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  1. 1. Chemotherapy-induced peripheral neurotoxicity (CIPN)<br />Guido Cavaletti - Wolfgang Grisold<br />University of Milano-Bicocca, Monza, Italy<br />Kaiser Franz Josef Hospital, Vienna, Austria<br />
  2. 2. 2<br />Learning aims<br />The aims of the video are:<br />to demonstrate how to recognize and properly assess the presence and severity of CIPN in cancer patients on a clinical basis<br />to teach when to prescribe additional examinations<br />Target audience<br /><ul><li>healthcare professionals dealing with cancer patients undergoing chemotherapy</li></ul>oncologists in training<br />The videos show <br />examples of medical interviews with patients with CIPN <br />a CIPN-focused neurological examination<br />
  3. 3. 3<br />Why is CIPN important?<br />It is dose limiting for cancer therapy<br />It can cause severe disability in patients<br />It can be long-term/persistent and symptoms may worsen even after treatment withdrawal<br />Currently no effective prophylactic/symptomatic therapy is available<br />
  4. 4. Neuropathy and pain<br />EFNS guidelines on neuropathic pain assessment: revised 2009, Eur J Neurol, 2010, 17, 1010-1018<br />NeuPSIG guidelines on neuropathic pain assessment, Pain, 2011 Jan;152(1):14-27<br />4<br />
  5. 5.
  6. 6. 6<br />Main characteristics of anticancer drugs causing neuropathy<br />Anticancer drugs causing neuropathy.<br /><ul><li>Platinum drugs
  7. 7. Cisplatin, oxaliplatin, carboplatin
  8. 8. Antitubulins
  9. 9. Paclitaxel, docetaxel
  10. 10. Epothilones
  11. 11. Vincristine, vinblastine
  12. 12. Thalidomide
  13. 13. Bortezomib</li></li></ul><li>7<br />Main characteristics of anticancer drugs causing neuropathy<br /><ul><li>Summary of the most typical symptoms/signs
  14. 14. Platinum drugs: sensory impairment with ataxia </li></ul> (+ acute cold-induced paresthesias with oxaliplatin)<br /><ul><li>Paclitaxel, docetaxel: distal sensory-motor neuropathy with myalgias
  15. 15. Epothilones: distal sensory-motor neuropathy
  16. 16. Vincristine: distal sensory-motor neuropathy with cranial nerves and autonomic impairment
  17. 17. Thalidomide: predominantly sensory neuropathy
  18. 18. Bortezomib: painful sensory neuropathy</li></li></ul><li>8<br />Main characteristics of anticancer drugs causing neuropathy<br /><ul><li>Typical cumulative dose threshold for the onset of CIPN using the most severely neurotoxic drugs
  19. 19. Cisplatin 350-400 mg/m2
  20. 20. Oxaliplatin 450-500 mg/m2
  21. 21. Paclitaxel 450-500 mg/m2
  22. 22. Docetaxel 300-350 mg/m2
  23. 23. Vincristine 3.6 mg/m2
  24. 24. Thalidomide 20 gr
  25. 25. Bortezomib: 15 mg/m2</li></li></ul><li>9<br />Neurological examination<br />9<br />9<br />
  26. 26. Nerve conduction studies (NCS) When order a NCS and what can be learnt?<br />Sural NCS<br />Common peroneal NCS<br />10<br />
  27. 27. 11<br />Nerve conduction studies (NCS) When order a NCS and what can be learnt?<br />Common peoneal nerve<br />Sural nerve<br />
  28. 28. 12<br />Nerve conduction studies (NCS) When order a NCS and what can be learnt?<br />Interpretation of results<br />Findings correlate with type of neuropathy <br />and severity, <br />not necessarily with the reported symptoms<br />
  29. 29. 13<br />Scales and scores: aims and pitfalls <br />NCI-CTC vs TNS: which tool is better for grading the severity of chemotherapy-induced peripheral neuropathy? Nat Clin Pract Neurol, 2008, 4, 68-69<br />Chemotherapy-Induced peripheral Neurotoxicity: a critical revision of the currently available tools, Eur J Cancer, 2010, 46, 479-494<br />
  30. 30. 14<br />Conclusions<br />CIPN is a clinically-relevant problem in cancer patients <br />It can be dose-limiting, frequently it is treatment-resistant and it impairs the quality of life of affected patients<br />Frequently it is not properly assessed<br />Nerve conduction studies can be helpful to better characterize CIPN, but it should not be used in all patients<br />Discrepancy can exist between patient-reported symptoms and nerve conduction studies <br />
  31. 31. 15<br />Next<br />Summary<br />CIPN is a clinically-relevant side effect of the modern treatment of solid and hematologic malignancies. However, frequently CIPN is not properly assessed in clinical practice and treatment is difficult.<br />This presentation shows examples of simple methods to perform an objective neurological examination aimed at the detection and assessment of CIPN.<br />The role of nerve conduction studies in CIPN patients is also critically reviewed.<br />Finally, the presence of possible pitfalls in the routine use of several of the currently available scales used to score the severity of CIPN is highlighted.<br />
  32. 32. 16<br />Biographies of the authors<br />Next<br />Prof. Guido Cavaletti is a neurologist at the Department of Neurology of the S. Gerardo Hospital in Monza and is the head of the Experimental Neurology Unit at the Department of Neuroscience and Biomedical Technologies (DNTB) of the University of Milano “Bicocca”, Monza, Italy.<br />He performed his earliest clinical studies on CIPN in 1990 and subsequently he developed most of the CIPN preclinical models currently available to study the mechanisms of this severe complication of cancer treatment.<br />He is the principal investigator of the CI-PERINOMS international study devoted to the identification of validated methods to assess CIPN.<br />Prof. Wolfgang Grisold is a neurologist at the Kaiser Franz Josef Hospital and Ludwig Boltzmann Institute (LBI) for neuro-oncology in Vienna. He is both trained in electrophysiology and in neuropathologic evaluation of peripheral nerves. He has a long standing interest in neuro-oncology, in particular the side effects of tumour treatment in the peripheral nervous system. <br />The neuro-oncologic group in Vienna is also interested in primary brain tumours, leptomeningeal metastasis and paraneoplastic syndroms. <br />
  33. 33. 17<br />Institutions<br />Next<br />The University of Milano “Bicocca” was founded in 1998 and despite it is one of the youngest in Italy it was ranked in 2009 at the 6th position among the 82 Italian Universities by the Italian University and Research Ministry. <br />The DNTB is settled at the U8 Building of the University of Milano “Bicocca”. It is one of the four Departments composing the Medical Faculty and it is located at the Medical campus in Monza, close to the 800 beds S. Gerardo University Hospital where the assessment of chemotherapy-treated patients is performed by a collaborative neurology-oncology team.<br />The Kaiser Franz Josef Hospital (SMZ Süd) of the city of Vienna, is one of the largest hospitals in Vienna and is a teaching hospital of the University of Vienna. In total it has about 1000 beds. One of its designated activities is Oncology<br />Neuro-oncology is performed within a tumour board, assembled from neurology, neurosurgery, general oncology, radiotherapy, with a close cooperation with pathology and radiology. National and international clinical neuro-oncological studies, mainly on brain tumor patients, chemotherapy-induced neuropathies and paraneoplastic syndromes, are performed within the LBI-Neurooncology at the KFJ HospItal in Vienna<br />
  34. 34. 18<br />Next<br />Acknowledgements<br />The assistance provided by the European Association for Neuro-Oncology (EANO) in the revision of this video is gratefully acknowledged.<br />The authors are also grateful to the patients who agreed to collaborate in the preparation of the medical interview and to the friends who gifted their voices.<br />This presentation has been realized by the Multimedia Production Center of the University of Milano-Bicocca with the collaboration of the S. Gerardo Hospital in Monza.<br />
  35. 35. 19<br />References<br />Next<br />Chemotherapy-induced peripheral neurotoxicity. Cavaletti G, Marmiroli P. Nat Rev Neurol. 2010 Dec;6(12):657-66.<br />Toxic peripheral neuropathy associated with commonly used chemotherapeutic agents. Argyriou AA, Zolota V, Kyriakopoulou O, Kalofonos HP. J BUON. 2010 Jul-Sep;15(3):435-46<br />Cleeland CS, Farrar JT, Hausheer FH. Assessment of cancer-related neuropathy and neuropathic pain. Oncologist. 2010;15 Suppl 2:13-8. <br />Chamberlain MC. Neurotoxicity of cancer treatment. Curr Oncol Rep. 2010 Jan;12(1):60-7. <br />Giglio P, Gilbert MR. Neurologic complications of cancer and its treatment. Curr Oncol Rep. 2010 Jan;12(1):50-9. <br />Paice JA. Clinical challenges: chemotherapy-induced peripheral neuropathy. Semin Oncol Nurs. 2009 May;25(2 Suppl 1):S8-19.<br />Kaley TJ, Deangelis LM. Therapy of chemotherapy-induced peripheral neuropathy. Br J Haematol. 2009 Apr;145(1):3-14.<br />Windebank AJ, Grisold W. Chemotherapy-induced neuropathy. J Peripher Nerv Syst. 2008 Mar;13(1):27-46. <br />