Sample Size Justification

Thesis: MRI Assessment of Depth of Invasion in Oral Tongue SCC - Correlation with Histopathology and Cervical Lymph Node Metastasis

Background and Prevalence (for Justification)

Sample Size Formula

Formula (Cochran, 1977 / WHO recommendation):

• n = minimum required sample size
• Z = Z-value for desired confidence level = 1.96 (for 95% confidence)
• p = expected proportion of cervical lymph node metastasis in oral tongue SCC = 0.60 (60%), based on Indian data from George et al. (2022) and Khunteta et al. (2022)
• q = 1 - p = 0.40
• d = allowable margin of error (absolute precision) = 0.14 (14%)

Calculation:

n = (1.96)² × 0.60 × 0.40
         ──────────────────
              (0.14)²

n = 3.8416 × 0.24
    ─────────────
       0.0196

n = 0.9220
    ───────
    0.0196

n = 47.04 ≈ 48

Alternatively, using a 5% margin of error (d = 0.05), n = ~369, which is impractical for a single-center retrospective/prospective study. For observational/imaging correlation studies in single institutions in India, the accepted convention is to use d = 0.14-0.15 to achieve a practical sample of 40-60, as demonstrated by multiple published Indian studies in this domain (Jayasankaran et al., 2022: n=45; Raut et al., 2024: n=30; George et al., 2022: n=70; Indian PMC study on OSCC tongue MRI DOI: n=33).

Alternate Formula: For Correlation Studies (Pearson's r)

• r = expected correlation coefficient = 0.85 (based on Lee & Choi meta-analysis 2023, pooled r = 0.86 for MRI-DOI vs histopathological DOI in OSCC)
• Z_α = 1.96 (two-tailed, α = 0.05)
• Z_β = 0.84 (power = 80%)

Fisher's Z (r=0.85): Zr = 0.5 × ln[(1+0.85)/(1-0.85)]
                       = 0.5 × ln[1.85/0.15]
                       = 0.5 × ln[12.33]
                       = 0.5 × 2.512
                       = 1.256

n = [(1.96 + 0.84) / 1.256]² + 3
  = [2.80 / 1.256]² + 3
  = [2.229]² + 3
  = 4.97 + 3
  = 7.97 ≈ 8 (minimum)

Final Justification Statement (Ready to Copy into Thesis)

Sample size justification: India has the highest burden of oral cavity cancer globally, with approximately 143,759 new cases in 2022 (GLOBOCAN, 2022). The oral tongue is the most common intraoral subsite, accounting for 41.9% of oral SCC in Indian patients. The proportion of cervical lymph node metastasis in oral tongue SCC in Indian tertiary centers is approximately 60% (George et al., Indian Journal of Cancer, 2022; Khunteta et al., South Asian Journal of Cancer, 2022).

Using the Cochran formula n = Z²pq/d², with Z = 1.96, p = 0.60, q = 0.40, and d = 0.14 (14% absolute precision), the minimum required sample size is n ≈ 48. Adding a 10% non-response buffer yields n ≈ 53. Considering institutional feasibility and comparison with published Indian single-center MRI-DOI studies (Jayasankaran et al., 2022: n=45; preliminary MRI-DOI study in OSCC tongue, PMC 2024: n=33), a sample of n = 50 patients is deemed adequate and pragmatically justified.

Furthermore, for the correlation objective (MRI-DOI vs histopathological DOI), using Fisher's Z transformation method with expected r = 0.85 (per Lee & Choi systematic review, Oral Oncology, 2023), the minimum sample at 80% power and α = 0.05 is only n = 8, confirming that 50 patients provides robust statistical power (>99%) for all planned analyses.

References (Numbered, for Thesis)

1. GLOBOCAN 2022 - India Fact Sheet. International Agency for Research on Cancer (IARC), WHO. Available: https://gco.iarc.who.int/media/globocan/factsheets/populations/356-india-fact-sheet.pdf
2. World Cancer Research Fund. Mouth and Oral Cancer Statistics, 2022. Available: https://www.wcrf.org/preventing-cancer/cancer-statistics/mouth-and-oral-cancer-statistics (India: 143,759 new cases; ASR 9.9/100,000 - #1 globally)
3. NAMS Task Force Report on Oral Cancer. Annals of National Academy of Medical Sciences (India). ~130,000 new oral cancer cases in India in 2020. Available: https://nams-annals.in/nams-task-force-report-on-oral-cancer
4. George R, Prakasan A, Anila KR, et al. Stage migration and treatment outcome in carcinoma tongue - A comparison of seventh and eighth AJCC pathological staging systems. Indian J Cancer. 2022 Oct-Dec;59(4). [PMID: 36861529] - (70 patients, Kerala; DOI-based staging; LN metastasis as prognostic factor)
5. Jayasankaran SC, Chelakkot PG, Suresh A, et al. Depth of Invasion in Squamous Cell Carcinoma of Buccal Mucosa: Is Magnetic Resonance Imaging a Good Predictor of Pathological Findings? Gulf J Oncol. 2022 May. [PMID: 35695345] - (Indian study, n=45; MRI DOI vs histopathology; Spearman's rho 0.693; p<0.001)
6. Raut T, Rath R, Das SN, et al. Evaluation of micrometastasis and isolated tumor cells in node-negative early-stage oral tongue squamous cell carcinoma: A cross-sectional study in tertiary-level hospitals in eastern India. Oral Surg Oral Med Oral Pathol Oral Radiol. 2024 Mar;137(3). [PMID: 38155003] - (Eastern India; n=30; DOI correlation with cervical nodal micrometastasis)
7. Khunteta N, Makkar A, Badwal JS, et al. Patterns of Neck Nodal Metastasis from Oral Cavity Carcinoma. South Asian J Cancer. 2022 Oct;11(4). [PMID: 36756101] - (Indian study, n=245; DOI as independent predictor of cervical LN metastasis)
8. Tumor thickness and depth of invasion in squamous cell carcinoma of tongue as indicators of loco-regional spread: A preliminary study. PMC11144744. 2024. - (Indian institution; n=33; MRI DOI vs histopathological DOI; correlation coefficient 0.82, p<0.05; cut-off DOI 7.02 mm for nodal metastasis)
9. Lee MK, Choi Y. Correlation between radiologic depth of invasion and pathologic depth of invasion in oral cavity squamous cell carcinoma: A systematic review and meta-analysis. Oral Oncol. 2023 Jan;136:106249. [PMID: 36417807] - (23 studies, n=1787; pooled r=0.86 for MRI; justifies expected correlation coefficient for sample size calculation)
10. Alharbi B, Alessa M, Alsayid H, et al. Magnetic resonance imaging accuracy in assessing depth of invasion in tongue squamous cell carcinomas and predicting cervical nodal metastasis. Eur Rev Med Pharmacol Sci. 2024 Mar;28(6):1783-1790. [PMID: 38497861] - (n=36; Pearson r=0.86; MRI-DOI cutoff 7.08 mm for nodal metastasis)
11. Cochran WG. Sampling Techniques. 3rd ed. New York: John Wiley & Sons; 1977. (Source formula for n = Z²pq/d²)

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