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LARENKS SKUAMÖZ HÜCRELİ KARSİNOMLU HASTALARDA KLİNİK VE HİSTOPATOLOJİK PARAMETRELERİN SAĞKALIM ÜZERİNDEKİ ETKİSİNİN İNCELENMESİ

INVESTIGATION OF THE EFFECT OF CLINICAL AND HISTOPATHOLOGICAL PARAMETERS ON SURVIVAL IN PATIENTS WITH LARYNGEAL SQUAMOUS CELL CARCINOMA

  1. Tez No: 1017077
  2. Yazar: EMRE İPEK
  3. Danışmanlar: PROF. DR. ABDÜLKADİR İMRE
  4. Tez Türü: Tıpta Uzmanlık
  5. Konular: Kulak Burun ve Boğaz, Otorhinolaryngology (Ear-Nose-Throat)
  6. Anahtar Kelimeler: Larenks kanseri, skuamöz hücreli karsinom, ekstranodal yayılım, lenfovasküler invazyon, WPOI, hastalıksız sağkalım, Laryngeal cancer, squamous cell carcinoma, extranodal extension, lymphovascular invasion, WPOI, disease-free survival
  7. Yıl: 2026
  8. Dil: Türkçe
  9. Üniversite: İzmir Katip Çelebi Üniversitesi
  10. Enstitü: İzmir Atatürk Eğitim ve Araştırma Hastanesi
  11. Ana Bilim Dalı: Kulak Burun Boğaz Hastalıkları Ana Bilim Dalı
  12. Bilim Dalı: Belirtilmemiş.
  13. Sayfa Sayısı: Belirtilmemiş.

Özet

ÖZET LARENKS SKUAMÖZ HÜCRELİ KARSİNOMLU HASTALARDA KLİNİK VE HİSTOPATOLOJİK PARAMETRELERİN SAĞKALIM ÜZERİNDEKİ ETKİSİNİN İNCELENMESİ Emre İPEK İzmir Kâtip Çelebi Üniversitesi Tıp Fakültesi Atatürk Eğitim ve Araştırma Hastanesi Kulak Burun ve Boğaz Hastalıkları Anabilim Dalı Uzmanlık Tezi, İzmir, Türkiye, 2026 Amaç: Larenks skuamöz hücreli karsinomunda prognoz, yalnızca TNM evresiyle değil primer tümöre ait histopatolojik özellikler ve servikal nodal hastalığın nicel/nitel parametreleriyle de ilişkilidir. Bu çalışmada, cerrahi tedavi ve boyun diseksiyonu uygulanan larenks skuamöz hücreli karsinomlu hastalarda klinik ve histopatolojik değişkenlerin genel sağkalım, hastalıksız sağkalım, hastalığa özgü sağkalım, servikal nodal metastaz, klinik N0 hastalardaki okült nodal metastaz ve ekstranodal yayılım ile ilişkilerinin değerlendirilmesi amaçlandı. Yöntem: Bu tek merkezli retrospektif çalışmaya, 2015–2025 yılları arasında larenks skuamöz hücreli karsinomu nedeniyle cerrahi tedavi ve boyun diseksiyonu uygulanan 103 hasta dâhil edildi. Demografik veriler, tümör lokalizasyonu, klinik ve patolojik TNM evresi, tümör boyutu, invazyon derinliği, subglottik uzanım, anterior komissür tutulumu, tiroid kartilaj invazyonu, cerrahi sınır, perinöral invazyon, lenfovasküler invazyon, diferansiyasyon derecesi, en kötü invazyon paterni, tümör tomurcuklanması, tümörü infiltre eden lenfosit yanıtı, metastatik lenf nodu sayısı, lenf nodu oranı ve ekstranodal yayılım değerlendirildi. Sağkalım analizlerinde Kaplan–Meier yöntemi ve Cox regresyon modelleri; patolojik servikal nodal metastaz, klinik N0 hastalardaki okült nodal metastaz ve pN-pozitif hastalardaki ekstranodal yayılım analizlerinde Firth lojistik regresyonu kullanıldı. İkili ve üçlü özellik kombinasyonlarının analizinde, çok sayıda karşılaştırmadan kaynaklanabilecek yanlış pozitiflik riski Benjamini–Hochberg FDR düzeltmesiyle kontrol edildi. Bulgular: Hastaların 98'i erkek, 5'i kadındı; ortalama yaş 62,30 ± 8,22 yıl idi. Servikal nodal metastaz 41 hastada, ekstranodal yayılım 20 hastada saptandı; ekstranodal yayılım pN-pozitif hastaların 20/41'inde mevcuttu. WPOI 4–5 toplam 56 hastada izlendi. Ters Kaplan–Meier yöntemiyle medyan takip süresi 60 ay olup vii izlemde 34 genel sağkalım olayı, 23 hastalıksız sağkalım olayı ve 15 hastalığa özgü ölüm görüldü. Beş yıllık genel sağkalım, hastalıksız sağkalım ve hastalığa özgü sağkalım sırasıyla %64,8, %75,2 ve %82,6 idi. Çok değişkenli modellerde genel sağkalım için ileri pT ve lenfovasküler invazyon; hastalıksız sağkalım için tümör boyutu ve ekstranodal yayılım bağımsız prognostik değişkenler olarak saptandı. Primer tümör spesmeninde servikal nodal metastazla en güçlü ilişkiyi lenfovasküler invazyon ve invazyon derinliği gösterdi. Klinik N0 olan 71 hastanın 14'ünde (%19,7) okült servikal nodal metastaz saptandı. Klinik N0 alt grupta LVI okült nodal metastaz ile güçlü ve bağımsız ilişkiliydi (düzeltilmiş OR=14,89; %95 GA: 3,30–67,13; p=0,0004). DOI'nin her 5 mm artışı tek değişkenli analizde okült metastaz olasılığıyla ilişkili bulunurken (OR=1,49; %95 GA: 1,01–2,18; p=0,0424), LVI ile kurulan modelde etkisi sınırda kaldı (p=0,0860). pN-pozitif hastalarda WPOI 4–5 ile ekstranodal yayılım arasında güçlü ve lenf nodu oranından bağımsız bir ilişki bulundu. WPOI 5 ve yüksek tümör tomurcuklanması hastalığa özgü sağkalımla ilişkili bulundu; ancak olay sayısının sınırlı olması nedeniyle bu sonuçlar ön bulgu olarak değerlendirildi. Sonuçlar: Primer tümöre ve boyun diseksiyonuna ait histopatolojik bulguların TNM evresiyle birlikte değerlendirilmesi, hastaların prognostik sınıflandırılmasına ek bilgi sağlayabilir. Lenfovasküler invazyon ve invazyon derinliği, servikal nodal metastazla en güçlü ilişkiyi gösteren primer tümör bulgularıydı. Lenfovasküler invazyon, klinik N0 hastalarda okült nodal metastazla güçlü ve bağımsız olarak ilişkili bulundu. Tümör boyutu ve ekstranodal yayılım hastalıksız sağkalımla; ileri pT kategorisi ve lenfovasküler invazyon ise genel sağkalımla bağımsız olarak ilişkiliydi. WPOI 4–5 ile ekstranodal yayılım arasındaki ilişki, primer tümörün invazyon sınırındaki büyüme biçimi ile metastatik lenf nodunda kapsül dışına yayılım arasında bir bağlantı bulunabileceğini göstermektedir. Bu ilişkinin daha geniş ve bağımsız hasta serilerinde doğrulanması önemlidir.

Özet (Çeviri)

ABSTRACT INVESTIGATION OF THE EFFECT OF CLINICAL AND HISTOPATHOLOGICAL PARAMETERS ON SURVIVAL IN PATIENTS WITH LARYNGEAL SQUAMOUS CELL CARCINOMA Emre İPEK Izmir Katip Celebi University Faculty of Medicine, Izmir Ataturk Training and Research Hospital, Department of Otorhinolaryngology, Medical Specialization Thesis, Izmir, Türkiye, 2026 Aim: The prognosis of laryngeal squamous cell carcinoma is associated not only with TNM stage but also with histopathological features of the primary tumor and quantitative and qualitative parameters of cervical nodal disease. This study aimed to evaluate the associations of clinical and histopathological variables with overall survival, disease-free survival, disease-specific survival, cervical nodal metastasis, occult nodal metastasis in clinically node-negative patients, and extranodal extension in patients with laryngeal squamous cell carcinoma who underwent surgical treatment and neck dissection. Methods: This single-center retrospective study included 103 patients who underwent surgical treatment and neck dissection for laryngeal squamous cell carcinoma between 2015 and 2025. Demographic data, tumor localization, clinical and pathological TNM stage, tumor size, depth of invasion, subglottic extension, anterior commissure involvement, thyroid cartilage invasion, surgical margin status, perineural invasion, lymphovascular invasion, histological differentiation, worst pattern of invasion, tumor budding, tumor-infiltrating lymphocyte response, number of metastatic lymph nodes, lymph node ratio, and extranodal extension were evaluated. Kaplan–Meier analysis and Cox regression models were used for survival outcomes, whereas Firth logistic regression was used for pathological cervical nodal metastasis, occult nodal metastasis in clinically node-negative patients, and extranodal extension in the pN-positive subgroup. The false discovery rate arising from the analysis of two- and three-feature combinations was controlled using the Benjamini–Hochberg procedure. Results: Of the 103 patients, 98 were male and 5 were female; the mean age was 62.30 ± 8.22 years. Cervical nodal metastasis was detected in 41 patients, and ix extranodal extension was observed in 20 patients; extranodal extension was present in 20 of 41 pN-positive patients. WPOI 4–5 was identified in 56 patients. The median follow-up calculated by reverse Kaplan–Meier analysis was 60 months. During follow-up, 34 overall survival events, 23 disease-free survival events, and 15 disease-specific deaths occurred. The 5-year overall survival, disease-free survival, and disease-specific survival rates were 64.8%, 75.2%, and 82.6%, respectively. In multivariable models, advanced pT stage and lymphovascular invasion were independent prognostic variables for overall survival, whereas tumor size and extranodal extension were independent prognostic variables for disease-free survival. The strongest primary specimen predictors of cervical nodal metastasis were lymphovascular invasion and depth of invasion. Occult cervical nodal metastasis was identified in 14 of 71 clinically node-negative patients (19.7%). In the cN0 subgroup, lymphovascular invasion was strongly and independently associated with occult nodal metastasis (adjusted OR=14.89; 95% CI: 3.30–67.13; p=0.0004). Each 5-mm increase in depth of invasion was associated with occult metastasis in univariable analysis (OR=1.49; 95% CI: 1.01–2.18; p=0.0424), whereas its contribution was attenuated after adjustment for lymphovascular invasion (p=0.0860). In pN-positive patients, WPOI 4–5 showed a strong association with extranodal extension independent of lymph node ratio. Although WPOI 5 and high tumor budding were associated with disease-specific survival, these results were regarded as preliminary because of the limited number of events. Conclusion: In laryngeal squamous cell carcinoma, evaluating histopathological findings of the primary tumor and neck dissection together with TNM stage may provide additional prognostic information. Lymphovascular invasion and depth of invasion showed the strongest associations with cervical nodal metastasis, and lymphovascular invasion was strongly and independently associated with occult nodal metastasis in clinically node-negative patients. Tumor size and extranodal extension were independently associated with disease-free survival, whereas advanced pT category and lymphovascular invasion were independently associated with overall survival. The association between WPOI 4–5 and extranodal extension suggests a possible relationship between the growth pattern at the invasive boundary of the primary tumor and spread beyond the lymph-node capsule. This relationship should be reassessed in larger independent cohorts. ABSTRACT INVESTIGATION OF THE EFFECT OF CLINICAL AND HISTOPATHOLOGICAL PARAMETERS ON SURVIVAL IN PATIENTS WITH LARYNGEAL SQUAMOUS CELL CARCINOMA Emre İPEK Izmir Katip Celebi University Faculty of Medicine, Izmir Ataturk Training and Research Hospital, Department of Otorhinolaryngology, Medical Specialization Thesis, Izmir, Türkiye, 2026 Aim: The prognosis of laryngeal squamous cell carcinoma is associated not only with TNM stage but also with histopathological features of the primary tumor and quantitative and qualitative parameters of cervical nodal disease. This study aimed to evaluate the associations of clinical and histopathological variables with overall survival, disease-free survival, disease-specific survival, cervical nodal metastasis, occult nodal metastasis in clinically node-negative patients, and extranodal extension in patients with laryngeal squamous cell carcinoma who underwent surgical treatment and neck dissection. Methods: This single-center retrospective study included 103 patients who underwent surgical treatment and neck dissection for laryngeal squamous cell carcinoma between 2015 and 2025. Demographic data, tumor localization, clinical and pathological TNM stage, tumor size, depth of invasion, subglottic extension, anterior commissure involvement, thyroid cartilage invasion, surgical margin status, perineural invasion, lymphovascular invasion, histological differentiation, worst pattern of invasion, tumor budding, tumor-infiltrating lymphocyte response, number of metastatic lymph nodes, lymph node ratio, and extranodal extension were evaluated. Kaplan–Meier analysis and Cox regression models were used for survival outcomes, whereas Firth logistic regression was used for pathological cervical nodal metastasis, occult nodal metastasis in clinically node-negative patients, and extranodal extension in the pN-positive subgroup. The false discovery rate arising from the analysis of two- and three-feature combinations was controlled using the Benjamini–Hochberg procedure. Results: Of the 103 patients, 98 were male and 5 were female; the mean age was 62.30 ± 8.22 years. Cervical nodal metastasis was detected in 41 patients, and ix extranodal extension was observed in 20 patients; extranodal extension was present in 20 of 41 pN-positive patients. WPOI 4–5 was identified in 56 patients. The median follow-up calculated by reverse Kaplan–Meier analysis was 60 months. During follow-up, 34 overall survival events, 23 disease-free survival events, and 15 disease-specific deaths occurred. The 5-year overall survival, disease-free survival, and disease-specific survival rates were 64.8%, 75.2%, and 82.6%, respectively. In multivariable models, advanced pT stage and lymphovascular invasion were independent prognostic variables for overall survival, whereas tumor size and extranodal extension were independent prognostic variables for disease-free survival. The strongest primary specimen predictors of cervical nodal metastasis were lymphovascular invasion and depth of invasion. Occult cervical nodal metastasis was identified in 14 of 71 clinically node-negative patients (19.7%). In the cN0 subgroup, lymphovascular invasion was strongly and independently associated with occult nodal metastasis (adjusted OR=14.89; 95% CI: 3.30–67.13; p=0.0004). Each 5-mm increase in depth of invasion was associated with occult metastasis in univariable analysis (OR=1.49; 95% CI: 1.01–2.18; p=0.0424), whereas its contribution was attenuated after adjustment for lymphovascular invasion (p=0.0860). In pN-positive patients, WPOI 4–5 showed a strong association with extranodal extension independent of lymph node ratio. Although WPOI 5 and high tumor budding were associated with disease-specific survival, these results were regarded as preliminary because of the limited number of events. Conclusion: In laryngeal squamous cell carcinoma, evaluating histopathological findings of the primary tumor and neck dissection together with TNM stage may provide additional prognostic information. Lymphovascular invasion and depth of invasion showed the strongest associations with cervical nodal metastasis, and lymphovascular invasion was strongly and independently associated with occult nodal metastasis in clinically node-negative patients. Tumor size and extranodal extension were independently associated with disease-free survival, whereas advanced pT category and lymphovascular invasion were independently associated with overall survival. The association between WPOI 4–5 and extranodal extension suggests a possible relationship between the growth pattern at the invasive boundary of the primary tumor and spread beyond the lymph-node capsule. This relationship should be reassessed in larger independent cohorts.

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