Klinisch-pathologische Befunde, postoperative Überlebenszeiten und prognostische Faktoren bei Hunden mit primären Lungenkarzinomen

Zusammenfassung

Einleitung Primäre Karzinome der Lunge (PLK) beim Hund sind selten, ihre Behandlung erfolgt chirurgisch. Ziel dieser Studie war die Untersuchung klinisch-pathologischer Befunde, postoperativer medianer Überlebenszeiten (mÜZ) und prognostischer Faktoren.

Material und Methoden Retrospektive Auswertung von 61 Hunden mit 62 PLK, die zwischen 2007 und 2017 chirurgisch behandelt wurden. Die statistische Auswertung erfolgte mittels Kaplan-Meier und Logrank Methoden.

Ergebnisse Von 62 PLKs lagen 35 (56 %) peripher im Lungenlappen, 21 (34 %) hilusnah und 6 (10 %) betrafen den gesamten Lungenlappen. In 49 Fällen lagen differenzierte Adenokarzinome vor; niedrig differenzierte bzw. anaplastische Karzinome (n = 10) und Plattenepithelkarzinome (n = 2) waren deutlich seltener. Eine Prädisposition für bestimmte Lungenlappen war nicht nachzuweisen. Dreizehn (21 %) Patienten zeigten keine und 10 (16 %) nur unspezifische, nicht auf den Respirationstrakt hinweisende Symptome. Insgesamt zeigten 48 (79 %) Hunde klinische Symptome wie Husten, Dyspnoe, Lethargie, Gewichtsverlust, Leistungsschwäche, Erbrechen und/oder Fieber. Die tracheobronchialen Lymphknoten (TBLN) waren in 9 von 51 untersuchten Fällen histologisch positiv für Metastasierung (N1) und negativ (N0) in 42 Fällen (nicht untersucht n = 10). Daten zum Langzeitverlauf waren für 50 Patienten verfügbar. Prognostisch relevante Variablen waren Lymphknotenmetastasierung in die TBLN (mÜZ: N1 41 Tage, N0 570 Tage; p < 0,01), Lungenmetastasen (mÜZ: M1 125 Tage, M0 630 Tage; p < 0,01), histologischer Subtyp (mÜZ: differenzierte Karzinome 620 Tage; andere Karzinome 135 Tage; p < 0,01), Tumordurchmesser größer als 3 cm (mÜZ < 3 cm 1155 Tage, ≥ 3 cm 330 Tage; p = 0,02) und Tumorlokalisation (mÜZ: hilusnah 330 Tage, peripher 650 Tage; p = 0,04).

Schlussfolgerung Beim PLK sind TBLN Status, Organmetastasen, Tumorlokalisation, histologischer Subtyp und Tumorgröße prognostisch relevante Kriterien. Hunde ohne prognostisch negative Faktoren können lange Überlebenszeiten aufweisen. In mehr als einem Drittel der Fälle bleiben die Tumoren asymptomatisch (21 %) bzw. ohne respirationstraktspezifische (16 %) Symptome.

Abstract

Introduction Canine primary pulmonary carcinomas (PLC) are treated surgically. The goal of this study was to increase the veterinary database concerning clinical and pathological findings, postsurgical median survival times (mST), and prognostic factors in this tumor type.

Materials and methods Retrospective analysis of 61 dogs with 62 PLC treated surgically between 2007 and 2017. Survival analyses were performed using the Kaplan-Meier and Logrank methods.

Results Of the 62 tumors, 35 (56 %) were located peripherally in the lung, 21 (34 %) close to the hilus and 6 (10 %) affected the entire lobe. In 49 cases, differentiated (papillary or bronchoalveolar) adenocarcinomas were diagnosed; undifferentiated carcinomas or anaplastic carcinomas (n = 10) and squamous cell carcinomas (n = 2) were rare. There was no predisposition for specific lung lobes. Thirteen (21 %) of the patients exhibited no clinical signs, and 10 (16 %) displayed unspecific signs, unrelated to the respiratory tract. In total, forty-eight (79 %) dogs showed clinical signs such as coughing, dyspnea, lethargy, weight loss, exercise intolerance, vomiting and/or fever. Histologic examination of the tracheobronchial lymph nodes (TBLN), was positive for metastasis (N1) in 9 cases, negative (N0) in 42 patients, no TBLN histology was performed in 10 cases. Long-term follow-up information was available for 50 dogs. Variables with prognostic impact were presence of TBLN metastasis (mST: N1 41 days, N0 570 days; p < 0.01), lung metastases (mST: M1 125 days, M0 630 days; p < 0.01), histologic subtype (mST: tracheobronchial or papillary carcinoma 620 days; other carcinomas 135 days; p < 0.01); tumor diameter larger than 3 cm (mST < 3 cm 1155 days, ≥ 3 cm 330 days p = 0.02), and location of the tumor (mST: hilar 330 days, peripheral 650 days; p = 0.04).

Conclusion In PLK, TBLN status, M1, tumor location, histological subtype and tumor size are important, prognostically relevant factors; dogs without prognostically negative factors may have a good prognosis. More than one third of the dogs present asymptomatically (21 %) or without respiratory signs (16 %).

Schlüsselwörter

Kaniner Lungentumor - Karzinom der Lunge - Chirurgie - Prognose - Chemotherapie

Key words

Canine lung tumor - lung carcinoma - surgery - prognosis - chemotherapy

Publication History

Received: 29 July 2021

Accepted: 21 February 2022

Article published online:
02 November 2022

• Literatur

• 1 Dorn CR, Taylor DO, Frye FL. et al. Survey of animal neoplasms in Alameda and Contra Costa Counties, California. I. Methodology and description of cases. J Natl Cancer Inst 1968; 40: 295-305
• 2 Dobson JM, Samuel S, Milstein H. et al. Canine neoplasia in the UK: estimates of incidence rates from a population of insured dogs. J Small Anim Pract 2002; 43: 240-6
• 3 Hahn FF, Muggenburg BA, Griffith WC. Primary Lung Neoplasia in a Beagle Colony. Veterinary Pathology 1996; 33: 633-638
• 4 Ogilvie GK, Haschek WM, Withrow SJ. et al. Classification of primary lung tumors in dogs: 210 cases (1975–1985). J Am Vet Med Assoc 1989; 195: 106-108 (a)
• 5 Griffey SM, Kraegel SA, Madewell BR. Rapid detection of K-ras gene mutations in canine lung cancer using single-strand conformational polymorphism analysis. Carcinogenesis 1998; 19: 959-963
• 6 Wilson DW, Dungworth DL. Tumors of the respiratory tract. In Meuten DJ. Tumors in domestic animals. 4. Aufl.. Ames: Iowa State University Press; 2002: 365-399
• 7 Taylor R, Cumming R, Woodward A. et al. Passive smoking and lung cancer: a cumulative meta-analysis. Aust N Z J Public Health 2001; 25: 203-211
• 8 Reif JS, Dunn K, Ogilvie GK. et al. Passive smoking and canine lung cancer risk. Am J Epidemiol 1992; 135: 234-239
• 9 Bettini G, Morini M, Marconato L. et al. Association between environmental dust exposure and lung cancer in dogs. Vet J 2010; 186: 364-369
• 10 Sabattini S, Mancini FR, Marconato L. et al. EGFR overexpression in canine primary lung cancer: pathogenetic implications and impact on survival. Vet Comp Oncol 2014; 12: 237-248
• 11 Moulton JE, von Tscharner C, Schneider R. Classification of lung carcinomas in the dog and cat. Vet Pathol 1981; 18: 513-528
• 12 Cersosimo RJ. Lung cancer: A review. Am J Health Syst Pharm 2002; 59: 611-642
• 13 Abadie J, Hédan B, Cadieu E. et al. Epidemiology, pathology, and genetics of histiocytic sarcoma in the Bernese mountain dog breed. J Hered 2009; 100 (Suppl. 01) 19-27
• 14 Dobson J, Hoather T, McKinley TJ. et al. Mortality in a cohort of flat-coated retrievers in the UK. Vet Comp Oncol 2009; 7: 115-121
• 15 Shaiken LC, Evans SM, Goldschmidt MH. Radiographic findings in canine malignant histiocytosis. Vet Radiol 1991; 32: 237-242
• 16 Lenz JA, Furrow E, Craig LE. et al. Histiocytic sarcoma in 14 miniature schnauzers – a new breed predisposition?. J Small Anim Pract 2017; 58: 461-467
• 17 Marlowe KW, Robat CS, Clarke DM. et al. Primary pulmonary histiocytic sarcoma in dogs: A retrospective analysis of 37 cases (2000–2015). Vet Comp Oncol 2018; 16: 658-663
• 18 Ogilvie GK, Weigel RM, Haschek WM. et al. Prognostic factors for tumor remission and survival in dogs after surgery for primary lung tumor: 76 cases (1975–1985). J Am Vet Med Assoc 1989; 195: 109-112 (b)
• 19 Kessler M. Kleintieronkologie. 3. Aufl.. Stuttgart: Enke Verlag; 2013
• 20 McNiel EA, Ogilvie GK, Powers BE. et al. Evaluation of prognostic factors for dogs with primary lung tumors: 67 cases (1985–1992). J Am Vet Med Assoc 1997; 211: 1422-1427
• 21 Polton GA, Brearley MJ, Powell SM. et al. Impact of primary tumour stage on survival in dogs with solitary lung tumours. J Small Anim Pract 2008; 49: 66-71
• 22 Mehlhaff CJ, Leifer CE, Patnaik AK. et al. Surgical treatment of primary pulmonary neoplasia in 15 dogs. J Am Anim Hosp Assoc 1984; 20: 799-803
• 23 Lee BM, Clarke D, Watson M. et al. Retrospective evaluation of a modified human lung cancer stage classification in dogs with surgically excised primary pulmonary carcinomas. Vet Comp Oncol 2020; 18: 590-598
• 24 Owen LN. TNM Classification of tumors in domestic animals. 1st ed.. Genf: World Health Organisation, Geneva, Switzerland; 1980: 48-50
• 25 Paoloni MC, Adams WM, Dubielzig RR. et al. Comparison of results of computed tomography and radiography with histopathologic findings in tracheobronchial lymph nodes in dogs with primary lung tumors: 14 cases (1999–2002). J Am Vet Med Assoc 2006; 228: 1718-1722
• 26 Ballegeer EA, Adams WM, Dubielzig RR. et al. Computed tomography characteristics of canine tracheobronchial lymph node metastasis. Vet Radiol Ultrasound 2010; 51: 397-403
• 27 Rose RJ, Worley DR. A Contemporary Retrospective Study of Survival in Dogs With Primary Lung Tumors: 40 Cases (2005–2017). Front Vet Sci 2020; 7: 519703
• 28 Polton G, Finotello R, Sabattini S. et al. Survival analysis of dogs with advanced primary lung carcinoma treated by metronomic cyclophosphamide, piroxicam and thalidomide. Vet Comp Oncol 2018; 16: 399-408
• 29 Barrett LE, Pollard RE, Zwingenberger A. et al. Radiographic characterization of primary lung tumors in 74 dogs. Vet Radiol Ultrasound 2014; 55: 480-487
• 30 Culp WTN, Rebhun RB. Pulmonary neoplasia. In Vail DM, Tham DH, Liptak JM. Withrow & MacEwen’s Small Animal Clinical Oncology. 6. Aufl.. St.Louis: Elsevier; 2020: 507-523
• 31 Sharkey LC, Rosol TJ, Gröne A. et al. Production of granulocyte colony-stimulating factor and granulocyte-macrophage colony- stimulating factor by carcinomas in a dog and a cat with paraneoplastic leukocytosis. J Vet Intern Med 1996; 10: 405-408
• 32 Kojima K, Nakashima F, Boku A. et al. Clinicopathological study of involvement of granulocyte colony stimulating factor and granulocyte-macrophage colony stimulating factor in non-lymphohematopoietic malignant tumors accompanied by leukocytosis. Histol Histopathol 2002; 17: 1005-1016
• 33 Withers SS, Johnson EG, Culp WT. et al. Paraneoplastic hypertrophic osteopathy in 30 dogs. Vet Comp Oncol 2015; 13: 157-165
• 34 Skinner OT, Boston SE, Giglio RF. et al. Diagnostic accuracy of contrast-enhanced computed tomography for assessment of mandibular and medial retropharyngeal lymph node metastasis in dogs with oral and nasal cancer. Vet Comp Oncol 2018; 16: 562-570
• 35 Rahn H, Sadoul P, Farhi LE. et al. Distribution of ventilation and perfusion in the lobes of the dog’s lung in the supine and erect position. J Appl Physiol 1956; 8: 417-426
• 36 Maruyama H, Miura T, Sakai M. et al. The incidence of disseminated intravascular coagulation in dogs with malignant tumor. J Vet Med Sci 2004; 66: 573-575
• 37 Friedel G, Linder A, Pfeiffer S. et al. Radikalität lungenchirurgischer Eingriffe unter besonderer Berücksichtigung der Lymphadenektomie [Radical lung surgery interventions with special reference to lymphadenectomy]. Langenbecks Arch Chir Suppl Kongressbd 1996; 113: 785-789
• 38 Tuohy JL, Worley DR. Pulmonary lymph node charting in normal dogs with blue dye and scintigraphic lymphatic mapping. Res Vet Sci 2014; 97: 148-155
• 39 Meacci E, Margaritora S, Cesario A. et al. Surgical treatment of non-small cell lung cancer: mediastinal lymph node dissection. Rays 2004; 29: 423-429
• 40 Zhong W, Yang X, Bai J. et al. Complete mediastinal lymphadenectomy: the core component of the multidisciplinary therapy in resectable non-small cell lung cancer. Eur J Cardiothorac Surg 2008; 34: 187-195
• 41 Lababede O, Meziane MA. The Eighth Edition of TNM Staging of Lung Cancer: Reference Chart and Diagrams. Oncologist 2018; 23: 844-848
• 42 Kandathil A, Kay FU, Butt YM. et al. Role of FDG PET/CT in the Eighth Edition of TNM Staging of Non-Small Cell Lung Cancer. Radiographics 2018; 38: 2134-2149
• 43 Raptakis T, Boura P, Tsimpoukis S. et al. Endoscopic and endobronchial ultrasound-guided needle aspiration in the mediastinal staging of non-small cell lung cancer. Anticancer Res 2013; 33: 2369-2376
• 44 Sun WYL, Dang JT, Modasi A. et al. Diagnostic accuracy of sentinel lymph node biopsy using indocyanine green in lung cancer: a systematic review and meta-analysis. Gen Thorac Cardiovasc Surg 2020; 68: 905-913
• 45 Muhm JR, Miller WE, Fontana RS. et al. Lung cancer detected during a screening program using four-month chest radiographs. Radiology 1983; 148: 609-615
• 46 Poirier VJ, Burgess KE, Adams WM. et al. Toxicity, Dosage, and Efficacy of Vinorelbine (Navelbine) in dogs with spontaneous neoplasia. J Vet Intern Med 2004; 18: 536-539
• 47 Wouda RM, Miller ME, Chon E. et al. Clinical effects of vinorelbine administration in the management of various malignant tumor types in dogs: 58 cases (1997–2012). J Am Vet Med Assoc 2015; 246: 1230-1237
• 48 Martano M, Boston S, Morello E. et al Respiratory tract and thorax. In: Kudnig ST, Seguin B. Veterinary Surgical Oncology. Oxford: Wiley-Blackwell; 2012: 273-328