domain 4: Flow and timing
A. Risk of bias
Describe any patients who did not receive the index test(s) and/or reference standard or who were excluded from the 2 x 2 table (refer to flow diagram):
A description on withdrawals or loss to follow‐up, if any, for each study will be reported.
Describe the time interval and any interventions between the index test(s) and reference standard:
The time interval between the index test and reference standard will be documented for each study.
| Flow and timing | Code | Description |
| Was there an appropriate interval between the index test(s) and reference standard? | Yes | If the time period between the reference and index tests was immediate (on the same day) or within four weeks of the index test |
| No | If the time period was after four weeks of the index test | |
| Unclear | If the time period is not specified | |
| Did all patients receive a reference standard? | Yes | If neck dissection has been carried out for a majority (> 90%) of patients |
| No | If neck dissection has been carried out for < 90% of patients | |
| Unclear | No clear information about what per cent received the reference standard | |
| Did patients receive the same reference standard? | Yes | Majority (90%) of patients received the appropriate reference standard regardless of the index test |
| No | If < 90% received the appropriate reference standard regardless of the index test result | |
| Unclear | Insufficient information to assess whether all the patients received the appropriate reference standard | |
| Were all patients included in the analysis? | Yes | If all patients were included in the analysis |
| No | If all patients were not included and withdrawals were not explained | |
| Unclear | If all patients were not included and withdrawals were explained |
Could the patient flow have introduced bias?
| Low | If at least three of the above are coded as 'yes' |
| High | If at least three of the above are coded as 'no' |
| Unclear | Any other possibility will be coded as 'unclear' |
| T‐status | Characteristics | |
| TX | Primary tumour cannot be assessed | |
| T0 | No evidence of primary tumour | |
| Tis | Carcinoma in situ | |
| T1 | Tumour 2 cm or less in greatest dimension | |
| T2 | Tumour more than 2 cm but not more than 4 cm in greatest dimension | |
| T3 (oral cavity) T3 (oropharynx) | Tumour more than 4 cm in greatest dimension Tumour more than 4 cm in greatest dimension or involving lingual surface of epiglottis | |
| T4a Oral cavity Oropharynx | Moderately advanced local disease Tumour invades through cortical bone, into deep/extrinsic muscle of tongue (genioglossus, hyoglossus, palatoglossus and styloglossus), maxillary sinus or skin of face Tumour invades any of the following: larynx deep/extrinsic muscle of tongue (genioglossus, hyoglossus, palatoglossus and styloglossus), medial pterygoid, hard palate and mandible | |
| T4b
Oral cavity
Oropharynx | Very advanced local disease Tumour invades masticator space, pterygoid plates or skull base, or encases internal carotid artery Tumour invades any of the following: lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, skull base, or encases the carotid artery | |
| Note: superficial erosion alone of bone/tooth socket by gingival primary is not sufficient to classify a tumour as T4
| ||
| N‐status | Characteristics | |
| NX | Regional lymph nodes cannot be assessed | |
| N0 | No regional lymph node metastasis | |
| N1 | Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension | |
| N2
| Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension | |
| N2a. Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension | ||
| N2b. Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension | ||
| N2c | Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension | |
| N3 | Metastasis in a lymph node more than 6 cm in greatest dimension | |
| Note: midline nodes are considered ipsilateral nodes | ||
| M‐Status | ||
| M0 | No distant metastasis | |
| M1 | Distant metastasis | |
| OOSCC: oral and oropharyngeal squamous cell carcinoma | ||
| Stage 0 | Tis | N0 | M0 |
| Stage I | T1 | N0 | M0 |
| Stage II | T2 | N0 | M0 |
| Stage III | T1, T2 | N1 | M0 |
| T3 | N0, N1 | M0 | |
| Stage IVA | T1, T2, T3 | N2 | M0 |
| T4a | N0, N1, N2 | M0 | |
| Stage IVB | T4b | Any N | M0 |
| Any T | N3 | M0 | |
| Stage IVC | Any T | Any N | M1 |
