Tumori

Extra central nervous system metastases from cerebral glioblastoma multiforme in elderly patients. Clinico-pathological remarks on our series of seven cases and critical review of the literature

Manolo Piccirilli, Giacoma Maria Floriana Brunetto, Giovanni Rocchi, Felice Giangaspero, Maurizio Salvati

¹Department of Neurological Sciences-Neurosurgery, and ²Department of Experimental Medicine and Pathology, University of Rome “Sapienza”, Rome; ³Neurosurgery, INM-Neuromed, Pozzilli (IS), Italy

Key words: elderly patients, glioblastoma multiforme, metastases

abstract

Aims and background. The aim of the study was to evaluate the treatment of the extracranial metastases from glioblastoma multiforme in the elderly, discussing their uncommon occurrence and their pathogenesis.

Methods. The authors report seven cases of elderly patients (mean age, 69 years), with an initial diagnosis of cerebral glioblastoma multiforme, treated by a grossly total surgical removal and followed by adjuvant radiotherapy (64 Gy in 6 weeks, using Linac) and adjuvant chemotherapy (temozolomide both concomitant and sequential to radiotherapy).

Results. All patients presented a postoperative course characterized by good functional and clinical conditions (Karnofsky performance scale ≥70), which remained unchanged for a mean period of about 21 months (range, 16-23), with no neuroradiological signs of lesion regrowth. After this interval, new clinical signs occurred, and their clinical and radiological investigation showed metastatic repetitions in different sites: lung, liver, humerus and lymph nodes. All the metastases were surgically treated, but regrowth of the brain tumor and progression to deep important neural structures caused the patients’ exitus after a mean interval of about 10 months (range, 8-12) from the diagnosis of metastasis.

Conclusions. We found 128 cases of extra CNS metastases in the English literature. The main features of the patients of the previous reports and of those of the present series were analyzed. The main modalities of glioblastoma multiforme spread, the few theories about the rarity of metastasis, and the probable biological, histological and immunogenetic mechanisms involved in the pathogenesis are described. Although several studies have reported a poor outcome in elderly patients, they affirm that the treatment of those with a Karnofsky performance status >60 should be just as aggressive as in younger patients. This allows them to obtain a longer survival time and to also treat metastases, which are uncommon particularly in the elderly.

Introduction

Glioblastoma multiforme (GBM) is a highly malignant glioma with a low potential to metastasize outside the confines of the central nervous system. Although the rarity of this condition is well documented in the literature, patients now have a longer survival than in the past due to improvement in treatment modalities (Figures 1-2). Thus, we can note a significant increase in the incidence of GBM cases with extracranial repetitions. The first documented metastatic glial tumor was described by Davis in 1928¹ under the diagnosis of spongioblastoma multiforme. If we consider that the reported frequency of extraneural metastases was 0.44% in 1966², we can point out a sensitive increase until the present value of about 2%³.

We present 7 cases of GBM in elderly patients with distant metastases to the lung, liver, arm and lymph nodes. The potential pathogenetic mechanisms, the main routes of spread to extracranial sites, and the problems related to treatment in elderly patients are discussed.

Materials and methods

Case 1. A 66-year-old man presented a right frontal lobe lesion, which histologically proved to be a GBM. Gross total removal of the tumor was performed. The patient underwent adjuvant radiotherapy (64 Gy in 6 weeks using Linac) and adjuvant chemotherapy with the administration of temozolomide, first concomitantly to radiotherapy (75 mg/m²/die), then sequentially (200 mg/m²/die for 5 days in each cycle of 28 days, for 6 cycles).

MRI-imaging follow-up at 16 months did not reveal any signs of local recurrence, the Karnofsky performance status (KPS) was 80, but the patient started to present hemoptysis and cough. He was thus studied with a thoracic CT scan that revealed a left apical lung lesion. The patient underwent a lung lobectomy. The histological examination showed the same features of the primary tumor, and a diagnosis of GBM metastatic lesion was made. A whole-body CT scan did not evidence additional lesions. Six months later the primary brain tumor presented a regrowth located in the corpus callosum and central ganglia; his conditions deteriorated and he died after 3 months (Table 1).

Table 1 - Our case series

Case No., age, sex	GBM localization	Metastatic localization, and time of occurrence (mo)	CNS GBM progression from diagnosis of metastasis (mo)	Death of the patient after CNS progression (mo)	Overall survival (mo)

Case 1, 66, M	R frontal lobe	Lung, 16	6	3	25
Case 2, 74, F	R temporal lobe	Liver, 18	6	2	26
Case 3, 67, F	L frontal lobe	Humerus, 19	8	3	30
Case 4, 72, M	R occipital lobe	Lung, 21	7	3	31
Case 5, 63, M	R temporal lobe	Lung, 19	8	2	29
Case 6, 70, F	R frontal lobe	Lymph nodes, 20	8	2	30
Case 7, 69, M	R temporal lobe	Lung, 23	9	3	35

R, right; L, left.

Case 2. A 74-year-old woman was treated for a right temporal lobe GBM. A craniotomy was performed, followed by a grossly total resection. She was given adjuvant radiotherapy (64 Gy in 6 weeks using Linac) and adjuvant chemotherapy with temozolomide, first concomitantly to radiotherapy (75 mg/m²/die), then sequentially (200 mg/m²/die for 5 days in each cycle of 28 days, for 6 cycles).

The postoperative course was uneventful, the KPS was 80, but 18 months later she presented icterus. Serum tests revealed increased pathological levels of bilirubin and gGT. Abdominal CT scan demonstrated the presence of an hepatic mass, which was surgically removed. Histological examination confirmed the diagnosis of metastatic GBM. A whole-body CT scan did not reveal the presence of other metastatic lesions. A brain MRI performed 6 months later showed regrowth of the lesion, involving the deep structures. The patient died 2 months later (Table 1).

Case 3. A 67-year-old man underwent surgery with grossly total removal of a left frontal lobe GBM. He underwent adjuvant radiotherapy (64 Gy in 6 weeks using Linac) and adjuvant chemotherapy with temozolomide, first concomitantly to radiotherapy (75 mg/m²/die), then sequentially (200 mg/m²/die for 5 days in each cycle of 28 days, for 6 cycles). He had a stable postoperative course and no other clinical events for 19 months, with a KPS of 80.

After this period, he experienced a pain which irradiated to the right arm. CT scan demonstrated the presence of a lesion in the right humerus that was removed by surgical excision. The histologic diagnosis was GBM metastasis. Whole-body CT scan did not report other different metastases. Eight months later, the original tumor showed regrowth with progression to deep structures, and the patient died after 3 months (Table 1).

Case 4. A 72-year-old man was admitted for a right occipital GBM (Figures 3-6), and a grossly total excision was performed (Figures 7-8). He underwent adjuvant radiotherapy (64 Gy in 6 weeks using Linac) and adjuvant chemotherapy with temozolomide, first concomitantly to radiotherapy (75 mg/m²/die), then sequentially (200 mg/m²/die for 5 days in each cycle of 28 days, for 6 cycles). His clinical situation remained stable as the MRI follow-up confirmed, with a KPS of 80. However, 21 months later he developed hemoptysis and cough, which was studied by a thoracic CT scan. A neoplastic lesion was found in the left lung (Figures 9 A-B). A lobectomy was performed, and histology showed the features of a GBM metastasis. Whole-body CT scan did not reveal other metastases. After 7 months his clinical conditions worsened because of brain tumor regrowth involving important deep structures. The patient died 3 months later (Table 1).

Case 5. A 63-year-old man was treated by grossly total resection of a right temporal lobe GBM. He underwent adjuvant radiotherapy (64 Gy in 6 weeks using Linac) and adjuvant chemotherapy with temozolomide, first concomitantly to radiotherapy (75 mg/m²/die), then sequentially (200 mg/m²/die for 5 days in each cycle of 28 days, for 6 cycles). The postoperative course was uneventful with no other clinical manifestations for 19 months, with a KPS of 80. After this period, he began to experience hemoptysis and cough. A thoracic CT scan demonstrated a neoformation in the apical pulmonary lobe. The patient underwent a lung lobectomy, and the histological diagnosis was a GBM repetition. Whole-body CT scan did not show any metastatic lesions in other tissues. Eight months later, the original tumor had regrown and reached important deep structures. The patient died in only 2 months (Table 1).

Case 6. A 70-year-old woman required radical surgical removal of a right frontal GBM. The woman underwent adjuvant radiotherapy (64 Gy in 6 weeks using Linac) and adjuvant chemotherapy with temozolomide, first concomitantly to radiotherapy (75 mg/m²/die), then sequentially (200 mg/m²/die for 5 days in each cycle of 28 days, for 6 cycles). Her overall condition remained unchanged for 20 months, with a KPS of 80. After this period, a tumefaction appeared in the lateral-cervical lymph nodes. A biopsy subsequently showed metastatic GBM. Whole-body CT scan did not show any other tumor lesions.

A tumor regrowth in the frontal region made a second craniotomy necessary. The excision was grossly total, but after 8 months, deeper structures were involved. The patient died 2 months later (Table 1).

Case 7. A 69-year-old man was admitted for the surgical treatment of a cerebral tumor localized in the right temporal lobe. A grossly total excision was performed, and the diagnosis established the presence of a GBM. The man underwent adjuvant radiotherapy (64 Gy in 6 weeks using Linac) and adjuvant chemotherapy with temozolomide, first concomitantly to radiotherapy (75 mg/m²/die), then sequentially (200 mg/m²/die for 5 days in each cycle of 28 days, for 6 cycles). Postoperatively, there were no complications; KPS was 80. After a period of 23 months, the patient manifested hemoptysis and cough. Thoracic CT scan showed a pulmonary lesion in the apical area of the left lung. The whole pulmonary lobe was surgically removed. The histological diagnosis was GBM metastasis. A whole-body CT scan did not show any other metastatic lesions.

The right temporal lobe was again involved by tumor regrowth, which was treated by a second craniotomy and a new surgical removal. Nine months later the tumor showed progression to deep structures, and exitus occurred after 3 months (Table 1).

Literature review

In the English literature, to the best of our knowledge, 128 cases of extra CNS metastases from GBM have been reported, including our series (Table 2^{1,2,4,5-14,25-99}). Of these, we know the age of 127 patients, the sex of 123, and the survival of 103. There were 82 males and 41 females (M/F ratio, 2: 1). The average age at GBM diagnosis was 40 years (range, 3-74; Table 3). The mean overall survival was 17 months (range, 1-60; Figure 1). Twenty-one cases were reported from 1928 to 1967, and 107 from 1968 to 2006 (Table 3).

Table 2 - Division of the patients according to the period of diagnosis (1928-1967 and 1968-2006), sex and age

		Total period (1928-2006)	Period 1 (1928-1967)	Period 2 (1968-2006)

No. of cases		128	21	107
Sex	Male	67%	57%	69%
	Female	33%	43%	31%
Mean	age, yr	40 (range, 3-74)	34 (range, 6-61)	42 (range, 3-74)

Table 3 - Literature review of studies of extra central nervous system metastases from glioblastoma multiforme

Case No.	Investigator(s)	Patient’s age, sex	Site	Survival from primitive GBM (mo)

1	Davis¹	31, F	R Arm, L lung, R scapula, ribs	8
2	Kohlmeier²⁵	38, M	Lung, pleura	12
3	Brandt²⁶	53, M	Lung, kidney	24
4	Nowotny²⁷	33, F	L retroauricular and cervical lymph nodes	21
5	Cross²⁸ and Cooper Case 2 (1958)	20, M	Lungs, orbit, abdominal wall	9
6	Zeitlhofer²⁹	40, F	Retroauricular and cervical. Lymph nodes	60
7	Wolf³⁰	14, F	Lungs, pleura, ribs, vertebra, sternum, mediastinum,	13
			para-aortic lymph nodes
8	Gropp³¹	48, M	Heart (R ventricle)	1
9	Bogdanovich³²	61, F	Lungs	6
10	Dewart³³ or Thiry³⁴	57, F	Liver	>60
11	Ehrenreich³⁵ or Feigin case 8 (1958)	44, M	R Lung	10
12	Feigin³⁶ case 12 (1958)	6, M	L Lung	15
13	Garret³⁷	55, F	Cervical lymph nodes	10
14	Giok³⁸	25, F	Lungs	33
15	Grampa³⁹	40, M	L kidney	7
16	Brodskaia⁴⁰	24, M	L supraclavicular and cervical lymph nodes	10
17	Ley⁴¹ case 2 (1961)	22, M	Cervical lymph nodes	33
18	Labitzke⁴² or Smith case 9 (1969)	21, M	Lung, paratracheal, hilar and cervical lymph nodes	21
19	Nigogosyan⁴³ case 1 (1962)	40, M	Lungs, vertebra, sternum, lymph nodes	14
20	Schejbal⁴⁴	9, F	R cervical lymph nodes	19
21	Wisiol et al.⁴⁵	31, M	Vertebra, acetabula	20
22	Smith⁴⁶ case 1 (1969a)	52, M	Lung, mediastinal lymph nodes	60
23	Smith⁴⁶ case 2 (1969a)	38, M	Hilar lymph nodes	9
24	Smith⁴⁶ case 3 (1969a)	24, M	Lung	18
25	Smith⁴⁶ case 4 (1969a)	43, M	Liver	6
26	Smith⁴⁶ case 5 (1969a)	45, M	Liver	6
27	Smith⁴⁶ case 6 (1969a)	6, M	L lung	7
28	Smith⁴⁶ case 7 (1969a)	58, M	Liver	6
29	Smith⁴⁶ case 8 (1969a)	29, M	Lung, periaortic and cervical lymph nodes	10
30	Smith⁴⁶ case 10 (1969a)	55, M	Ribs	13
31	Smith⁴⁶ case 11 (1969a)	54, M	Lung	8
32	Smith⁴⁶ case12 (1969a)	45, M	Cervical lymph node	21
33	Smith⁴⁶ case13 (1969a)	36, M	Vertebrae, acetabulum	12
34	Smith⁴⁶ case14 (1969a)	63, M	Lung, liver, adrenal gland	1
35	Smith⁴⁶ case15 (1969a)	44, M	Liver	8
36	Smith⁴⁶ case 16 (1969a)	49, M	Liver, pancreas, cervical lymph nodes, sternum	16
37	Smith⁴⁶ case 17 (1969a)	42, M	Lungs, cervical lymph nodes	50
38	Smith⁴⁶ case 18 (1969a)	63, F	Lungs, vertebrae	11
			(T10-11)
39	Smith⁴⁶ case19 (1969a)	42, F	Cervical lymph node	8
40	Smith⁴⁶ case 20 (1969a)	38, M	Lung, pleura, hilar lymph nodes	20
41	Smith⁴⁶ case 21 (1969a)	36, F	Ribs, vertebrae, cervical and mediastinal lymph nodes	13
42	Smith⁴⁶ case 22 (1969a)	64, M	Liver, lung	10
43	Smith⁴⁶ case 23 (1969a)	36, M	Vertebrae	14
44	Anzil⁴⁷	54, F	Liver, vertebra (T11)	13
45	Dalla Pria⁴⁸	40, F	R arm, R. haunch	2
46	Dalmer⁴⁹	39, M	Cervical lymph nodes	6
47	Wakamatsu^50,51	22, M	R lung, pleurae, pericardium, diaphragm	9
48	Komatsu^52,53	18, F	L cervical lymph nodes	7
49	Dolman⁵⁴	35, F	L intraparotid lymph nodes	3
50	Johnson⁵⁵	46, M	Lungs, hilar lymph nodes, liver	36
51	Nikkanen⁵⁶	12, F	Lungs, skeleton, cervical lymph nodes	7
52	Yao⁵⁷	18, M	Lung, thyroid gland, neck, paratracheal
			and mediastinal lymph nodes	19
53	Hulbanni⁵⁸	63, M	R lung, bronchial lymph nodes,vertebra	2
54	Montaut⁵⁹ case1 (1976)	23, M	Lungs, liver, cervical lymph nodes	14
55	Schuster⁶⁰ case 6 (1976)	20, M	L cervical lymph nodes	17
56	Schuster⁶⁰ case 7 (1976)	55, M	R cervical lymph nodes	18
57	Russell⁶¹	25, M	Lungs, pleurae, pericardium, L. pulmonary hilar lymph nodes	>60
58	Russell⁶¹	70, F	Pleurae, pericardium	6
59	Russell⁶¹	3, F	Lungs, pleurae, pulmonary hilar lymph nodes	31
60	Russell⁶¹	7, F	Liver, adrenal medulla, hilar lymph nodes, pleurae, vertebra	NA
61	Russell⁶¹	16, F	R Pleurae, peritoneum, diaphragm, lumbar region	36
62	O’Connor⁶²	53, F	L supraclavicular lymph nodes, pleura	7
63	Terheggen⁴	12, M	Bone marrow, pubic and ischiac bones, L ileum	10
64	Pasquier⁶³	21, F	Liver, L submandibular lymph nodes	NA
65	Slowik⁶⁴ case 1 (1980)	35	Bones, soft tissues, sinus vertebrae	20
66	Slowik⁶⁴case 2 (1980)	35	Bones, soft tissues, sinus vertebrae	20
67	Slowik⁶⁴ case 3 (1980)	35	Bones, soft tissues, sinus vertebrae	20
68	Slowik⁶⁴ case 4 (1980)	35	Bones, soft tissues, sinus vertebrae	20
69	Mousavi⁶⁵	55, F	Bone marrow, liver	4
70	Dietz⁶⁶	24, M	Thoracic vertebrae, sternum	6
71	Yung⁶⁷ case 1 (1983)	57, M	Bone marrow, L femur, R sacroiliac joint, ribs, R humerus, pleura	NA
72	Yung⁶⁷ case 2 (1983)	24, F	Bone marrow	10
73	Sadik⁶	48, M	Lumbar vertebra	NA
74	Steinbok⁶⁸	27, F	Cervical lymph nodes	22
75	Wakabayashi⁶⁹	43, M	Peritoneal cavity	NA
76	Yokoyama¹⁴	22, F	Hilar lymph nodes, lung, pleura, sternal bone marrow, liver	4
77	Ogata A⁷ ⁰	68, M	Lungs, bronchial lymph nodes, liver, kidney, heart, spleen	8
78	Trattnig S⁷¹	29, M	Cervical lymph nodes, bones	NA
79	Gamis²	11, F	Thoracic bones, humerus, calvarium, facial bones, mandible,
			femurs, tibias, pelvis, shoulders, manubrium, L iliac crest,
			ankles, L foot	6
80	Newton⁷² case 1(1992)	13, M	Peritoneal cavity, omental	NA
81	Newton⁷² case 2 (1992)	9, F	Peritoneal cavity, omental	NA
82	Zappia⁷³	39, M	Submandibular, jugulodigastric, deep cervical,
			parotid chains lymph nodes	NA
83	Malca⁷⁴	46, M	Thoracic, lumbar and sacral vertebrae, ileum, femur, ribs, pleurae	27
84	Chesnut⁷⁵	42, M	Cervical vertebrae	14
85	Gonzales Campora⁷⁶	47, M	Cervical and supraclavicular lymph nodes	12
86	Minami⁷⁷	9, M	Meninges, spinal metastases	NA
87	Mihara⁷⁸	35, F	Vertebra (T1)	14
88	Shuto⁷⁹	42, F	Liver, skull	NA
89	Granjon⁸⁰	50, M	Parotid gland, lung, pleura, endobronchial masses	7
90	Jonas⁸¹	48, F	Liver	4
91	Vural, Hagmar⁸ case 1 (1996)	40, M	R side of neck	47
92	Wallace⁹ case 1 (1996)	41, M	Neck, cervical and supraclavicular lymph nodes,
			extraocular muscle, R eye	NA
93	Wallace⁹ (1996) case 2	39, M	R orbit, preauricular lymph nodes	7
94	Al-Rikabi⁸²	4, M	L cervical lymph nodes	NA
95	Fecteau⁸³	18, F	Omentum, stomach, abdominal wall, pelvis	NA
96	Greif⁸⁴	51, M	Pleurae, lungs, liver	7
97	Datta⁸⁵	35, F	R cervical lymph nodes	10
98	Waite⁸⁶	40, M	L parotid region	>24
99	Frappaz⁸⁷	52, M	L ribs, lumbar vertebra, R lung	12
100	Widjaja⁸⁸	58, M	Liver, spleen	NA
101	Beauchesne⁷	54, M	Dorsolumbar vertebrae, iliac bone, lung, heart	10
102	Park¹² case 1 (2000)	31, M	Vertebrae, humerus	4
103	Park CC, Hartmann C	31, M	Neck, pelvis	7
	et al.¹² case 2 (2000)
104	Park¹² case 3 (2000)	27, M	R lung	7
105	Park¹² case 4 (2000)	25, F	Parotid gland, neck	21
106	Park¹² case 5 (2000)	60, M	Hip, cervical vertebrae	21
107	Laraqui⁸⁹	40, M	Lung, endobronchial masses	NA
108	Hata N⁹⁰	NA	Lung, lymph nodes	NA
109	Kuhn⁹¹ case 2 (2003)	58, M	R parotid gland	NA
110	Yasuhara¹⁰	47, F	Spleen, lung	6
111	Ueda¹³	42, M	Cervical lymph nodes, thoracic vertebrae, L clavicle, epicardium,	NA
			R kidney, pancreas, liver, L cervical and auricle soft tissue
112	Erdem⁹²	37, F	Infratemporal fossa, R orbit, lateral and medial pterygoid	NA
			muscles, R carotid artery
113	Fabi⁹³	43, M	Lumbar vertebrae (L1,L3)	NA
114	Montagne⁹⁴	74, M	Vertebrae, lungs, mediastinal lymph nodes	3
115	Utsuki⁵	42, M	Axis	>36
116	Chivukula⁹⁵	62, M	R lung	NA
117	Mirzayan¹¹	30, M	Bones (lumbar and thoracic vertebrae),	NA
			L 7^th costovertebral junction, nodal, paravertebral
			and mediastinal metastases
118	Tuominem⁹⁶	25, M	Mediastinum	61
119	Taha⁹⁷	33, M	Parotid gland, cervical lymph nodes	NA
120	Rajagopalan⁹⁸	60, M	Lumbar and sacral vertebrae, epidural soft tissue	NA
121	Didelot⁹⁹	74, M	Bone marrow, lung, mediastinal lymph nodes	3
122	Piccirilli case 1 (2006)	66, M	Lung	25
123	Piccirilli case 2 (2006)	74, F	Liver	26
124	Piccirilli case 3 (2006)	67, F	Humerus	30
125	Piccirilli case 4 (2006)	72, M	L lung	31
126	Piccirilli case 5 (2006)	63, M	Lung	29
127	Piccirilli case 6 (2006)	70, F	Cervical lymph nodes	30
128	Piccirilli case 7 (2006)	69, M	Lung	35

R, right; L, left; NA, not available.

The mean age in the first period (i.e., 1928-1967) was 34 years (range, 6-61) and in the second period, 42 years (range, 3-74; Table 3). The sex distribution was 12 males and 9 females in the first and 70 males and 32 females in the second period (Table 3). The mean survival in the first was 19 months and in the second period, 16 months (even though these values were not statistically relevant, logrank, 0.417) (Figure 2).

Discussion

GBM is a highly malignant primary brain tumor. According to the characteristic behavior of these neoplasms, the occurrence of extracranial metastases is a very uncommon event, with a reported frequency in the literature of less than 2%³. Several attempts have been made to explain the rarity of extraneural metastases. Neidhart et al.⁴ described the following six reasons: the absence of lymphatic vessels in the CNS, intracranial perivascular spaces do not communicate with extracranial fluid space, the connections between the subarachnoid space and extracranial lymphatic vessels are very sparse, intracerebral veins are thin walled and would probably collapse from compression before a tumor’s penetration^4-6, meningeal tumors grow on the dura mater but remain only on the surface, dural veins are protected by a dense connective tissue^4,6.

GBM has a poor prognosis and presents an average survival time of approximately 1 year^3,7. Extracerebral metastases usually occur in regional lymph nodes (51%), particularly in the cervical group, in lungs and pleura (60%), and in the skeleton (31%), where vertebral bodies are the most involved. Bone metastases from GBM can be differentiated in lytic or sclerotic lesions on neuroimaging, and they are usually seen as a multiple extracranial spread. Only particular cases present an isolated vertebral localization (i.e., axis)⁵. Other target tissues for metastases are the liver (22%), the operative flap, dural veins, meninges, the scalp, the kidney, the orbit⁴, the spleen⁵, and the heart⁷.

The tumor is able to use several routes to metastasize, anad we can describe five main ways⁴: hematogenous spread via the vessels of the primary tumor, hematogenous spread after tumor invasion of the dural veins, hematogenous and/or lymphogenous spread after infiltration of the skull and extracranial soft tissues, spread via the cerebrospinal fluid, spread via ventriculoatrial or ventriculo-pleural shunts.

Hematogenous and/or lymphogenous spread after infiltration of the skull and extracranial soft tissues represents the most common route, above all in patients who have undergone a surgical intervention. In fact, the operation alters the brain anatomy and gives the tumor the possibility to reach the extracranial soft tissue and to gain access to blood or lymphatic vessels. This is the main reason why so many different metastases to lymph nodes have been demonstrated^4,8,9. The hematogenous system is the preferential way involved in lung, osseous and spleen metastases. When the vertebrae are involved, the glioma cells probably enter the Batson plexus (which is situated in the anterior lumbar cord) and disseminate in the cerebrospinal fluid. The capacity of the Batson plexus to give blood to the inferior vena cava and also to lumbar and sacral vertebrae allows the formation of metastases in the lung and liver and in the lumbar and sacral vertebrae⁵.

Hematogenous spread can follow particular vein connections: this is the case of the axis metastasis. According to Utsuki et al.⁵, there could be some connections between part of the meningeal venous system and craniocervical venous system, which is connected to the internal vertebral venous plexus. The internal vertebral venous plexus flows back to the anterior and posterior surface of the cervical vertebrae, and there is also blood flow to the body of the axis⁵.

The so-called “drop metastases”, due to metastatic dissemination with drainage of the CSF, as well as for the placement of ventricular systemic shunts¹⁰, are a well-documented event^4,11, but tumor expansion through the cerebrospinal circulation remains an unusual way.

Various hypotheses have been made to find a pathogenesis for the metastasis phenomenon. Interesting considerations surely derive from Park et al.¹². They suggested that the metastatic potential of GBM might be correlated with particular molecular features, P53 gene mutations and differential clonal selection^3,12,13. In fact, some metastases arise from genetically altered subclones of the primary tumor. Several biological and molecular studies¹³ have closely examined the different patterns of genetic expression between the primary tumor and some metastatic samples, using the cDNA microarray technique. They showed the following common results in both: the overexpression of insulin growth factor and a decrease of DNA-PK genetic expression, which is a DNA-dependent protein kinase involved in DNA repair mechanisms. The first probably plays a role in tumor progression; the second contributes to the malignant transformation of the glioma.

In other words, the present study underlines the similar patterns of genetic expression in intracranial tumors as well as in metastases, suggesting that distant dissemination is the consequence of direct infiltration of tumor cells into extracranial blood vessels¹³.

An alternative explanation for the major tendency to metastasize is related to the appearance of a sarcomatous component in the original glioblastoma^10,14. In fact, we know that the gliosarcoma can metastasize more easily than other malignant gliomas. Moreover, patients with extracranial metastases from GBM with a sarcomatous component have a worse prognosis than patients with other gliomas. Most of the previously reported cases did not present a sarcomatous component in the early state, so it is thought that adjuvant radiotherapy and chemotherapy may have caused changes in the histological features¹⁰. All our patients presented a primary GBM and none of them showed a sarcomatous component after the histological examination. All of them received adjuvant radiotherapy and chemotherapy, but most of them did not undergo a second surgical removal of the brain lesion, which allowed us to verify histologically if a sarcomatous transformation took place. The only two patients who underwent a second surgical approach at the brain did not present any sarcomatous cells. Moreover, histological examination of metastatic GBM did not report any sarcomatous elements.

In relation to a study of 1977¹⁵, some authors examined the different immunologic responsiveness of GBM to several antigens in long- and short-term survivors. The experiments demonstrated at the beginning an anergic reaction, but after a relative short period, a progressive increase in immune responsiveness in all tests performed in vivo and in vitro. This last event probably represents a host immune attempt to arrest tumor proliferation. This is only a transitory phase for the short-term survivors but represents the expression of a different immunogenetic pattern for the long-term survivors. In fact, particular antigens were present only in the cells of the long-term survival glioblastoma and were not seen in short-term survival GBM material. In the same way, a meningioma-related dicentric chromosome marker appeared only in the cells of long-surviving glioblastoma patients. Another important consideration derives from the comparison of PAGE (polyacrylamide gel electrophoretic) separation of serum: in fact, between their long- and short-surviving patients there was a significant quantitative difference in the measurement of two prealbumin components, and the a1-acid glycoprotein/prealbumin ratio gave a sensitive index of the degree of malignancy¹⁵.

The elderly age of our patients is another important point of discussion. In fact, several authors have confirmed a growing incidence of tumors in elderly patients^16-19. In particular, a study conducted in France between 1983 and 1990^16,18 showed an increase of 5% per year in the incidence of malignant astocytomas in the population over 65 years of age. We also have to consider the great increase in life expectancy of the population of industrialized countries. This fact probably created a large potential target sample for this neoplasm¹⁸. The increasing incidence of primary and malignant brain tumors seems to be specific in elderly patients^18,19, and this observation can only partially be attributed to the extensive use of new diagnostic neuroimaging like MRI and CT.

Elderly patients with a diagnosed GBM may often present a concomitance of important diseases such as diabetes, chronic broncho-pulmonary disease, ischemic heart disease, and hypertension. These factors can determinate a shorter survival. The other situations characterized by a poor survival in elderly patients without such diseases can be explained by a less aggressive multimodality treatment that the neurosurgeon chooses for the lower KPS generally observed in elderly patients^18,20,21. Some studies, only in particular cases, have evidenced that multimodality treatment could be less effective in elderly patients for the presence of specific mutations able to render tumor cells more resistant to adjuvant chemotherapy (p-53 mutations)^18,22 and radiotherapy (deletions in chromosome 10)^18,23.

These considerations persuaded us to perform macroscopically complete surgical debulking, according to the concept that if the extent of the surgical removal is greater, the outcome is better for the patient^18,24. In fact, radical removal of GBM through an aggressive approach can delay tumor recurrence and reinforce the effect of adjuvant therapy. For these reasons, according to our experience, elderly patients, in a good functional state of health, should be treated in the same way as younger patients with the same diagnosis¹⁸.

In the past, the mean survival time of a patient with GBM did not exceed 6 months, but today this time can reach and also surpass 2 years. Our patients had an average survival time of 29 months (range, 25-35), although they were all elderly patients. Such a long survival time shows that the chosen treatment was appropriate for these patients.

Metastasis always preceded regrowth of the primary GBM (mean value, 7 months; range, 6-9). Nevertheless, in each case death was the result of cerebral GBM regrowth involving important deeper structures. Although the literature confirms the scarce tendency to metastasize, we have to report an important documented increase. In the 40 years between 1928 and 1967 in the literature, 21 cases of GBM extra-CNS metastases were reported, whereas in the 39 years between 1968 and 2006 there were 107 cases, about five times more. Advances in the multimodality treatment of gliomas, the earlier diagnosis due to a wide diffusion and improvement in neuroimaging techniques, and the subsequent longer patient survival may partially justify the growing incidence of extracranial metastases, from the value of 0.44%, reported by Smith et al. in 1969², to the present value of 2%³.

This phenomenon may also depend on the potential modification of the histological and genetic features of primary GBM. This new aspect adds another conditioning element to the GBM prognosis: metastasis treatment.

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cancer bleeding control
Cancer care facilities
cancer centre
cancer chemotherapy
cancer complication
cancer control
cancer control-planning
cancer cytogenetics
cancer diagnosis
cancer in spouses
Cancer incidence
cancer metastasis
Cancer mortality
Cancer pain
Cancer pain treatment
cancer prevalence,
cancer prevention
Cancer proteomics
Cancer registries
Cancer registry
cancer research
cancer research infrastru
cancer survival
Cancer therapy
cannabinoid receptor-1 ge
Capecitabine
capecitabine monotherapy
Capillary leak syndrome
carbon ion radiotherapy
carbon nanotubes
Carboplatin
Carcinoids
Carcinoma
Carcinoma erysipelatoides
Carcinomatosis
Carcinosarcoma
cardiac angiosarcoma
Cardiac dysfunction
Cardiac metastases
cardiac sarcoma
cardiac toxicity
cardiopulmonary bypass
Cardiotoxicity
carotid body tumor
carotid femoral and aorti
Case report
case-control studies
Case-control study
caspase-6
caspase-9
Castleman's disease
cathepsin
Cathepsin D
Catheters
caveolae
Cavernous hemangioma
cavernous liver angioma
CCEA
CCNU
CD-138
CD10
CD105 (endoglin)
CD117
CD34
CD4+
CD40
cd40 ligand
CD40L
CD44
CD8+
CD8+ T cell
CD99
CDX-2
Celiac disease
Celiac plexus block
cell cycle
cell cycle proteins
cell death
cell invasion
cell migration
cell proliferation
cell toxicity
Cell types related marker
cell-specific magnetic re
cellular therapy
Central nervous system pr
central venous devices
Cerebellar metastasis
cerebral meningioma
Cervical cancer
Cervical cancer epidemiol
Cervical carcinoma
cervical chordoma
Cervical dysplasia
Cervical intraepithelial
cervical intraepithelial
cervical node metastasis
cervical plexus
cervical squamous cell ca
Cervix
cetuximab
Changes in molecular biol
Chemoprevention
Chemoradiation
Chemoradiotherapy
Chemotherapy
Chemotherapy at the end o
chemotherapy toxicity
chemotherapy-induced
chemotherapy-induced naus
Chemotherapy-induced peri
Chest reconstruction
Childhood
Childhood cancer
children
China
cholesterol
Chondrosarcoma
Chordoma
Chorioallantoic membrane
Choroidal metastasis
Chromogranin A
chromogranin-A
Chromosomal aberration
chromosome 3
chronic leukemia
chronic myeloid leukemia
Chronomodulated infusion
Chronotherapy
chylous ascites
Cigarette smoking
CIN
Ciplatin
cirrhosis
Cisplatin
Cisplatin-resistant metas
CK 5/6
classic Kaposi’s sarcom
Classification
clear cell renal carcinom
Clinic-pathological aspec
Clinical and pathological
Clinical audit
Clinical features
Clinical indications
clinical indicators
Clinical practice
Clinical stage
clinical stage I
Clinical staging
Clinical trial
Clinical trials
Clonality
Clozapine
CMF
CMF regimen
co-culture
CO2 laser
coagulation
Cohort studies
Cohort study
Cohort stuudies
collecting duct carcinoma
Colo-anal anastomosis
Colon
Colon adenocarcinoma
Colon cancer
Colon carcinoma
colon carcinoma metastasi
Colon metastases
Colonic adenocarcinoma
Colonoscopy
color Doppler sonogram
colorectal
Colorectal adenocarcinoma
Colorectal cancer
colorectal cancer liver m
Colorectal carcinoma
Colorectal neoplasms
colorectal screening
colorectal surgery
Colorectal tumor
Colorectal tumors
colposcopy
combined chemoradiotherap
Combined modality therapy
Combined modality treatme
Combined therapy
combined tumor
Combined-modality treatme
Comet assay
commissioning
common diagnostic pitfall
communication
communication of bad news
comorbidity
comparative genomic hybri
Comparative studies
Competitive PCR
complementary medicine
Complete response
Complications
composite hemangioendothe
comprehensive geriatric a
comprehensiveness
Computed tomography
computed tomography (CT)
computer-assisted reading
Computerized tomography
concomitant
concomitant boost
concomitant radiochemothe
CONCORD
Concurrent boost radiothe
Concurrent chemo-radiothe
concurrent chemoradiother
Conflict of interest
conformal boost
conformal external beam r
Conformal radiotherapy
congenital breast malform
Conization
conservative management
Conservative radiotherapy
Conservative surgery
Conservative treatment
consolidation chemotherap
continuous 5-fluoruracil
Continuous infusion
Contrast enhancement
coordination
Cordoba
Core biopsy
core needle biopsy
Coronary ostial stenosis
Correct sun exposure
cosmesis
Cosmetic results
cost
cost-effectiveness
cotyledonoid dissecting l
cox-2
coxofemoral arthrodesis
CpG island methylation
Cranial metastases
cranial trauma
craniospinal irradiation
cribriform carcinoma of t
cricoid cartilage
cricoid tumor
Croatia
cross-talk
Crude rates
Cryoglobulinemia
Crystal-storing histiocyt
CT
cultural diversity
Curettage mastectomy
Cushing's syndrome
Cutaneous melanoma
cutaneous tumors
cyberKnife
cyclooxygenase-2
cyclophosphamide
cyst
cystadenocarcinoma
cystatin
cystectomy
Cystic components
cystic hygroma
cystic lymphangioma
Cystic mesothelioma
cystic neuroendocrine pan
Cystoprostatectomy
cytarabine
Cytogenetic analysis
Cytogenetic biomarkers
cytogenetics
Cytokine
Cytokines
cytology
Cytomegalovirus
Cytoreduction
Cytoreductive surgery
Cytotoxic granules
cytotoxic T lymphocytes
dacryocystitis
DAPI
DAPk
Daunorubicin
De novo
de novo colon cancer
dead children
Deep venous thrombosis
Delayed onset
delays in diagnosis
Delivery
Dendritic cells
Dendritic cells inflammat
dental factors
Depression
Dercum’s disease
dermatofibrosarcoma protu
Dermoid cyst
Dermoscopic diagnosis
Dermoscopy
Desmoid tumor
Desmoid tumors
desmoplastic small round
Desmoplastic small round-
Desmoplastic tumor
detergent resistant micro
dexrazoxane
DFMO
diabetes
diabetes insipidus
Diagnosis
diagnosis disclosure
diagnostic imaging
diagnostic laparotomy
diagnostic odds ratio
dialysis
Diet
Dietary questionnaire
differential diagnosis
Differentiated thyroid ca
Differentiated thyroid ca
Diffuse gastric cancer
diffuse large B-cell lymp
Dihydrotestosterone
Diplopia
Discomfort
disease management
disease progression
disease-free period
disease-oriented bioban
disseminated intravascula
distance education
Distant metastases
DNA
DNA binding
DNA damage
DNA methylation
DNA microarrays
DNA ploidy
DNA repair
DNA sequencing
docetaxel
Dose calculation algorith
Dose fractionation
dose intensification
dose-dense chemotherapy
dose-finding study
dose-intense
Dose-intensity
Dose-volume histograms
Dosimetric calibration
dosimetric variation
Down syndrome
Down-staging
downdose
Doxorubicin
Doxycycline
DRAK1
Drinking habits
drug delivery
Ductal adenocarcinoma
Ductal carcinoma in situ
Ductopenia
duodenal
Duodenal neoplasm
Duodenocephalo-pancreasec
duodenum
Dural involvement
duration of treatment
DVL1
dynamic micro-multileaf c
dysphonia
dyspnea
Dysproteinemia
E-cad
E-cadherin
E-selectin
Early breast cancer
Early cancer
Early diagnosis
early gallbladder carcino
Early glottic carcinoma
Early polypoid colorectal
early rectal cancer
early stage
Early stage lung cancer
early technology assessme
eccrine mucinous adenocar
Ecological monitoring
Ectopic
ectopic breast
Ectopic pregnancy
Edema
Educational level
Educational message
EGFR
eLAV-like protein
Elderly
elderly cancer patients
elderly patient
Elderly patients
elective nodal irradiatio
electrocardiogram
electrochemotherapy
electromagnetism (EM)
electromyography
electronic chart
electroporation
Embolization
Emergency surgery
en bloc resection
Encephalopathy
end of life
End-of-life care
end-stage renal impairmen
endocrine system
Endodermal sinus tumor
endoG expression
endogenous porphyrins
Endometrial cancer
Endometrial carcinoma
endometrial tumor
Endometrium
Endoscopic ablation
endoscopic removal
endoscopy
Energy expediture
Engineered tumor cells
Enhancement
Enoxaparin
enteric nervous system
enterocutaneous fistula
Environmental exposure
Environmental pollution
Environmental tobacco smo
EORTC questionnaire
ependymomas
EPIC
epidemiologic methods
Epidemiology
epidermal growth factor
epidermal growth factor r
Epigenetic alterations
Epigenetics
Epirubicin
epithelioid
Epithelioid sarcoma
Epo
Epoetin alfa
Epstein-Barr virus
Epstein-Barr virus (EBV)
ER
era
erB-2
erlotinib
errors in radiation deliv
erythroleukoplakia
Erythropoietin
Esophageal adenocarcinoma
Esophageal cancer
Esophagogastroscopy
Esophagus
esophageal cancer
esthesioneuroblastoma
estrogen receptor
estrogen-progesterone rec
Ethics
Ethics committees
Ethmoid cancer
Ethnic distribution
European Union
euthanasia
event tree model
evidence-based medicine
Ewing sarcoma
Ewing's sarcoma
Ewing’s sarcoma
Ewing’s sarcoma family
exemestane
Exercise testing
exonic splicing enhancers
exosomes
experimental
extended cholecystectomy
External beam radiotherap
Extra-abdominal metastasi
Extracapsular extension
Extracellular matrix prot
Extradonal non-Hodgkin's
Extragonadal germ cell tu
extramedullary plasmacyto
Extranodal lymphoma
extranodal MALT lymphoma
Extraosseous Ewing's sarc
extraosseous sarcoma
Extrapulmonary small cell
Extravasation
eyelid
ezrin
facial nerve
false positive
Familial adenomatous poly
Familial polyposis
families
family
Fas/FasL
fatigue
FDG-PET
feasibility
febrile neutropenia
Female
fetal dose
FHIT gene
Fibroma
fibromatosis
fibronectin
fibrosis
filgrastim
Finasteride
fine-needle aspiration cy
FISH
Fistula
fixed-dose-rate infusion
FLIPI
Floxuridine
fluorescence
Fluoropyrimidine-pretreat
Fluorouracil
FMF
focal adhesion kinase
Focal nodular hyperplasia
folate
FOLFIRI
folfox
FOLFOX IV/LV5FU2 chemothe
FOLFOX regimen
folinic acid
Follicular carcinoma
Follicular lymphoma
follicular thyroid cancer
follow-up
Food
Forearm
foregut neuroendocrine ca
Four or more positive axi
Fractionated stereotactic
fractionation
fraud
fullerenes
fulminant liver failure
G-CSF
galectin-1
galectin-3
Gallbladder
Gallbladder carcinoma
Gamma probe
Gamma-glutamyltransferase
gastrectomy
Gastric cancer
Gastric carcinoma
Gastric melanoma
gastric myoepithelial ham
gastrointestinal carcinoi
gastrointestinal interven
Gastrointestinal lymphoma
Gastrointestinal neoplasm
Gastrointestinal stromal
Gastrointestinal stromal
gastrointestinal stromal
gastrointestinal stromal
Gemcitabine
Gender differences
Gene expression
gene expression profile
gene polymorphism
gene therapy
General practitioners
Genetic research
genetic susceptibility
Genetic testing
Genetic tests
Genomic instability
genomics
genomics
GEP neuroendocrine tumors
germ cell tumor
germ cell tumors
Germline mutations
gestational trophoblastic
giant basal cell carcinom
giant follicles
giant keratoacanthoma
Giant mixed retroperitone
Giemsa
GIST
glioblastoma
Glioblastoma multiforme
Gliofibroma
Glioma
gliosarcomas
Glottic cancer
glucagon
glucose-6-phosphate dehyd
glutamine
glutathione S-transferase
glycoproteins
Gonadoblastoma
good clinical practice
Good's syndrome
GPI
granular cell tumor
granulocyte-colony stimul
granulocytic sarcoma
Granulomatous angiopannic
Granulomatous gastritis
Graves' disease
growth inhibitory peptide
growth rate
GSTP1
guidelines
Guillain-Barré syndrome
Gynecomastia
Gynecomastia and hormone
Gynecomastia and prostate
H. pylori
Hadron therapy
hairy cell leukemia
half-body irradiation
hamartoma
Hand-foot syndrome
Hashimoto’s thyroiditis
HBV/HCV infections
HCV
HDR brachytherapy
Head and neck
Head and neck cancer
Head and neck carcinoma
Head and neck malignancie
head and neck neoplasms
head and neck tumor
Head trauma
Health-related quality of
healthy donors
Heart
heart failure
heart transplantation
heat
heat shock protein 70
heavily pretreated
Hemangioendothelioma
Hemangiopericytoma
Hemangiosarcoma
Hematological malignancie
hematological malignancy
Hematopoietic stem cell t
hematuria
Hemodialysis
Hemoglobin levels
hemoperitoneum
hemophilia A
Hep-2 cells
Heparin
Hepatic adenosquamous car
Hepatic arterial infusion
Hepatic arterial infusion
Hepatic artery
hepatic tumor
Hepatitis B virus
hepatitis B virus (HBV)
Hepatitis B virus integra
Hepatitis C virus infecti
hepatoblastoma
Hepatocellular
Hepatocellular carcinoma
hepatocellular carcinoma
hepatocyte growth factor
HER-2
HER-2 receptor
HER-2/neu
HER2
HER2-positive metastatic
Herceptin
Hereditary breast cancer
hereditary non-polyposis
HEY1
high dose
High dose chemotherapy
high dose rate
high genetic risk
high-dose boost
High-dose chemotherapy
high-dose epirubicin
High-dose rate brachyther
high-grade glioma
High-grade squamous intra
high-risk medulloblastoma
Histogenesis
histological diagnosis
Histological score
HIV
hMLH1
hMLH1 hypermethylation
HNPCC
Hodgkin disease
Hodgkin's disease
Hodgkin's disease (HD)
Hodgkin’s disease
Home palliative care serv
homocysteine levels
Horizontal growth phase m
Hormone receptor status
Hormone refractory
hormone replacement thera
Hormone therapy
Hormone-refractory prosta
Hormonorefractory
Hormonotherapy
Hospital
Hospital-based population
HPV
Hrthle cell carcinoma
hTERT
hu-PBL/SCID chimera
huge hepatocellular carci
Human
human carboxylesterase-2
Human chorionic gonadotro
Human Epo receptor (EpoR)
Human G-CSF receptor
Human immunodeficiency vi
Human papilloma virus
Human papillomavirus
human sarcoma
Human tumor cell lines
hur
hydration
hydrocele
Hydrogen peroxide
hydronephrosis
Hypercoagulable state
Hypereosinophilic idiopat
Hyperfractionated radioth
Hyperfractionation
Hyperparathyroidism
Hypersensitivity reaction
Hypertermic tissue ablati
hyperthermia
Hypocalcemia
Hypofractionation
Hypoparathyroidism
hypopharyngeal cancer
hypothyroidism
ICCC-3
ICD-10
Id2 protein
Idiopathic thrombocytopen
IFN-a-2a
Ifosfamide
IgR
IHH
IL-12
IL-2
ileal carcinoid
ileal mucosa
image analysis
image fusion
Image probing
image-guided intensity-mo
Image-guided radiotherapy
imaging
imatinib
Imatinib mesylate
imiquimod
immune host response
Immunity
immunocompetent host
immunocytochemistry
Immunodeficiency
immunohistochemical analy
Immunohistochemical marke
Immunohistochemistry
Immunoradiometric assays
Immunoscintigraphy
Immunotherapy
impact factor
Implantable port
IMRT
in vivo imaging
in vivo small animal magn
inappropriate doses of ch
incentives
Incidence
incidence rates
Independent studies
induced lymphoma
induction chemotherapy
induction therapy
infant
infantile myofibromatosis
infection
Infections
infectious agents
infiltrating ductal carci
Inflammation
Inflammatory bowel diseas
Inflammatory breast carci
Inflammatory mechanism
Inflammatory metastatic c
inflammatory myofibroblas
inflammatory pseudotumor
Informed consent
infrastructures
infusion reaction
Infusional chemotherapy
infusional therapy
Inguinal canal
Inguinal hernia
Inoperable bowel obstruct
insular
Insular thyroid carcinoma
Insurance
integral dose
Integrated radiotherapeut
integration
integrin beta 3
intensity modulated radia
Intensity-modulated exter
Intensity-modulated radia
Intensity-modulated radia
intensity-modulated radio
Interaction
Interactive computer grap
Interferon
interferon beta
Interleukin-2
Interleukin-6
interleukins
Intermediate emetogenic c
internal mammary node met
international collaborati
international cooperation
International Prognostic
internet
Interobserver agreement
Interpectoral (Rotter's)
interstitial pneumonitis
interval cancer
interval cancers
interval censoring
Interventional radiology
intestinal permeability
intestinal pouch
intima-media thickness
Intra-arterial chemothera
intra-operative radiother
Intraabdominal tumor mass
Intracranial tumors
Intraductal carcinoma
Intrahepatic cholangiocar
Intrahepatic cholestasis
intramedullary metastases
intramedullary tumor
intraoperative pathologic
Intraoperative radiothera
intraosseous hemangioma
Intraperitoneal chemother
intraperitoneal chemoth
Intraperitoneal hyperther
intratumoral lymphocyte
Intravascular lymphomatos
Invasion
Invasive ductal carcinoma
invasiveness
Ionizing irradiation
IORT
Iran
Irinotecan
iris metastasis
iron oxide nanoparticle
isolated splenic metastas
isothiocyanates
Italian cancer burden
Italian cancer control
Italian EPIC population
Italian Sarcoma Group
Italy
jaw
jaws
jejunal intussusception
Job's syndrome
joinpoint analysis
Juvenile granulosa cell t
K-ras
k-ras codon 12 mutation
Kaposi's sarcoma
Kaposi’s sarcoma
keratin
Keratin/genetics
keratoacanthoma
Ki-67
Ki-67 antigen
Ki-ras gene
Ki67
Kidney
kidney transplantation
KIT
kit protein
Korea
Krukenberg tumor
Kyphoplasty
lab-on-chip
labelling
Lacrimal sac
Lactulose-mannitol test
Laminin
lamivudine
Laparoscopic cholecystect
laparoscopic splenectomy
Laparoscopic surgery
laparoscopy
Large breast
laryngeal cancer
laryngeal chondrosarcoma
Laryngeal neoplasm
larynx
Larynx carcinoma
late brain metastases
late complication
Late effects
late effects of cancer tr
late relapse
Late side effects
Late toxicity
latent membrane protein 1
Leading cancer sites
Leiomyosarcoma
leptomeningeal metastases
Leucovorin
Leydig cell tumor
Li-Fraumeni syndrome
life tables
Life-style
Life-style questionnaire
Limited stage
lipid-rich carcinoma
Liposarcoma
Liposomal doxorubicin
Liposomes
Liquid-based cytology
literature review
Liver
liver cancer
liver failure
Liver malignancies
Liver metastases
Liver metastasis
liver neoplasm
Liver resection
Liver transplantation
Liver tumors
lobectomy
Lobular carcinoma
lobular carcinoma in situ
lobular neoplasia
Local control
Local recurrence
local tumor recurrence
local-regional recurrence
localized carcinoma of th
localized gastrointestina
localized non-Hodgkin's l
Locally advanced
Locally advanced breast c
Locally advanced breast t
Locally advanced disease
locally advanced lung can
Locoregional chemotherapy
Locoregional radiotherapy
Lomustine
Long-surviving patient
long-term complications
long-term follow-up
Long-term outcome
Long-term remission
Long-term survival
Long-term-survivors
loss of heterozygosity
loss of heterozygosity (L
Loss of heterozygosity,
low dose intensity
low dose rate
lumpectomy
Lung
Lung adenocarcinoma
Lung cancer
lung cancer prognosis
Lung carcinoma
Lung metastases
lung metastasis
Lung neoplasm
Lung neoplasms
lung resection
lung toxicity
lymph node
lymph node diameter
Lymph node excision
Lymph node failure
Lymph node metastases
lymph node sampling
Lymph node status
Lymph node-negative breas
Lymph nodes
Lymphadenectomy
Lymphangioleiomyomatosis
lymphatic mapping
lymphocytes
lymphofollicular infiltra
Lymphoma
Lymphoscintigraphy
MAb CIBCgp185
macrophage
Magnetic resonance
Magnetic resonance imagin
maintenance chemotherapy
major surgery
Male breast cancer
Male breast carcinoma
Malignancy
malignant breast disease
malignant fibrous histioc
Malignant fibrous histioc
malignant giant cell tumo
malignant glioma
malignant gliomas
malignant infiltration of
Malignant melanoma
malignant mesenchymoma
malignant mixed mesoderma
Malignant pericardial tum
malignant peripheral nerv
Malignant pleural Mesothe
malignant thymoma
Malignant transformation
Malnutrition
MALT lymphoma
mammary phyllodes tumor
Mammography
mammography screening
Mandibular metastasis
Mandibular tumors
manifestation
mantle cell lymphoma
Margin involvement
mastalgia
mastectomy
matrix metalloproteinase-
matrix producing carcinom
Mature cystic teratoma
maxillary sinus
MCC
Mediastinal radiotherapy
mediastinal staging
Mediastinum
medical choice
Medical ethics
medical oncologist’s tr
medullary breast cancer
medullary carcinoma
Medullary thyroid cancer
Medullary thyroid cancer
Medullary thyroid cancer
Medullary thyroid carcino
Medullary thyroid carcino
Medullary thyroid carcino
Megestrol acetate
Melanin
melanocytoma
melanoma
Melanoma prevention
Membranous glomerulonephr
MEN 2 syndromes
MEN 2A
MEN 2B
meningeal carcinomatosis
Meningeal hemangiopericyt
Meningioma
Menopause
Menstrual cyles
menstrual induction
mental adaptation to canc
Merkel cell carcinoma
mesenchymal chondrosarcom
mesenchymal tumor
mesenteric cyst
Mesenteric fibromatosis
Mesenteric paraganglioma
Mesenteric thrombosis
mesentery
Mesothelioma
Meta-analysis
metacarpal bone
metachronous metastasis
metaiodobenzylguanidine s
Metaiodobenzylguanidine t
metallic implants
metalloproteinase
metallothioneins
Metanephrines
metaplastic carcinoma
metastasectomy
Metastases
Metastasis
metastasis of unknown ori
metastasis to stomach
Metastatic bone disease
Metastatic breast cancer
Metastatic cancer
metastatic cancers
Metastatic colorectal can
metastatic gastric cancer
metastatic liver disease
metastatic non-small cell
metastatic ovarian tumor
Metastatic prostate carci
Metastatic spinal cord co
metatarsal bones
methodological approaches
methylation
Methylene blue
metronomic therapy
MGMT
mice
microcalcification
Microcalcifications
Microenvironment
micropapillary
Microvascular density
Midline lymphoma
Minimal change disease
minors
Mismatch repair genes
mitogen-activated protein
mitomycin C.
mitomycin-C
Mitoses
mitotic catastrophe
Mitotic index
Mitoxantrone
Mixture models
MLH1
MMP
mobility
molecular diagnostics
Molecular follow-up
Molecular markers
monoclonal antibody
mononuclear cell migratio
Morbidity
morbidity-mortality
Mortality
Moschcowitz's disease
Motility
MRI
MSH2
MTA
MTHFR
mucinous adenocarcinoma
mucinous tumors
Mucosa-associated-lymphoi
mucosal damage
mucosuria
multi-drug resistance
multi-drug resistance pro
multicentric trial
multidisciplinary treatme
multiendocrine failure
multikinase inhibitor
multileaf collimator
Multimodality therapy
multimodality treatment
multiple bladder-prostate
multiple endocrine neopla
Multiple lymphangiomas
multiple malignancies
Multiple malignancy
Multiple myeloma
multiple primary cancers
multiple sclerosis
Multipurpose surveys
Multivariate analysis
Muscle cell proliferation
mutation
myasthenia
mycosis fungoides
myelodysplastic syndrome
myeloid markers
myocardial metastasis
myocardial perfusion defe
myocardial perfusion scin
myoepithelial cells
myoid
Na+-I- symporter
nanomedicine
nanoparticles
nanotechnology
nanomedicine
nanoparticles
nasal septum
Nasopharyngeal cancer
Nasopharyngeal carcinoma
nasopharyngeal neoplasm
Nasopharynx
National survival estimat
Natural killer cells
Neck
neck dissection
neck mass
neck metastases
Neck's tumors
necrosis
negative second-look lapa
neoadjuvant
neoadjuvant chemoradiatio
Neoadjuvant Chemotherapy
neoadjuvant radiotherapy
Neoadjuvant therapy
neoadjuvant,Taxotere
Neoplasm
Neoplasm circulating cell
neoplasm metastasis
Neoplasms
neopterin.
Neovascularization
nephrectomy
Nephrotic syndrome
nephrotoxicity
Nerve-sparing
Network
networks
neural tissue
neurilemmoma
Neuroanatomy
neuroblastoma
neuroendocrine carcinoma
Neuroendocrine differenti
Neuroendocrine tumor
Neuroendocrine tumors
neurofibromatosis 2
neurogliocytoma
Neurological state
Neuron-specific enolase
Neuropathic pain
neurosurgery
neurotoxicity
neutropenia
neutropenic enterocolitis
New bisphosphonates
new schedule
NF-ÛB
NF1
nipple-sparing mastectomy
NIS expression
NIS therapy
Nitric oxide
NK activity
NK cells
NK lymphoma
nm23
Nodal regions
nomograms
Non-functioning adrenocor
non-Hodgkin disease
Non-Hodgkin lymphoma
non-Hodgkin lymphomas
non-Hodgkin’s lymphoma
non-melanoma skin cancers
non-non-Hodgkin's lymphom
Non-palpable breast lesio
Non-palpable thyroid nodu
non-pegylated doxorubicin
Non-platinum chemotherapy
Non-profit clinical trial
non-seminoma
Non-smal cell lung cancer
Non-small cell lung cance
non-small cell type
non-small-cell lung cance
non-viral vectors
Nongestational choriocarc
nonlinear resonance inter
nonpigmented ciliary epit
nonseminomatous germ cell
norcholesterol scintigrap
Nosocomial infections
Nottingham prognostic
novel mutations
NSCLC
Nuclear medicine therapy
nucleic acid delivery
nutrient mixture
nutritional status
Obesity
obscure digestive bleedin
Occult blood
Occult primary
occult/obscure gastrointe
occupational exposure
octreoscan
Octreotide
Ocular
ocular adnexal lymphoma
odontogenic tumors
off-label
older population
oligonucleotides
omentum
Omentum.
Oncocytic neoplasm
oncogene
oncogenes
Oncogenomics
Oncology
Opioid consumption
opportunistic screening
optical biopsy of cancer
optical imaging
optical neuritis
Optimized screening
oral cancer
oral cavity
Oral mucositis
oral precancerous conditi
oral UFT (tegafur-uracil)
oral vinorelbine
orbit
Orbital involvement
Orbital metastasis
Orbital surgery
organisation of care
Orgotein
Oropharynx
Orthovoltage therapy
osteo-oncology
Osteoclastic activation
osteonecrosis
osteopetrosis
osteopontin
Osteosarcoma
osteosarcoma of the kidne
osteosarcomatous differen
outcome
outpatient regimen
Ovarian cancer
Ovarian carcinoma
ovarian endometriosis
ovarian malignancy
ovarian psammocarcinoma
ovarian teratoma
Ovarian tumor
Ovary
over-treatment
overall survival
Overdose
Overexpression
Oxaliplatin
oxidative phosphorylation
p105
p14
p16
p185HER2
p27Kip1
p53
p53 antibodies
p53 gene
p53 mutation
p53 protein
p57Kip2
p63
p73
Pacemaker
Paclitaxel
Paclitaxel-carboplatin
Paget’s disease
PAI-1
Pain mechanisms
painful lipomas
palliative care
palliative care in oncolo
Palliative chemotherapy
palliative radiation ther
palmar-plantar erythrodys
palonosetron
pancreas
Pancreatic cancer
pancreatic carcinoma.
pancreatic cyst
pancreatic ductal adenoca
pancreatic heterotopy of
pancreatic intraductal pa
Pancreatic metastases
pancreatic neoplasm
pancreatic neoplasms
Pancreatic resection
pancreaticoduodenectomy
panitumumab
Pap smear history
Pap smear screening
Pap smears
Papillary carcinoma
Papillary fibroelastoma
papillary thyroid carcino
Paraganglioma
paralytic ileus
parametric model
paranasal sinuses
Paraneoplastic nephrotic
Paraneoplastic neurologic
Paraneoplastic syndrome
Paraplegia
Paraspinal tumors
Parathyroid
parathyroid adenoma
Parathyroid carcinoma
Parathyroid hormone (PTH)
Parathyroidectomy
Parenteral nutrition
parotid carcinoma
parotid gland
parotid neoplasm
partial laryngectomy
pathology
Pathology related markers
Pathway
patient satisfaction
patient-physician relatio
patterns of care
Patterns of failure
paxillin
PCR
PDGF
PEComa
pediatric
pediatric oncology
pediatric tumors
pegfilgrastim
Pegylation
Pelvic CT
Penile metastases
perfusion
Periampullary stromal tum
perineal prostatectomy
Perioperative radiotherap
Peripheral blood progenit
peripheral blood stem cel
peripheral leukocytes
peritoneal carcinomatosis
Peritoneal mesothelioma
Peritonealcancer
Peritonectomy
Peritoneovenous shunt
Peritoneum
peritumoral hepatic tissu
perivascular epithelioid
Permanent prostate Brachy
PET
PET sensitivity
PET.
PET/CT
Pharmaceutical industries
pharmacoeconomics
Pharmacoeconomy
pharmacogenetics
Pharyngolaryngeal squamou
Phase I
Phase II study
Pheochromocytoma
Pheochromocytoma treatmen
Phosphoinositide 3-kinase
photo excitation
Photofrin
Photosensitizer
phyllodes tumor
Physical activity
Physicians
physiotherapy
Pituitary adenoma
pituitary gland
pituitary gland metastasi
placental site trophoblas
planning study
Plasma fatty acid
plasmacytoid
Plasmacytoma
Plastic ring
Plastic surgery
Platinum
pleomorphic adenoma
Pleura
Pleural neoplasms
pleural small cell carcin
Pleurocentesis
Ploidy
Pneumonectomy
point mutations
point-of-care
Pollution
poly(butyl cyanoacrylate)
poly(lactide-co-glycolic
Polyamines
polychemotherapy
polycystic liver disease
Polymerase chain reaction
polymorphism
polymorphous
polysomy
ponicidin
population surveillance
Population survey
Population surveys
population-based
Population-based study
population-based survey
Porphyrins
port site recurrence
Positron emission tomogra
positron-emission tomogra
Post-irradiation sarcoma
Post-radiation osteosarco
Post-remission treatment
Post-traumatic glioma
Post-traumatic meningioma
Post-treatment CIN
Postoperative chemoradiat
postoperative radiochemot
Postoperative radiotherap
Postoperative therapy
PP1 inhibitor
PR
Practice guidelines
pRb
pre-operative chemotherap
Predictive value
Prednisone
Pregnancy
Preoperative chemoradiati
preoperative diagnosis
preoperative immunotherap
preoperative radiochemoth
Preoperative radiotherapy
pretreatment tumor lysis
Prevalence
prevalence of use of comp
prevention
Prevention and control
Priapism
Primary
primary adenocarcinoma
primary bilateral adrenal
primary central nervous s
primary chemotherapy
primary cultures
primary duodenal adenocar
primary hepatic leiomyosa
primary hyperparathyroidi
primary lung tumors
primary osteosarcoma
primary pancreatic lympho
primary systemic therapy
Primitive neuroectodermal
proctocolectomy
progesterone receptor
Prognosis
Prognostic factor
Prognostic factors
Prognostic markers
prognostic parameter
Prognostic score
proliferating trichilemma
Proliferation
proliferation index
prone position
Prophylactic total thyroi
Prospective cohort study
Prospective longitudinal
Prospective study
prostaglandin-endoperoxid
Prostate
Prostate adenocarcinoma
prostate biopsy
Prostate cancer
Prostate carcinoma
prostate neoplasms
Prostate specific antigen
prostate-specific antigen
Prostatectomy
Prostatic ducts
Prostatic neoplasm
prostatic neoplasms
protection
Protein microarray
Protein S
Proteomics
Proteomics technologies
Proton beams
proton therapy
PSA test
Pseudomyxoma peritonei
Psoriasis
psychosexuality
psychosocial
Psychosocial adjustment
psychosocial support
PTCA
PTEN
Pulmonary
Pulmonary adenocarcinoma
Pulmonary blastoma
Pulmonary fibrosis
Pulmonary lymphoma
pulmonary non-Hodgkin’s
Pulmonary valve
Pylethrombosis
pyogenic liver abscess
Pyrene
quality assurance
quality indicators.
quality of care
Quality of life
quality score system
Quantification
quantitative real time po
questionnaire
questionnaires
Radiation
Radiation safety
Radiation therapy
Radiation-induced meningi
Radiation-induced tumors
Radiation-induced
Radical hysterectomy
Radical nephrectomy
radical surgery
radiochemotherapy
Radiofrequency ablation
Radiograph
Radioguided surgery
Radioiodine therapy
radiologic diagnosis
radiologically dense brea
radiometabolic therapy
Radionecrosis
Radionuclide therapy
radioprotection
radiosensitivity
Radiosensitizer
radiosensitizing
Radiosurgery
Radiotherapy
Radiotherapy fractionatio
radiotherapy treatment
Radiotherapy treatment pl
radiochemotherapy
Raloxifene
Ralstonia pickettii
Raltitrexed
ramosetron
Random sample
randomized controlled cli
Randomized controlled stu
Randomized controlled tri
randomized phase III tria
RARb
rare entity
rash
RASSF1A tumor suppressor
RCC
Re-irradiation
reactive lymphoid hyperpl
reactive oxygen species
Recall colitis
receptor
receptors
recognization
recombinant human growth
Recombinant human thyrotr
record-and-verify systems
Rectal adenocarcinoma
Rectal cancer
rectal fistula
rectal injury
Rectal lymphomas
rectal neoplasms
Rectovaginal fistula
Rectovaginal septum
Rectum
rectus abdominis muscle
Recurrence
Recurrent
Recurrent carcinoma
Recurrent high-grade glio
recurrent ovarian cancer
Recurrent rectal carcinom
Reflux esophagitis
Regional chemotherapy
regional medical programs
Regional program
registries
regression
regression analysis
reirradiation
Relapse
relative survival
relative value
Renal cancer
Renal carcinoma
Renal cell cancer
Renal cell carcinoma
Renal failure
Renal metastasis
renal osteosarcoma
renal papillary carcinoma
Renomedullary interstitia
Reproductive factors
Resection
residual lesion
Resistant
resources
respiratory failure
RET oncoproteins
Ret tyrosine kinase
RET/PTC
Retinal metastases
retro-orbital granulocyti
Retroperitoneal liposarco
retroperitoneal mass
retroperitoneal tumor
retrorectal hamartoma
retrorectal tumors
retrospective study
review
rewards
rhabdomyosarcoma
Rheumatoid arthritis
rhuCD40L,TRAF
ring and tandem
risk factor
risk factors
Risk of cancer
RNA
RNA interference
Runx2
S-100 protein
s-phase fraction
S-phase fraction.
sacroplasty
Salivary gland
Salvage radiotherapy
salvage therapy
Sampling bias
Sarcoma
sarcomatoid renal cell ca
Sarcomatosis
Scalene lymph node
scalp
scalp cooling
Schwann cell
Schwannoma
SCID mice
Sclerosing hemangioma
Scoring
Screening
seasonality
Second line
Second malignancies
second primary cancer
second primary tumors
second-hand smoke
second-line
Second-line chemotherapy
secondary breast angiosar
secondary hemicolectomy
Secondary malignancies
secondary prevention
Secondary sarcomas
SEER program
Segmental duodenal resect
selection criteria
Selective estrogen recept
selective internal radiat
self-expanding stent
self-report assessment
seminal vesicle invasion
seminoma
Sensitivity
sentinel lymph node
Sentinel lymph node biops
Sentinel lymph node mappi
Sentinel node
Sentinel node mapping
sequence
sequence variant
sequence-specific primer
sequential chemotherapy
serum
Serum lactate dehydrogena
sestamibi
setup uncertainty
sex cord stromal tumor
Sex-specific rates
sexual dysfunction
SF-36 questionnaire
shoe worker
shoulder movement
shoulder syndrome
Signs
Silver staining
simple cholecystectomy
simultaneous care
simultaneous thyroid carc
Single agent
single nucleotide polymor
single nucleotide polymor
single strand conformatio
single-strand conformatio
single-strand conformatio
sinonasal cancer
siRNA
Sister Joseph's nodule
size
skeletal muscle
skin
skin cancer
Skin metastases
Skin neoplasms
skin squamous cell carcin
skin toxicity
Smac/DIABLO
Small bowel
Small cell carcinoma
Small cell lung cancer
Small cell lung carcinoma
Small intestine adenocarc
Small melanocytic skin le
Small melanoma
Small-cell lung cancer
Smoking
smoking ban
Smoking cessation
Smoking habits
social class
Socio-economic data valid
Sodium iodide
soft tissue sarcoma
Soft tissue sarcomas
soft tissue tumor
soft-tissue tumor
solid pseudopapillary neo
solid tumor
solitary fibrous tumor
Solitary plasmacytoma
somatostatin analogs
Somatostatin analogues
Somatostatin receptor sci
Somatostatin receptors
sorafenib
Sox9
Spain
Specificity
Sphincter saving procedur
sphincter-saving procedur
sphincter-saving surgery
spinal accessory nerve
spinal cord
spindle cell
spindle-cell carcinoma
spleen.
Splenectomy
splenic lymphangioma
splenic metastases
Splenic rupture
Splenomegaly
splenopancreasectomy
Spontaneous internal jugu
Squamous cell carcinoma
squamous cell carcinoma a
squamous cell carcinoma o
Squamous cell carcinoma,V
Squamous cell laryngeal c
stage
stage III
Staging
Standard incidence ratio
statistical method.
Statistical model
Stealth liposomes
stem cell transplantation
stenosis
Stereotactic
stereotactic body radiati
stereotactic radiosurgery
Sternberg tumor
Sternum
Steroid receptors
Steroids
Stevens-Johnson syndrome
Stomach
stomach cancer
stool test
stop-flow
Subcutaneous mastectomy
subdural hematoma
Subdural osteomas
Subgroup analysis
Sugar industry
Suicide
Suicide thoughts
sulfur compounds
Sunburn
sunitinib
Superficial therapy
Superior hypogastric plex
superior mediastinal synd
superior vena cava syndro
supernumerary breast
Superoxide dismutase
supraclavicular adenopath
supraclavicular lymphaden
supraclavicular radiother
supraventricular tachycar
Surgery
surgical complications
Surgical margins
surgical mortality
surgical oncology
surgical procedures
Surgical resection
surgical strategy
surgical treatment
Suriname
Survey
Survival
Survival analysis
SV40
Swiss albino mice
Sympathetic cervical chai
Sympathetic chain
Symporter (NIS)
Symptom management
symptom-to-treatment inte
Symptoms
Synaptophysin
synchronous cancer
Synchronous multicentric
Synchronous presentation
synchronous triple cancer
Synchronous tumors
synergistic effect
synovial sarcoma
systemic chemotherapy
T2 signal intensity
Tamoxifen
Tangential irradiation
tanshinone II-A
target coverage
Target delineation
target therapies
target therapy
Target volume
targeted contrast materia
targeted drug delivery
targeting
taxane
Taxol
Taxotere
TCF regimen
tcr-gamma
Technetium-99m
technique investigation
tectal glioma
telemedicine
Telomerase activity
telomerase RNA
Temozolomide
temozolomide refractory
teratoma
terebrant ulcer
terminal cancer patients
terminal patient
terminally ill
test
testicular cancer
Testicular seminoma
Testicular tumors
Testis
Testosterone,Wistar rats
tetrandrine
thalidomide
Therapeutic guidelines
therapeutic strategies
therapy
therapy-related leukemia
thiamine
Thiols
third-line chemotherapy
Three-dimensional conform
three-dimensional conform
Thrombocytopenia
thrombophilic screening
Thrombosis
Thrombotic thrombocytopen
Thymic carcinoid
thymolipoma
Thymoma
thymus
Thyroglobulin
Thyroglobulin (Tg)
Thyroglossal duct cyst
Thyroglossal duct remnant
Thyroid
Thyroid cancer
Thyroid cancer scintigrap
Thyroid carcinoma
thyroid gland
thyroid lesions
thyroid metastases
thyroid metastasis
Thyroid neoplasms
thyroid nodule
thyroid squamous cell car
thyroid surgery
thyroid tumor
thyroidectomy
time trends
Time-intensity dynamic pr
TIMP3
Tissue remodelling
tobacco
Tobacco smoking
tomotherapy
Tongue
tongue cancer
tonsil
tonsil metastasis
topoisomerase IIa
total colectomy
Total dermatoscopic score
total gastrectomy
total parental nutrition
Toxicity
TP53
TPS commissioning
TRAIL
training
tram
transanal excision
Transarterial chemoemboli
transcatheter arterial ch
Transitional cell carcino
translational research
Transplant-related compli
Transrectal ultrasonograp
transverse colon
trastuzumab
Treatment
Treatment guidelines
treatment monitoring
treatment response predic
treatment verification
Trends
trends in smoking
TRIMprobTM
Triphenylethylenes
triplet
triplet regimen
Trisomy 21
TSPAN1
TTF-1
Tuberculosis
Tumor
tumor and nontumor lesion
tumor bank
tumor burden
tumor cells
Tumor lysis syndrome
Tumor marker
Tumor marker CA 15-3
Tumor markers
tumor metastasis
tumor response
tumor sample
tumor seeding
tumor size
tumor stage
Tumor staging
Tumor-associated mononucl
Tumor-like lesion
tumor-like multiple scler
Tumorigenesis
Tumorlets
Tumors macrophages
Turkish breast cancer sur
tuscany
twins
type-1 neurofibromatosis
Tyrosine kinase
tyrosine kinase inhibitor
ultrasonography
Ultrasound
Ultrasound-guided fine-ne
Umbilical nodule
unconventional cancer tre
undertreatment
undifferentiated esophage
undifferentiated nasophar
uniscale assessment
unknown primary
unknown primary site
unknown primary tumors
unresectable
Unusual metastatic sites
uPA,TIMP
upper aerodigestive cance
Upregulation
Urachal carcinoma
Urbanization
urethane
Urinary bladder metastase
urinary tract
urokinase plasminogen act
urothelial cancer
Urothelial carcinoma
Urothelial carcinoma of t
urothelium.
usage of cam
uterine cervical cancer
uterine cervix cancer
uterine cervix carcinoma
uterine metastasis
Uterine neoplasms
Uterine sarcoma
uterine serous cancer
Uterus
Uveal melanoma
UW-QOL
Vaccination
Vacuum-assisted core biop
Vaginal cancer
validation
validity
Vascular endothelial grow
vascular proliferation
Vascular tumor
vascular tumors
VE-cadherin,VEGF
vectorization
Venous thromboembolic com
Vertebral compression fra
Vertebral tumor
vertebroplasty
videoconference
Vinblastine
Vinorelbine
virtual bio repository
vitamin A
Vitamin D analogs
VM26
vocal fold paralysis
vocal folds
voice disorder
VP3
Weekly administration
Weekly docetaxel
weekly docetaxel and gemc
Weekly paclitaxel therapy
Weekly therapy
Wernicke's encephalopath
WHO histopathological cla
whole abdominal irradiati
whole brain radiotherapy
wnt signaling
Wnt-5a
women
Woringer-Kolopp disease
X-ray computed tomography
X-rays
Xenograft
yolk sac tumor
young
youth smoking
yttrium-90
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