Minimally Invasive Diagnosis. Solid Tumor Percutaneous Core Biopsy. Sheath & spring loaded needle. Specimen submission for solid tumors

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1 38 th Congress of the International Society of Paediatric Oncology September 2006 Minimally Invasive Diagnosis and Treatment of Pediatric Malignancies through Interventional Radiology Minimally Invasive Diagnosis Percutaneous biopsy of solid tumor malignancies Needle localization Fluid aspiration or biopsy of hematologic malignancies Fredric A. Hoffer,, MD Pediatric Interventional Radiologist St. Jude Children s Research Hospital Solid Tumor Percutaneous Core Biopsy Sheath & spring loaded needle Guidance: US, CT and/or fluoroscopy Coaxial needle often used Spring loaded core biopsy needles: median gauge 15 (range 13-20) Multiple samples: median 5 (range 1-17) Avitene slurry except in lung Specimen submission for solid tumors 10% formalin: 2+ cores for Histopathology including Immunohistochemical staining RPMI 1640:2 cores each for PCR for typical solid tumor translocations FISH for NMYC for neuroblastoma DNA index for neuroblastoma Cytogenetics for rare tumors Percutaneous biopsy of solid tumor malignancies Patients 1-33 yrs (mean 10yr; adults included if acquired disease as pediatric patient) 202 solid tumor biopsies: 105 for initial Dx; 97 for recurrence 121 TP, 67 TN, 14 FN, 0 FP Sensitivity 90% Specificity 100% Accuracy 93% 1

2 Initial percutaneous biopsy in pediatric patients to determine malignancy 105 initial biopsies 65 TP, 38 TN, 2FN (thyroid) Sensitivity 97% Specificity 100% Accuracy 98% Garrett KM, Fuller CE, Santana VM, Shochat SJ, Hoffer FA. Percutaneous biopsy of pediatric solid tumors. Cancer 104: ; Advances in pathology allowed diagnosis of pediatric tumors from imaging guided techniques Histopathology rather than cytology Cytogenetics Fluorescent in situ hybridization Flow cytometry Molecular pathology Immunohistochemistry Needle localization of small tumors Kopans 20G needle & hooked wire Hooked needle placed under US or CT Methylene blue 0.1 ml also used for small lung nodules then excised thoracoscopically All 9 lesions < 1 ml in volume successfully excised Alternative diagnosis: biopsy of lung lesions as small as 2mm under US Alternative treatment: thermal ablation Needle localization of rhabdomyosarcoma metastasis Diagnosis of Hematologic Malignancies Materials:4-year period, 22 patients Methods: 1 needle localization: FN 6 fluid aspirations & 3 catheter drainages: 8 TP & 1 FN 25 percutaneous biopsies: 16 TP, 3 TN, & 6 FN Overall results Sensitivity 75% Specificity 100% Accuracy 77% 2

3 Non-Hodgkin Lymphoma Aspiration/drainage 5 TP, 1 FN Percutaneous biopsy 9 TP, 1 TN, 2 FN Overall results: Sensitivity 82% Specificity 100% Accuracy 83% Hodgkin Lymphoma Needle localization 1 FN Percutaneous biopsy 6 TP, 2 TN, 1 FN Overall results: Sensitivity 75% Specificity 100% Accuracy 80% If a child has a suspected leukemia or lymphoma and the bone marrow biopsy is not diagnostic, radiological interventions are minimally invasive and accurate alternatives for diagnosis Garrett KM, Hoffer FA, Behm FG, Gow KW, Hudson MM, Sandlund JT. Interventional radiology techniques for the diagnosis of lymphoma or leukemia. Pediatr Radiol 32: , FDG PET offers alternative to percutaneous biopsy after treatment HD at Diagnosis After 8 weeks: FDG CR Minimally invasive treatment Thrombolysis and venous angioplasty Pleurodesis Thermal ablation of pediatric malignancies Thoracic inlet syndrome bilaterally 3

4 Thoracic inlet + subclavian line = stenosis and thrombosis Clot post angioplasty Helix Clot Buster thrombectomy device ( Thrombectomy device macerates clot to 25 micron size particles After angioplasty & thrombectomy Subclavian vein vs. internal jugular venous access % Thombosed 60% 50% 40% 30% 20% 10% 0% Thrombosis vs. access Blood 101:4273-8, 2003 SCV IJ Percutaneous Access 4

5 Pleurodesis: 7 pediatric cancer patients (age 3 to 21 years) intractable pleural effusions at the end of life 11 pleurodeses 5 patients had unilateral pleurodeses 2 had a unilateral followed by bilateral pleurodeses. Methods: Chest tube placed percutaneously 10Fr preferred Ten of the 11 pleurodeses were performed under anesthesia. Doxycycline 500mg in 40 ml of NS for 30 minutes in each pleural cavity Patient tossed then material aspirated Results: Median Drainage 1000ml 24 hrs post chest tube 1 day pre pleurodesis (0-26) 200ml 24 hrs pre pleurodesis 60ml 24 hrs post pleurodesis 6 days after pleurodesis (1-28) 33ml 24 hrs pre tube removal Chest tube lowered RR (p=0.0156) Improvement remained after pleurodesis and chest tube removal (p=0.0313) breathes per minute Prior to Chest Tube Insertion Respiratory Rate After Insertion After Pleurodesis & Chest Tube Removal At Last Clinical Encounter Seven year old girl with multifocal osteosarcoma FDG/PET 10Fr catheter used for pleurodesis 5

6 CT Day 9 post pleurodesis Died day 49 post pleurodesis Autopsy: Right chest cavity (post pleurodesis) Near total obliteration by tumor Tumor encases entire lung Tumor adherent to chest wall Tumor pushing against trachea Left chest cavity Lung significantly less adherent to pleura Lung studded with metastatic tumor nodules 600 ml pleural effusion Pleurodesis Results: Pain and Relief Pain from the pleurodesis 4 to 10 (median 5) duration < 1 day Two patients were without a chest tube for 5 to 6 days before their death in the hospital Five patients returned home to live 10 to 49 days (median 19 days) after discharge Only one patient kept one chest tube in until death at home Conclusion: Successful pleurodesis does not depend on the amount of previous pleural fluid production. Pediatric oncology patients with pleural effusions: Benefit symptomatically from pleurodeses Can return home for terminal care without a chest tube Radio Frequency Ablation (RFA) of Pediatric Malignancies Experience in three parts Mainly pre protocol hepatic Phase 1 musculoskeletal Phase 1 pulmonary Design St. Jude had the only open protocol for RFA in pediatric malignancy Phase 1 design Inclusion criteria: prior resection of pulmonary metastasis Accrued 12 patients with lung metastases 8 osteosarcoma 1 each: synovial sarcoma, hepatoma, adrenocortical carcinoma, Wilms tumor Imaging at baseline, 1 & 3 months post RFA 6

7 Recurrent pulmonary osteosarcoma ideal for RFA Initial thoracotomy finds more osteosarcoma metastases than seen on CT 90% proven recurrent metastases after initial thoracotomy 50% recurrences were in the pulmonary scar after resection McCarville M. Beth, Kaste SC, Goloubeva O, Rao BN, Pratt CB. Cancer 2001; 91: Pulmonary RFA RFA is alternating current delivered at the the radiofrequency from a needle placed directly in a tumor Neighboring vessels >4mm & airways >1mm are not damaged Neighboring nerves & spinal cord can be damaged by temperatures > 45 0 C Tumor ablated at temperatures > C RF coagulator RFA Methods Radionics / Valley Lab cold perfusion of the probes enlarges burn volume by avoiding gas formation and charring Cluster (triple) 2 cm single CT guidance: in room monitoring and spot CT sectioning RFA procedures 1-3 metastases burned per setting (median 2) Limit 4 hours anesthesia time per setting 38 lesions attempted RF ablation Lesion LD: 1.5 to 18 cm (median 3.5 cm) Burn volumes: 21 to 555 ml (median 86 ml) 14 year old with osteosarcoma 2 prior thoracoscopic resections refused further surgery RFA for cure: CT & FDG-PET 7

8 2cm RFA probe pre burn Close to neural foramen 20G SMK needle & temperature probe Temperature monitor: 45 0 C max in neuroforamen 56 0 C max in tumor RFA post burn L pleural lesion pre & post RFA 8

9 One month post RFA FDG-PET/CT no enhancement, rim enhancement and hilar adenopathy 6 months post RFA Recurrence FDG-PET/CT pre 2 nd RFA session Repeat RFA Triple probe used. Angled away from spinal canal Max temperature 81 0 C 7 burns 72 roll-overs Total burn time 54 minutes PET/CT 1 month after repeat RFA Rim enhancement 3 months post 2 nd RFA Rim enhancement collapsed. Complete ablation. Alive and well after 2 years 9

10 12 yo with Osteosarcoma Post multiple resections RFA for palliation Pre RFA FDG-PET One month post RFA 3 complete ablations, 2 recurred later DOD at 12 months Toxicity Hyperthermia during procedure Pain Tumor lysis Skin burns Pulmonary complications Hyperthermia during RF ablation Highest core temperature C Who is at risk? Small patients Large tumors Tumors close to large vessels Predicting hyperthermia [Energy (Watts) x time (sec)] / [Mass (Kg) x 3470] = temp increase predicted (ºC) Hoffer FA, Madeira-Campos, A Heat loss encouraged Hyperthermia Treatment Minimal covers Start with mild hypothermia Polar Bair-Hugger cool air conditioned blanket Stop the RFA at 40 0 C core temperature Tumor lysis in 8/12 patients RF ablated No blood chemistry elevation (K, phos, or uric acid) Duration of symptoms: 2-40 days (median 14 days) Fever: Rx: acetaminophen, ibuprofen Myoglobinuria: 5 patients All patients treated with IV hydration No renal damage Fatigue Nausea 10

11 Skin burns 3 burns at grounding pad all healed spontaneously 1 burn at knuckle and thigh (reentry phenomenon) healed spontaneously All but one skin burn over pulmonary site avoided by application of an iced glove Pulmonary Complications No PTX or pleural effusion required chest tube (one placed prophylactically) 2 Bronchopleural fistulae (both drained with a catheter & infused with tpa) 2 Dyspnea with normal activity until death Other pulmonary complications illustrated: 500 ml right paratracheal osteosarcoma partially RF ablated: SVC syndrome Ossified AP window metastasis from osteosarcoma Required bone biopsy needle for RF probe placement RFA complicated by bradycardia Wilms tumor lung metastases RFA of L peri-mediastinal lesions Lesions targeted were FDG active Three months later imaging suggested eventration of L diaphragm 11

12 MR suggested phrenic nerve paralysis: expiration, inspiration Recent broncho-pulmonary vein fistula Pulmonary RFA Results Incomplete ablation 13/38 (34%) Complete ablation 25/38 (66%) Recurrence 7/32 (22%) Durable ablation 12/32 (38%) Survival after RFA 2 alive and well: 18, 20 months 2 alive with disease: 14,18 months 8 died of disease: 5-25 (median 11) months Median Survival: 12 months Toxicity vs. Survival: Median Pain Tumor lysis Dyspnea at rest Survival 5 days 12 days 1 of 12 patients 12 months Future Direction Most promising for osteosarcoma after first thoracotomy RFA or other thermal ablation methods (cryotherapy, microwave, laser, focused US) can kill a tumor completely where radiotherapy (ischemia) chemotherapy (poor diffusion) have failed 12

13 THE TERMINATORS HOFFER End Fredric A. Hoffer,, MD Photo of Arnold Schwarzenegger More medical education materials are available at: You may print and download content for personal educational use only. All material is copyrighted by the author of the content or St. Jude Children s Research Hospital. See legal terms and conditions at 13