AMMVEPE 1968 - 2015
MEMORIAS DE LAS PONENCIAS EN EL CURSO DE ACTUALIZACIÓN EN ONCOLOGÍA MÉDICA Y QUIRÚRGICA MÉXICO, D. F. AGOSTO 26, 27 y 28 DE 2015
Asociación Mexicana de Médicos Veterinarios Especialistas en Pequeñas Especies, S. C. www.ammvepe.com.mx
PONENCIAS DEL CURSO DE ACTUALIZACIÓN EN ONCOLOGÍA MÉDICA Y QUIRÚRGICA AMMVEPE Agosto 26, 27 y 28 de 2015 ABORDAJE DEL PACIENTE CON CARCINOMA DE CÉLULAS ESCAMOSAS MVZ MMVZ Angelina Gutiérrez Barroso ACTUALIZACIONES EN EL TRATAMIENTO DE MASTOCITOMA CANINO MVZ MMVZ Angelina Gutiérrez Barroso CONSIDERACIONES EN EL PACIENTE ONCOLÓGICO MVZ MMVZ Angelina Gutiérrez Barroso DIAGNOSIS AND PROGNOSIS OF CANINE OSTEOSARCOMA DVM, MS Bernard Séguin FELINE AND CANINE THYROID TUMORS DVM, MS Bernard Séguin INDICATIONS AND OUTCOME FOR PULMONARY METASTASECTOMY DVM, MS Bernard Séguin
LINFOMA CANINO Y FELINO: TOMA DE DECISIONES MVZ MMVZ Angelina Gutiérrez Barroso LYMPHOLOGY AND SENTINEL LYMPH NODE MAPPING DVM, DACVS-SA Deanna R. Worley MELANOMA MVZ MMVZ Angelina Gutiérrez Barroso ORAL AND INTESTINAL TUMORS IN DOGS AND CATS DVM, DACVS-SA Deanna R. Worley ORBITECTOMIES DVM, DACVS-SA Deanna R. Worley PERIANAL TUMORS DVM, DACVS-SA Deanna R. Worley QUIMIOTERAPIA EN TUMORES MAMARIOS: CUÁNDO Y CUÁL? MVZ MMVZ Angelina Gutiérrez Barroso QUIMIOTERAPIA PALIATIVA Y METRONÓMICA EN PERROS Y GATOS: USOS Y ABUSOS MVZ MMVZ Angelina Gutíerrez Barroso RESPIRATOY NEOPLASIA DVM, DACVS-SA Deanna R. Worley
SOFT TISSUE SARCOMAS & HEMANGIOSARCOMAS DVM, DACVS-SA Deanna R. Worley SURGEON’S APPROACH TO ADRENAL TUMORS DVM, MS Bernard Séguin SURGEON’S APPROACH TO PRIMARY HYPERPARATHYROIDISM DVM, MS Bernard Séguin SURGICAL ONCOLOGY CASE ROUNDS DVM, DACVS-SA Deanna R. Worley THORACIC AND CARDIOVASCULAR SURGERY: ONCOLOGY DVM, DACVS-SA Deanna R. Worley TIPS AND TRICKS TO PERFORMING A BIOPSY DVM, MS Bernard Séguin TIPS AND TRICKS TO REMOVING A TUMOR DVM, MS Bernard Séguin TREATING APPENDICULAR OSTEOSARCOMA IN DOGS DVM, MS Bernard Séguin
SURGICAL ONCOLOGY CASE ROUNDS Deanna R. Worley, DVM, DACVS-SA ACVS Founding Fellow, Surgical Oncology Associate Professor, Surgical Oncology dworley@colostate.edu
Lola • • • •
10 YO FS Weimaraner Bladder TCC 2 yrs Bladder IMRT Mitoxantrone
Lola • • • • •
Nephrectomy 1 yr ago Vinblastine Regional LN mets Carboplatin “Polyarthropathy”
Lola • Pulmonary metastasis & Hypertrophic Osteopathy • Sternal & periarotic lymphandenopathy • Urethral stricture • Urethral stent placement • Gemcitabine
Corey • • • • • •
4YO FS Airedale Terrier OSA right femur 2 yrs ago Amp Carboplatin, Gemzar, doxorubicin Acute trembling, collapse, fatigue Intracardiac mass
Annie • • • • •
10 YO FS German Wirehaired Pointer LSA CR 6mo later PD Recurrent LSA in liver and cavitated liver mass
Baxter • 9YO MI GRD • LF 4th digit P3 nonhealing wound • digital OSA
Baxter • WLE P1 MC disarticulation • Carboplatin • 18mo later shifting leg lameness
Penelope • 15 YO FS mixed breed • MGT low grade AC and OVH removed 8 yrs ago • Newly excised malignant MGT
Hubert • 7 YO MC DSH • Periocular SCC
Valentino • 10 YO MC Miniature Schnauzer • Amelanotic melanoma rostral mandible
Shadow • 11 YO FS DSH • OSA of calvarium
Shadow • Tumor recurred 6 mos later • Euthanized
Lily • OSA R distal radius • Limbspare • Carboplatin
Lily • • • •
Doxorubicin 2 pulmonary mets 1.5yr later Metronomic chemotherapy HO & wagon
Lily • • • •
1 lung met spontaneous regression Lung metastectomy & liver lobectomy 2yr later Gemcitabine & carboplatin 3 yr later NED
Lily • 4 yr later hypercalcemia – LSA • Traumatic left CF lux – FHNO • 5 yr later died with relapsed LSA, renal OSA met, tumor thrombus cranial vena cava
Thank You, Questions?
Deanna Worley, Surgical Oncology
dworley@colostate.edu; (970) 297-4423 www.csuanimalcancercenter.org
Thoracic and Cardiovascular Surgery: Oncology Deanna Worley, DVM Diplomate, American College of Veterinary Surgeons, Small Animal ACVS Founding Fellow, Surgical Oncology Associate Professor, Surgical Oncology Flint Animal Cancer Center, Colorado State University
Goals • Review the different neoplasias occurring anatomically • Review diagnostic nuances • Review surgical technical aspects in treatment • Overall have an interactive experience
Chest wall resections • Common tumors – OSA, CSA, FSA/STS, Liposarcoma, MCT
• Staging – Bx, CT, bone scan
• Sx: ?# of ribs (6-7) – Ventilatory failure with more, less tolerated in cranial chest – Spinal/lubra plates with hemicerclage – Latissimus dorsi m. flap (muscle or myocutaneous) – Omentum, can provide airtight seal
Chest wall resections • Sx: – Marlex mesh • Gortex, Vicryl, bioSIST • 12.8x more complications with prosthetic • 3.0x more complications with composite
– Diaphragmatic advancement – Caudal lung lobectomy • Prevent VQ mismatch
– Stable Reconstruction, NO FLAIL! • Autogenous flaps, mesh, lubra plates
– Cat vs. dog
Chest wall • RT/SRS – Defined boundaries
• Chemo • MST • Monitoring
Sternum • Similar to chest wall • Marlex, Marlex-PMMA, heterogenous bonemesh, spinal plates, muscle flap (deep pectoral, latissimus dorsi) • Strict cage rest first day, u-cath
Chest wall/Sternum • Complications – Seroma – Pleural effusion – Peripheral/limb edema – Lameness – Infection – Dehiscence – Respiratory failure • Confirmational changes, aspiration pneumonia, sepsis, SIRS, ARDS
Brutus • 3 YO Doberman
Mesothelioma • Environment – Amphibole(=thin rodlike) asbestos (vs chrysotile=long curly serpentine, most common)
• Chromosomal aneuploidy • Diagnosis—difficult – Reactive mesothelial cells – Fibronectin – Suspected in adult dogs w/ chronic nonspecific fluid accumulation – Tissue biopsy
Mesothelioma • Treatment – Sx if solitary mass present – Palliative pericardiectomy • VATS vs thoracotomy
– Intracavitary cisplatin • 2-3mm depth of penetration
– Systemic doxorubicin or mitoxantrone
• Prognosis—about 1yr MST
Pleural • • • •
Mesothelioma Hematoma Lipoma Adenocarcinoma
Mediastinal and heart-based • Thymoma • Lymphoma • Chemodectoma/paragangliomoa/carotid body tumor/neuroendocrine • Ectopic thyroid • Brachial cysts • Mast cell tumor • Ectopic parathyroid • Open, sarcoma
Mediastinal and heart-based Tx options • • • •
Sx Radiation therapy Chemotherapy I 131
Thymoma • Symptoms – Respiratory distress – Precaval syndrome – Paraneoplastic • myasthenia gravis – Megaesophagus
• Hypercalcemia
– Exfoliative dermatitis in cats
Thymoma • Cytology – Lymphocytes: LSA or Thymoma? • Mast cells seen with thymomas
• Flow cytometry – Differentiate thymic lymphocytes (CD4+ & CD8+) vs thymic lymphoblasts=LSA (CD4+)
Thymoma • Tx options – Sx • Intercostal or median sternotomy • ≈70% resectable – Invasive, adherent – Debulk?
– RT – Chemo • Less successful than w/ LSA • Steroids for palliation
Thymoma • Prognosis – Myasthnia gravis • May not be reversible, may take months to know – Can develop postoperatively in cats
• Megaesophagus likely permanent
– If completely resected = good • >83% in dogs w/o megaesophagus 1 yr survival • 2yrs MST for cats
– If RT • MST about 9 mo for dogs, 2 yrs for cats ? • May enable eventual surgery
Pulmonary • Environment? • PE – HO • Lameness, swollen limbs, starts at the digits
– Digits • cats
• Staging – TXR – Abd U/S
Pulmonary • Diagnosis – FNA – Bronchoscopy, TTW, BAL – CT – WLE • Thoracotomy • VATS
– RT/IMRT/SRS—radiation pneumonitis – Chemotherapy
Pulmonary: Prognosis – Adenocarcinoma—based on location • MST 1 yr if: – Solitary, <5 cm, Node negative, No malignant effusion, Welldifferentiated
– Adenocarcinoma > SCC – Grade (low 16 mo, high grade 6 mo) – Clinical signs (none 18 mo, with MST 8 mo) – Stage (T1 26 mo, T2 7 mo, T3 3 mo; LN- 15mo, LN+ 1-2mo
Pulmonary: Prognosis – Pulmonary Lymphomatoid Granulomatosis • Complete response w/chemo in 1-2 weeks
– Malignant Histiocytosis • MST 4 to 6 mo, >90% met rate
– Feline • Primary less common • Grade (poorly dif 2.5 mo, mod diff 23 mo MST) • Metastasis to digits – “digit lung syndrome”
– HO • Lobectomy = immediate palliation • 3-4 months for radiographic resolution
Pneumonectomy Resection of all lung lobes, right or left side >75% lung removal = fatal Left lung 42% + right lung 58% = total volume Dogs tolerate <50% lung volume resection or left pneumonectomy if R lung healthy • Reinforce PRN bronchus with pleura/pericardium/fascia over stump • • • •
Metastectomy • 300 days post complete control of primary tumor • No other metastatic sites • Prior exposure to effective chemotherapy • Favorable histology • Radiographic doubling time greater than 30 days • Fewer than three lesions • ¼ to 1/3 can have longer than 1 yr MST
Trachea – Oncocytoma (rhabdomyoma) – OSA – Plasmacytoma – CSA – Carcinoma – Benign osteochondral masses
– – – – – – – –
FSA MCT ACA SCC LSA Leiomyomas Polyps Invasive thyroid ACA
Trachea • Diagnosis – Bronchoscopy – Open surgical – CT/MRI
• Tx options – Sx—Avoid tension!!!, end-to end anastomosis • SAFELY 3-4 rings – 20% older dogs (8-23), 25% younger dogs (3-10), 50%-60% experimentally in adult dogs – Massive tracheal resection not reported in the dog – 8 rings, 15-17 rings (~20-40% tracheal resection experimentally » Dogs 35-35 tracheal rings
Trachea • Tx options – Sx tricks • Tension-relieving techniques – Tension-relieving sutures, horizontal/vertical mattress – Tracheal stretch=incise annular ligaments – Laryngeal release=remove hyoid apparatus from thyroid cartilage – Mobilize patient head in flexion
• 1cm margins
– Palliative stenting – RT / PDT
Trachea • Px – rhabdomyomas > 1 yr MST – Plasmacytoma MST 1 yr – Palliative debulk with wire snare, MST 6 mo
• Complications – Stenosis • Excessive tension • Poor mucosal apposition
– Anastomatic breakdown/air leakage
Larynx • Vocal cordectomy laryngectomy – small benign vocal fold tumors, ventral approach
• Hemilaryngectomy – anecdotal – Myocutaneous flap?, temporary trach, ventral approach
• Epiglottectomy – Anecdotal, transoral approach
Larynx • Total laryngectomy – Controversial, NOT RECOMMENDED – Anecdotal – Ventral approach – Preplaced trach – Larynx removed en bloc with portion of hyoid apparatus – Permanent trach/tracheostoma – Gastrostromy tube, permanent?
Heart/Pericardium • HSA
• – Right atrium, auricle • • Chemodectomas • (=paragangliomas) • – Aortic body, carotid body • – Brachycephalic • breeds/hypoxia • • Mesothelioma • • • LSA •
Ectopic thyroid Undif sarcoma Myxoma/sarcoma Fibroma FSA Rhabdomyoma/sarcoma CSA Granular cell tumor OSA Metastatic
Heart/Pericardium diagnostic tests • Radiography • Echo • Pericardiocentesis – Cytology, pH
• Cardiac troponin I > cardiac troponin T • Pericardiography, pneumopericardiography, angiocardiography, gated radionuclide imaging • Endomyocardial biopsy • Thoracoscopy/Thoracotomy
Pericardial Pathology • (Size and location)
• Presence of effusion/Cardiac tamponade (↑ diastolic pressure, ↓ ventricular filling…↓SV &CO – Pulsus paradoxus (>10mmHg sys a during inspiration)
• Invasion of structures (caval syndrome) • Pericardial constriction Clinical Signs: Arrhythmia, pericardial effusion, CHF, syncope, pericardial fibrosis
Right auricular resection • Manual resection w/ tangential clamps – 1 cm margin
• TA stapler – 2 preplaced stay sutures – Reinforce staple line with continuous suture – Pericardial patch
• Venous inflow occlusion if tangential clamp can’t be placed – Preplaced sutures, loosen one Rumel before final sutures to de-air heart – How long?
Heart/Pericardial • HSA – MST 5-6 mo • Resection, subtotal pericardectomy, dox based chemo
• Chemodectoma • Resection usually not prudent but Bx! • Pericardiectomy – Regardless of pericardial effusion – Improves survival even if no effusion absent – ~20% metastasize
• Glue embolization for carotid body tumors
• Mesothelioma
Treating appendicular osteosarcoma in dogs Bernard SĂŠguin, DVM, MS dip ACVS, Founding Fellow, Surgical Oncology
Treatment Curative vs Palliative • Owners want to prolong survival • No detectable metastasis • Excellent/good overall health
• Owners do not want to prolong survival • Detectable metastases • Severe concurrent health problems
Curative intent treatment
Curative intent
treat primary tumor
amputation
limb sparing
treatment for metastatic disease
stereotactic radiation therapy
IV chemotherapy carboplatin doxorubicin cisplatin
Treating the local disease
Amputation • Complete forequarter • Coxofemoral disarticulation • En bloc amputationacetabulectomy for proximal femoral lesions
Limb sparing â&#x20AC;˘ Limb-sparing is well accepted for distal radial tumors â&#x20AC;˘ Prognosis for survival is equivalent for limbsparing and amputation
Straw, 1996
Survival of limb spare with infection • Dogs with an infection were less likely to die – HR= 0.446
• Lascelles, Ann Surg Oncol, 2005
Cortical allograft
Cortical allograft - complications • Infection – 39% - 70%
• Biomechanical problems – 11% - 60%
• Local recurrence – 15% - 60%
Limb-sparing techniques • Endoprosthesis – No difference in outcome between allograft and endoprothesis • Liptak, 2006
Limb-sparing • Techniques that can provide a viable vascular bone graft: – Bone transport osteogenesis – Vascular autograft
Bone transport osteogenesis
Degna et al, 2000
Bone transport osteogenesis Disadvantages â&#x20AC;˘ Repeated multiple daily distractions of ring apparatus (q 6 hours) â&#x20AC;˘ Time required to move bone segment across the radial defect (83 to 147 days)
Degna et al, 2000
Ulnar rollover transposition Vet Surg 32:69-79, 2003
Ulna rollover transposition
Lateral manus translation
Limb-sparing surgery • Other sites where limb-sparing can be amendable – Scapula – Ulna – Proximal femur with total hip replacement – Distal to antebrachiocarpal or hock joints • Partial foot amputation
Stereotactic radiosurgery
Entire tumor treated w/ single dose 30 Gy isodose (center receives ~40 Gy)
Dr. James Farese, University of Florida
1
Stereotactic RT Multiple arcs â&#x20AC;&#x201C; summation effect
+
Dr. James Farese, Florida State University
Curative-intent radiation therapy • • • • •
Radiation on gross tumor in 14 dogs Median total dose of 57 Gy (48-59.4 Gy) Fraction size 2.7 – 5.0 Gy/fraction All dogs improved in pain level and function 8 dogs had progression or recurrence of signs – Median local control 202 days (79-777) • Median survival: 209 days (79-781) Walter, VCO 2005
Treating the systemic disease
Adjuvant chemotherapy • • • •
Doxorubicin Cisplatin Carboplatin* Combination chemotherapy
Median survival time is 10-12 months
Adjuvant chemotherapy • Doxorubicin and cisplatin: cisplatin at 50 mg/m2 IV and doxorubicin at 15 mg/m2 IV next day q 3 weeks for total of 4 treatments in 16 dogs – Median survival: 18 months • Chun, J Vet Intern Med 2000
• Same protocol in 35 dogs – Median survival: 300 days • Chun, JAAHA 2005
Comparison of 5 protocols • • • • • • • •
Carboplatin q 3 weeks X4 Carboplatin q 3 weeks X6 Doxorubicin q 2 weeks X5 Doxorubicin q 3weeks X5 Alternating carbo and doxo q 3 weeks X 3 each Overall median DFI: 291 days Overall median ST: 284 days No difference in DFI or ST between protocols – Selmic 2014
Palliative intent treatment: controlling pain
Palliative therapy
amputation alone
Analgesics: opioids NSAIDS gabapentin/amantidine
radiation therapy
bisphosphonate
Radiation therapy • Different protocols – 8 to 10 Gy fraction on days 0, 7, and 21 – 74% responded: better likelihood to respond if given chemotherapy – Duration of response: 0 to 580 days – Median duration: 73 days
_Ramirez, 1999
Radiation Therapy • Four fractions, 8 Gy, 0,7,14,21 • Response noted in 92% of sites treated • Study of both appendicular and axial sites (n=26) in 24 dogs _Green, 2002
Radiation therapy • • • • • •
3 X 8 Gy or 4 X 6 Gy using electrons n = 54 dogs, 33 with chemotherapy 83% experienced pain relief Median duration of 53 days Both protocols were effective Chemotherapy did not improve response – Mueller et al, In Vivo 2005
Radiation therapy • • • • • •
Expedited palliative radiation protocol 8 Gy twice on 2 consecutive days 97% had positive response Median time to pain relief: 2 days Median duration of pain relief: 67 days Median survival time: 136 days • Knapp-Hoch JAAHA 2009
Drug therapy • Bisphosphonates – Anti-osteoclastic activity – Pamidronate*, etridonate, zoledronate, alendronate (Fosamax®)
Bisphosphonate - pamidronate • 43 dogs, pamidronate IV q 28 days at 1 mg/Kg (n=20) or 2 mg/Kg (n=23) – Median # of Tx: 3 (1-13) • 25% pain alleviation at 1 mg/Kg and 30% at 2 mg/Kg (overall 28%) • Median duration of pain alleviation: 246 and 224 days for each dose – No statistical difference • Unable to determine which dog will respond or not
Fan, JVIM 2007
Palliative Radiation and pamidronate • Adding pamidronate to the palliative radiation therapy protocol did not improve pain alleviation • Fan JVIM 2009
• Adding pamidronate to palliative radiation therapy provided a shorter survival time – Adding chemotherapy improved survival • xrt with chemo: median 307 days • xrt with pamidronate: median 69 days – Oblak Vet Surg 2012
Metronomic chemotherapy and toceranib • Study where dogs had amputation followed by 4 Tx of carboplatin and then – Cyclophosphamide and piroxicam • Alone • With toceranib
Metronomic protocol • piroxicam at 0.3 mg/kg PO EOD • cyclophosphamide at 10 mg/m2 PO EOD (alternating day of dosing with toceranib) • with or without toceranib at 2.75 mg/kg PO every other day (EOD)
Results • DFI: – 215 days without toceranib – 233 days with toceranib • p= 0.274
• Overall survival: – 242 days without toceranib – 318 days with toceranib • p= 0.08
Control is metronomic alone; London 2015
Control is metronomic alone; London 2015