Il sistema scheletrico rappresenta nei tumori solidi la terza sede metastatica in ordine di frequenza, dopo fegato e polmoni. Di tutti i segmenti ossei, il rachide risulta essere quello maggiormente interessato. Dal punto di vista prognostico, il coinvolgimento osseo consente sopravvivenze relativamente più lunghe, ma è in grado di condizionare la qualità di vita pesantemente. L'integrazione terapeutica multispecialistica è indispensabile per una corretta valutazione diagnostica e terapeutica. Il trattamento comprende il controllo della malattia neoplastica di base e la terapia delle manifestazioni conseguenti alle metastasi ossee: compressione midollare, dolore, ipercalcemia, complicanze internistiche. Il trattamento oncologico specifico dipende fondamentalmente dallo stadio di malattia, dall'eventuale concomitante coinvolgimento viscerale, dalla ormonodipendenza e dalla chemiosensibilità della patologia neoplastica di base.
BartholdiDRubinBP: VEGF mRNA induction correlates with changes in the vascular architecture upon spinal cord damage in the rat. Eur J Neurosci9: 2549–2586, 1997.
3.
BenfordHLMcGowanNW: Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro. Bone28(5): 465–473, 2001.
BoogerdWvan der SandeJJ: Effective systemic therapy for spinal epidural metastases from breast carcinoma. Eur J Cancer Clin Oncol25: 149–153, 1989.
6.
BoogerdWvan der SandeJJ: Treatment of complications: diagnosis and treatment of spinal cord compression in malignant disease. Cancer Treat Rep19: 129, 1993.
7.
BurchPAGrossmanSA: Treatment of epidural cord compression from Hodgkin's disease with chemotherapy. Am J Med84: 555–558, 1988.
8.
BuzdarAU: Endocrine therapy in the treatment of metastatic breast cancer. Semin Oncol28(3): 291–304, 2001.
9.
ColemanRE: Skeletal complications of malignancy. Cancer80 (suppl 8): 1588–1594, 1997.
10.
ColemanRE: Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev27 (3): 165–176, 2001.
11.
ColemanRE: How can we improve the treatment of bone metastases further?Curr Opin Oncol10 (suppl 1): S7–13, 1998.
CooperKBajorinD: Decompression of epidural metastases from germ cell tumors with chemotherapy. J Neurooncol8: 275–280, 1990.
14.
CriscuoloGRBalleduxJP: Clinical neurosciences in the decade of the brain: hypotheses in neuro-oncology. VEG/PF acts upon the actin cytoskeleton and is inhibited by dexamethasone: relevance to tumor angiogenesis and vasogenic edema. Yale J Biol Med69: 337–355, 1996.
15.
DafermouAColamussiP: A multicentre observational study of radionuclide therapy in patients with painful bone metastases of prostate cancer. Eur J Nucl Med28 (7): 788–798, 2001.
16.
EsbritP: Hypercalcemia of malignancy—new insights into an old syndrome. Clin Lab47 (1–2): 67–71, 2001.
17.
FriedmanHMSheetzS: Combination chemotherapy and radiation therapy. The medical management of epidural spinal cord compression from testicular cancer. Arch Intern Med146: 509–512, 1986.
18.
FuruyaYAkakuraK: Endocrine therapy for recurrence after definitive radiotherapy in patients with prostate cancer. Int J Urol8 (5): 222–226, 2001.
19.
FusterDHerranzD: Usefulness of strontium-89 for bone pain palliation in metastatic breast cancer patients. Nucl Med Commun21 (7): 623–626, 2000.
20.
GandaraDRLaraPNJr: Integration of new chemotherapeutic agents into chemoradiotherapy for stage III non-small cell lung cancer: focus on docetaxel. Semin Oncol28–3 (suppl 9): 26–32, 2001.
21.
GonzalezMVGonzalez-SanchoJM: Hormone-activated nuclear receptors inhibit the stimulation of the JNK and ERK signalling pathways in endothelial cells. FEBS Lett459: 272–276, 1999.
22.
GoverAKumarPD: Hypercalcemia induced by parathyroid hormone-related peptide after treatment of carcinoma. South Med J95 (2): 258–260, 2002.
23.
GrantRPapadopoulosSM: Metastatic epidural spinal cord compression: current concepts and treatment. J Neurooncol19: 79–92, 1994.
24.
GreenbergHSKimJH: Epidural spinal cord compression from metastatic tumor: results with a new treatment protocol. Ann Neurol8: 361–366, 1980.
25.
HayashiTSakuraiM: Expression of angiogenic factors in rabbit spinal cord after transient ischaemia. Neuropathol Appl Neurobiol25: 63–71, 1999.
26.
HayesFAThompsonEI: Chemotherapy as an alternative to laminectomy and radiation in the management of epidural tumor. J Pediatr104: 221–224, 1984.
27.
HeissJDPapavassiliouE: Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats. Involvement of the glucocorticoid receptor and vascular permeability factor. J Clin Invest98: 1400–1408, 1996.
28.
Helweg-LarsenS: Clinical outcome in metastatic spinal cord compression. A prospective study of 153 patients. Acta Neurol Scand94: 269–275, 1996.
29.
HooverMBowmanLC: Long-term outcome of patients with intraspinal neuroblastoma. Med Pediatr Oncol32: 353–359, 1999.
30.
HortobagyiGNTheriaultRL: Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. J Clin Oncol16 (6): 2038, 1998.
31.
HusbandDJ: Malignant spinal cord compression: prospective study of delays in referral and treatment. BMJ317 (7150): 18–21, 1998.
32.
IkedaHUshioY: Edema and circulatory disturbance in the spinal cord compressed by epidural neoplasms in rabbits. J Neurosurg52: 203–209, 1980.
33.
JagdevSPColemanRE: The bisphosphate, zoledronic acid, induces apoptosis of breast cancer cells: evidence for synergy with paclitaxel. Br J Cancer84 (8): 1126–1134, 2001.
34.
KatagiriHTakahashiM: Clinical results of nonsurgical treatment for spinal metastases. Int J Radiat Oncol Biol Phys42: 1127–1132, 1998.
35.
KatoAUshioY: Circulatory disturbance of the spinal cord with epidural neoplasm in rats. J Neurosurg63: 260–265, 1985.
36.
KimRYSpencerSA: Extradural spinal cord compression: analysis of factors determining functional prognosis - a prospective study. Radiology176: 279, 1990.
37.
KingDGoodmanJ: Dumbbell neuroblastomas in children. Arch Surg110: 888–891, 1975.
38.
KlekampJGJarzeckaK: Vascular endothelial growth factor is expressed in ovine pulmonary vascular smooth muscle cells in vitro and regulated by hypoxia and dexamethasone. Pediatr Res42: 744–749, 1997.
39.
KristensenBEjlertsenB: Prednisolone in the treatment of severe malignant hypercalcemia in metastatic breast cancer: a randomized study. J Intern Med232: 237–245, 1992.
40.
KunklerI: Radiotherapy for breast cancer. N Engl J Med346 (11): 862–864, 2002.
41.
LandisSHMurrayT: Cancer statistics, 1999. CA Cancer J Clin49 (1): 8, 1999.
42.
LandmannCHunigR: The role of laminectomy in the combined treatment of metastatic spinal cord compression. Int J Radiat Oncol Biol Phys24: 627–631, 1992.
43.
LeeMVFongEM: Bisphosphonate treatment inhibits the growth of prostate cancer cells. Cancer Res61(6): 2602–2608, 2001.
44.
LoblawDALaperriereNJ: Emergency treatment of malignant extradural spinal cord compression: an evidence-based guideline. J Clin Oncol16: 1613–1624, 1998.
45.
LortholaryA: Tumor-induced hypercalcemia. Review of bisphosphonate treatment. Rev Med Interne22 (7): 648–652, 2001.
46.
LoRussoP: Analysis of skeletal-related events in breast cancer and response to therapy. Semin Oncol28–4 (suppl 11): 22–27, 2001.
47.
Lucchi-AngellierE: Hormone therapy and breast cancer: a review. Rev Med Interne22 (12): 1213–1224, 2001.
48.
MacbethF: Radiation myelitis and thoracic radiotherapy: evidence and anecdote. Clin Oncol (R Coll Radiol)12 (5): 333–334, 2000.
49.
MaranzanoELatiniP: Radiotherapy without steroids in selected metastatic spinal cord compression patients. A phase II trial. Am J Clin Oncol19: 179–183, 1997.
50.
MaranzanoELatiniP: Short-course radiotherapy (8 Gy × 2) in metastatic spinal cord compression: an effective and feasible treatment. Int J Radiat Oncol Biol Phys38: 1037–1044, 1997.
51.
MarshallLFLangfittTW: Combined therapy for metastatic extradural tumors of the spine. Cancer40: 2067–2070, 1977.
52.
MartensonJAEvansRG: Treatment outcome and complications in patients treated for malignant epidural spinal cord compression (SCC). J Neuro-Oncol3: 77, 1985.
53.
MehtaVKPoenJ: Radiotherapy, concomitant protracted-venous-infusion 5-fluorouracil, and surgery for ultrasound-staged T3 or T4 rectal cancer. Dis Colon Rectum44 (1): 52–58, 2001.
54.
PayneRBCarverME: Interpretation of serum total calcium: effects of adjustment for albumin concentration on frequency of abnormal values and on detection of change in the individual. J Clin Pathol32: 56–60, 1979.
55.
PortenoyRK: The nature of opioid responsiveness and its implications for neuropathic pain: new hypotheses derived from studies of opioid infusions. Pain43: 273–286, 1990.
56.
RadesDBlachM: Metastatic spinal cord compression. Influence of time between onset of motoric deficits and start of irradiation on therapeutic effect. Strahlenther Onkol175: 378–381, 1999.
57.
ReinholzGGGetzB: Bisphosphonates directly regulate cell proliferation, differentiation, and gene expression in human osteoblasts. Cancer Res60 (21): 6001–6007, 2000.
58.
RipamontiCFulfaroF: Pathogenesis and pharmacological treatment of bone pain in skeletal metastases. Q J Nucl Med45 (1): 65–77, 2001.
59.
RubinP: Extradural spinal cord compression by tumor. Part I: experimental production and treatment trials. Radiology263: 1243, 1993.
60.
SandersonIRPritchardJ: Chemotherapy as the initial treatment of spinal cord compression due to disseminated neuoblastoma. J Neurosurg70: 688–690, 1989.
61.
SasagawaJGutonH: Hormonal treatment of symptomatic spinal cord compression in advanced prostate cancer. Int Urol Nephrol21: 351–356, 1991.
62.
SchiffDO'NeillBP: Intramedullary spinal cord metastases: clinical features and treatment outcome. Neurology47: 906, 1996.
63.
SiegalTShohamiE: Indomethacin and dexamethasone treatment in experimental spinal cord compression. Part I. Effect on water content and specific gravity. Neurosurgery22: 328, 1988.
64.
SiegalTShoshamiE: Indomethacin and dexamethasone treatment in experimental spinal cord compression. Part II. Effect on edema and prostaglandin synthesis. Neurosurgery22: 334, 1988.
SorensonSHelweg-LarsenS: Effect of high-dose dexamethasone in carcinomatous metastatic spinal cord compression treated with radiotherapy: a randomised trial. Eur J Cancer30A: 22–27, 1994.
69.
SteinbrechDSMehraraBJ: VEGF expression in an osteoblast-like cell line is regulated by a hypoxia response mechanism. Am J Physiol Cell Physiol278: C853–860, 2000.
70.
SundaresanNSachdevVP: Surgical treatment of spinal cord compression from epidural metastasis. J Clin Oncol13: 2330–2335, 1995.
71.
TarlovIM: Spinal cord compression studies. III. Time limits for recovery after gradual compression in dogs. Arch Neurol Psychiatry71: 588, 1954.
72.
TassonePForcinitiS: Growth inhibition and synergistic induction of apoptosis by zoledronate and dexamethasone in human myeloma cell lines. Leukemia14 (5): 841–844, 2000.
73.
TheriaultRLLiptonA: Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized placebo-controlled trial. J Clin Oncol17 (3): 846–854, 1999.
74.
TokuhaschiKMatsuzakiH: Scoring system for the preoperative evaluation of metastatic spine tumor prognosis. Spine15: 1110–1113, 1990.
75.
TomitaTToribatakeY: Total en bloc spondylectomy and circumspinal decompression for solitry spinal metastasis. Paraplegia32: 36–46, 1994.
76.
TurnerSMarosszekyB: Malignant spinal cord compression: a prospective evaluation. Int J Radiat Oncol Biol Phys26: 141–146, 1993.
VokesEEKiesMS: Concomitant chemoradiotherapy as primary therapy for locoregionally advanced head and neck cancer. J Clin Oncol18 (8): 1652–1661, 2000.
80.
YangCHTsaiCM: Gemcitabine and cisplatin in a multimodality treatment for locally advanced non-small cell lung cancer. Br J Cancer86 (2): 190–195, 2002.
81.
WindsorPM: Predictors of response to strontium-89 (Metastron) in skeletal metastases from prostate cancer: report of a single centre's 10-year experience. Clin Oncol (R Coll Radiol)13 (3): 219–227, 2001.
