Stage 4 Lung Cancer With Brain Metastases Prognosis

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QUESTION About Stage 4 Lung Cancer With Brain Metastases Prognosis: I’m from Seville. My older brother (57 years old) was operated in December 2006 for lung cancer. He has received chemotherapy and radiotherapy sessions.

On August 1, after visiting the surgeon who operated on him and, even that morning, his oncologist (he had had vision problems in his left eye for several days), he suffered a fading, accompanied by arrhythmia and tension reduction.

Being in the waiting room for emergencies, he suffered a seizure and was two days very serious, in fact, the doctors did not give us much hope. Immediately they did a brain CT scan and discovered at least two metastases.

He was in the hospital admitted for 13 days, suffering severe episodes of hallucinations. With the medication they have controlled something and now they are giving 10 sessions of radiotherapy.

Is there any chance that these sessions are fruitful? What life forecast can we expect? Will it suffer?

ANSWER: Regarding brain metastases, it is necessary to distinguish the short-term danger from the medium-long-term prognosis.

Brain metastases are a serious complication that puts the patient’s life in serious danger. It goes without saying that the brain is a vital organ. As soon as they grow a little, they inflame the surrounding nervous tissues, leading to an accumulation of fluid or cerebral edema.

If that happened in the gut, we would see how the belly swelled. But the skull is bone, it can not be dilated and what happens is that the pressure increases enormously inside the brain, altering many of its functions. This is known as intracranial hypertension and is the cause of epileptic seizures, loss of consciousness and many other disorders.

The use of corticosteroids and radiotherapy solves most cases of intracranial hypertension. Some patients may die in the acute phase of brain metastases, but this is quite rare. The common thing is that the symptoms begin to improve during the first week and have disappeared completely in the approximate term of a month, so that the patient recovers his previous state. Sometimes, this improvement is so fast that it almost seems like a miracle. On the other hand, if after the first or two weeks of radiation no progress is observed, the prognosis is frankly bad.

But, the worst of metastasis in the brain is not its own danger, but what they mean. They are the sure sign that the cancer cells have circulated, and much, through the blood.

It is very common that those who have ramifications in the brain also have other foci hidden in different parts of the body, which do not take long to emerge. As in any medical situation, there are exceptions. There may be lung cancer patients who survive many years after radiation therapy for metastases in the brain, there are even cures. However, the most frequent thing is that things precipitate from that point and life does not last more than about six months.

Ricardo Cubedo
Specialist in Oncology at the Puerta de Hierro University Clinic in Madrid. www.elmundo.es

Stage-4-Lung-Cancer-With-Brain-Metastases-Prognosis-1 Stage 4 Lung Cancer With Brain Metastases Prognosis

 

PROTOCOL

CEREBRAL METASTASES

  • Dr. EMILI COMES MAYMO. Neurology Service
  • Dr. Mª ÁNGELES RAMIS ANDRÉS. Family Medicine Service
  • Dr. MARGARITA CENTELLES RUIZ. Oncology Service
  • Dr. ELISENDA GRIVÉ ISERN. Radiodiagnosis Service

MARCH 2010

INTRODUCTION:

Neurological complications of disseminated or advanced cancer are classified in non-metastatic and metastatic.

Non-metastatic diseases include HCV, infections, metabolic disorders, complications of treatment and paraneoplastic syndromes.

Within the metastatic, there are brain metastases, leptomeningeal, medullary, and compressions and infiltrations of plexuses and pairs cranial.

Both groups require a diagnosis and early treatment given their potential severity and its repercussions in the life of the patient.

Brain metastases represent the most frequent complication and the tumor intracranial most common in adults. Several studies show that they appear in a 10-40% in advanced stages.

It is true that its incidence is increasing due to new techniques of imaging, early diagnosis and the most effective treatments for systemic cancer that prolong the life of the cancer patient. The risk of developing metastasis. Cerebral function varies according to the primary tumor. There are studies that suggest that some chemotherapeutic agents used in the treatment of systemic cancer can produce transient defects in the normal blood-brain barrier, which could favor the development of such tumors in the CNS.

The tumors most frequently associated with brain metastasis are the lung cancer, especially small cell cancer, breast cancer and melanoma.

Meningeal metastases (dural or leptomeningeal) occur in 5-8% of the solid tumors, generally associated with brain metastasis, the frequency of which is 10% in hematologic tumors, especially in high-grade non-Hodgkin lymphomas and in the acute lymphocytic leukemia and in these cases occurring many times isolated without associated brain complications. In breast cancer, dural metastases are almost as frequent as parenchymal, is the neoplasm that with greater Frequently presents them.

On the other hand, spinal metastases occur in 5-10% of neoplasms systemic, being the most frequently associated breast, lung and prostate.

The prognosis is poor and rarely, once the metastases are diagnosed, the Survival is greater than one year of life although, thanks to developments in the diagnosis and treatment, survival is increasing, and it is in many cases the primary tumor, and not the metastatic complication, the cause of death.

Definitions:

Brain metastases: Tumors that develop in the brain, but that they come from a tissue or organ located outside of it.

Meningeal carcinomatosis or Carcinomatous Meningitis: Infiltration of the leptomeninges (pía and arachnoid) or dura mater (paquimeninge) for cancer.

Primary CNS tumors: Those that originate in the brain and marrow spinal, not giving metastasis in general but if leptomeningeal disseminations through of CSF such as medulloblastoma and ependymoma.

Demographics:

  • Age between 50 – 70 years, more frequently in the sixties.
  • Male sex 1.6 / 1. With differences between cancer types according to sex.
  • 5 – 8: 1 Metastasis: Primary CNS tumors.

FORMS OF PRESENTATION OF CEREBRAL METASTASES:

Symptomatic:

I) Initial symptoms: Acute – Subacute (in general).

II) During evolution:

  • Global: Derived from intracranial hypertension:
    • Headache 24-53%, if it appears as a neurological symptom isolated It is likely that brain metastases are multiple.
    • Nausea and vomiting.
    • Cognitive alterations 24 – 35%.
    • Ataxia.
    • Papiledema 10%.
      • Altered level of consciousness: from decrease to coma.

Focal:

  • Crisis comiciales 15 – 54%
  • Hemiparesis 43%
  • Language disorders – Aphasia.
  • Alteration of the visual field.
  • Meningeal irritation

Asymptomatic: Finding in a neuroimaging study.

Temporal relationship with cancer:

– Without known previous cancer (10 – 30%): Lung.

– Initial synchronous diagnosis (30%).

– With cancer already diagnosed:

Active: More frequently pulmonary.

Controlled or in remission, even 20 years: Breast and melanoma.

Frequency of metastasis in different types of cancer:

15 – 40% of patients with cancer will present them.

– 35% of lung cancers:

A) Small cell carcinoma: It represents 15-20% of the total.

80% of metastases appear during the evolutionary course, valuing themselves the possibility of prophylactic cranial radiotherapy in patients with disease limited in complete remission and in those disseminated in treatment, without cerebral involvement, which respond to chemotherapy.

It has been observed in different studies that with this protocol achieved an increase in survival at 3 years of 5.4%, a decrease of 25.3% in the appearance of metastasis and a reduction of annual mortality by 16%, without confirmation of the neurological sequelae delays (dementia-confusion and memory loss) in prospective studies, although 30% had toxicity, mostly headache.

Whenever complete remission is reached after treatment, it will be Prophylactic cranial radiotherapy.

B) Non-small cell carcinoma, especially adenocarcinoma

– 10% of breast cancers:

  • Great evolutionary variability.
  • 10% disease disseminated at the time of diagnosis.
  • 20 – 30% systemic relapse.
  • Few healing possibilities if disseminated.

They can be cerebral, dural meningeal carcinomatosis in 2-5% of patients with disseminated breast cancer, at the bone level with compression medullary or at the level of the SNP with involvement of the brachial plexus. Uncommon association of brain and bone metastases.

The possibility of presenting metastases will depend on:

  • Axillary lymph node involvement.
  • Tumor size (lower risk if it is <2cm).
  • Histological grade (low grade I, intermediate II, high grade III).
  • Presence of tumor emboli (greater if emboli in more than three glasses).
  • Hormonal receptors if they are negative there is a greater risk of metastasis. If they are positive, they are predictive of the response to treatment with hormone therapy.
  • Amplification of the HER2 gene, is associated with greater risk but with greater possibilities of response to trastuzumab.

– 30 – 40% melanomas.

– 8% hypernephroma that represents 80-85% of renal cancers (especially aggressive the subgroup of tumor of the collecting tubules of Bellini).

– 10% Testicular germ cell tumors.

  • Rare isolated.
  • In general, associated with systemic metastasis.

– 5% colon cancers.

– 5% anaplastic thyroid carcinoma. Less frequent in carcinomas papillary, follicular and medullary.

SUSPECTED LOCALIZATION OF PRIMARY CANCER WHEN THE CEREBRAL METASTASES ARE THE FIRST MANIFESTATION OF THE DISEASE:

According to:

  • Frequency.
  • Location.
  • Temporal relationship
  • Number of metastases.
  • Association with bleeding.

Frequency of the different cancers in brain metastases:

1. Route of hematogenous dissemination:

  • Lung 40-50% (2/3 of non-small cells).
  • Mama 15-20%
  • Melanoma 5-10%
  • Renal 5-10%
  • Digestive 5-10%
  • Ovary 3%
  • Prostate 1%
  • Germinales (in young patients).
  • Thyroid.
  • Non-Hodgkin lymphoma (more frequent leptomeningeal).
  • Leukemia. (most frequent leptomeningeal)
  • Bony sarcomas (rare).

2. Dissemination by contiguity

  • Meningeal.
  • Nasopharyngeal.
  • Cranial

Location of brain metastases:

  • Supratentoriales 80 – 85% (cortex union – white substance).
    • Posterior pit 15%
      • Cerebellum 10 – 12%:
        • Pelvics
        • Digestive – colon.
      • Skull base:
        • Prostate.
  • Basal ganglia
  • Meninges (Carcinomatous meningitis).
  • Choroid plexus
  • Pituitary gland
  • Pineal.

Temporal relationship with cancer already known:

1. Previous or Precocious:

  • Lung

2. Late:

  • Mama
  • Melanoma.

Número de Metástasis:

1. Aislada 10%, sin lesión conocida en otro oregano.

  • Riñón
  • Mama
  • Colon

2. Únicas or solitarias, 40% with a lesión en cerebro (1-3% de éstas en trronco cerebral), but with otras lesiones sistémicas.

3. Dos lesiones, 20%.

4. Ancestors, 30%

  • Pulmón
  • Melanoma

Asociación con sangrado intratumoral:

  • Melanoma.
  • Coriocarcinoma.
  • Renal.
  • Pulmonary (target no pequeñas).
  • Testículo.

DIAGNOSTIC:

A) METASSTASIS:

TAC contraste: Metastasis of the hemorrhagic rejection of a sarcoma de Ewing. RMN (FLAIR y T2): Metastasis única neo pulmón sin efecto significant measure.

1. Anamnésis y Exploración Física.

2. Cerebral TAC with Contrast: 90% Sensibilidad. Puede no visualizar tumoraciones

3. RMN Cerebral:

  • Mayor sensitizes the TC before diagnosing metastasis parenquimatosas de pequeño tamaño, sobretodo en fosa posterior, y metastasis meníngeas.
  • Diagnostic: No case of metastasis of the aislada y dudas de laposibilidad de que sean múltiples existe la posibilidad, may be impliedchanges in the conductive therapist, but use dual – triple doses of gadolinium which increases the posibilidad of detectar metastasis <0.5 cm, falls también increases the falsos positivos y el riesgo de fibrosis sistémica Nephrogenic.

Confirmative post-TAC (with evidence of lesiones múltiples en un tercio de las aisladas -solitarias vistas por TAC). Cuando el TAC muestra múltiples metastasis no need to realize RM, and detect alguna metastasis other no va to behave change in the way. TAC sin y con contraste: Metastasis of the extremities of the cranberry and pulmon. Clínica de presentación cefalea e inestabilidad

– Postquirúrgica inmediata (máximo 48-72 horas) is interested in valorar el degree de resección tumoral. (As it is not possible, TAC de control)

4. PET with methionine (no with fluorodeoxyglucose FDG). The sensibilidad of the FDG-PET and menor (61%) que la de la RM in the detection of metastasis cerebrales. El PET with methionine can be used for a variety of hay series largas y es muy little available in medium nuestro.

5. Biopsy.

B) PRIMARY TUMOR LOCALIZER:

1. Anamnesis y exploración física.

2. TAC Torax – Abdominal. La Rx Torax salt in seroprotein is 43-60%.

3. Marcadores tumorales en Sangre y LCR:

If you use diagnostic and diagnostic tools, however pocos is específicos y on máxima utilidad es para controlar el curso evolutivo de la enfermedad. Algunos respects ambas funciones.

Los principales marcadores para cada type de tumor son: Marcadores específicos diagnósticos:

  • CANCER DE PRACTICE: PSA, PSA libre
  • Canecer Hepático: Alfafetoprotein (AFP)
  • Cáncer de Testículo: AFP, B-HCG.

Marcadores de evolución:

  • Cancer de pulmon: CEA, CA 125, CA 19.9.
  • Melanoma: S-100
  • Linfoma no Hodgkin: B2M, IL-6, TNF, Sr-IL-2, PCR.
  • Tumores neuroendocrinos: 5 HIA (orina), CRA (serum), NSE, ProGRP.
  • Cancer de Mama: CEA, CA 15.3
  • Cancer Gástrico: CEA, CA 19.9,
  • Cancer Colorectal: CEA, CA 19.9.
  • Cancer de Próstata: PSA, PSA libre.
  • Carcinomas Orofaríngeos: CEA, SCC, CYFRA 21-1,
  • Cancer Epitelial de Ovario: CA 125, CA19.9.
  • Canecer Hepático: Alfafetoprotein (AFP)
  • Cancer de Páncreas: CA 19.9
  • Cancer de Testículo: AFP, B-HCG.

Otros marcadores menos utilizados:

  • Cancer de pulmonón: SCC, NSE, CYFRA 21-1, Pro GPR, CA 15’3, TAG-72.
  • Linfoma no Hodgkin: B2M, IL-6, TNF, Sr-IL-2, PCR.
  • Cancer Gástrico: TAG-72.
  • Carcinomas Orofaríngeos: CYFRA 21-1,

4. PET with fluorodeoxyglucose: The associazione TAC – PET diagnostic el primary tumor in a 57% casos.

5. Estudios específicos:

  • Mamografía y Ecografía ginecológica en mujeres.
  • Ecografía urológica.
  • Sangre oculta en heces.
  • Gammagrafía ósea.
  • Gammagrafía with octreotide or pentreotide (tumors neuroendocrinos).

6. Anale genetics:

The detección de anormalidades cromosómicas o de cambios genéticos puede ser útil (there is an analytical test of 495 genes in the genesis of 50 genes in 50 tumors a número muy elevado de casos).

  • Cambios chromosomic en linfomas: t (8; 14) (q24; 32).
  • Translocación t (11:22) en tumores neuroepiteliales periféricos y síndrome de Ewing.
  • 12 chromosome 12 l2i (12p) chromosome short excision chromosome en tumors germinales testiculares.
  • Translocación t (3; 13) en el rbdomiosarcoma.
  • Deleción 3p in the carcinoma pulmonar de células pequeñas.

C) CONFIRMATIVE DE ACTIVIDAD DE CÁNCER YA DIAGNOSTICADO:

1. PET with fluorodeoxyglucose.

METASTASIS MENINGEAS
Definition: Invasion de las meninges (leptomeninges o duramadre) en general por
via hematogen, however puede ser contiguidad: de forma directa desde el
parenchymal cerebral cortex, pectoral cortex or prolongation of metastasis
vertebrales, pares craneales or nervios perifericos. El origen mas frecuente de las
metastasis durales via hematogen es: mum> lymphoma> prostata> neuroblastoma. El
origen mas frecuente de las metastasis leptomeningeas es: pulmon, estomago, mama,
ovarian, melanoma, leukemia, lymphoma and tambien and freqente the extension directa de
tumors primarios of SNC.
1. AISLADAS ASOCIADAS TO NEOPLASIA HEMATOLOGICA:
A) Leucemias Agudas:
Infantile lymphocytic: Posibilidad de recaidas with afectacion de SNC
despues of hematologic remission or 50% is not achieved if prophylactic treatment
with irradiation craneal y metrotrexate intravenous, disinfecting at 5% if it realizes
dicha profilaxis.
Adult Lymphocytic: Afectacion menor to 10% of SNC. Let’s handle it
prophylactic requires an increase in neurological recoid interval, sin mejorar el
hematological predicament neither supervisorship.
No Adult Infantile Lymphocytic: A 5-10% desarrollaran one
meningeal complication. No aconseja tratamiento profilactico.
B) Linfomas:
Lymphoblastic Lymphoma 18%.
High grade lymphoma 12%
Linfomas de celulas grandes diffusas 9%
Linfomas no Hodgkin de bajo little freqent grade.
Lymphoma de Hodgkin little freqent.
2. ASOCIADAS A METASTASIS CEREBRALES:
A) Tumores solidos.
Mama
Pulmon, especially celula pequena.
Melanoma.
Genitourinarios.
Digestive tract adenocarcinoma.
Cabeza y cuello (but extension directa).
Adenocarcinoma de primario desconocido.
FORMAS DE PRESENTACION CLINIC:
Sintomas de afectacion de estado general en paciente with cancer:
Nauseas persistentes asociadas o no a vomitos.
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Sintomas de afectacion neurologica multifocal:
Cefaleas.
Afectacion de conciencia.
Afectacion de pares craneales.
Local or radicular pain (especially lumbago).
Motor deficiency or sensory deployment radicular.
Control of Exfinteres Alteration (freq. Menu).
Signs of neurological compromise:
Disinfection asymmetric de reflejos.
Combination of pyramidal syndrome with reflejos exaltados y signo
de Babinsky (cerebral or medular affective) and radiculopathy with
disminucion or perdida de otros reflejos.
DIAGNOSTIC DE METASTASIS LEPTOMENINGEAS:
1. RMN: The captacion de contraste de las meninges no es especifica y puede
corresponder to:
-Meningitis viral. bacterial, quetical or granulomatous.
– Arthritis rheumatoid and otros procesos inflammatorios.
-hypopic pituitary hypertension.
-Periodos postneuroquirurgicos inmediatos.
-Hipotension intracraneal trans PL repetidas.
– Subarachnoid hemorrhage.
-hematopoyesis extramedular
pial hypervascularization (cortical infarction, angiomatosis leptomeningea,
angiitis granulomatosa, melanosis, neurocutaneous, c)
2. Lumbar puncture:
It transduces the TAC or RMN practitioner to those hypersensitive discs
Endocraneana.
Exist the posibilidad de la necesidad de punciones lumbares
multiples before getting a positive cytoplasm of 87% trans 3
PLs, celebrating the cisternal puncion or including the
biopsy of meningitis.
LCR Characteristics:
1. Inespecificas:
Increased pressure: 40 – 50% de casos.
Pleocitosis.
Proteinas aumentadas: 70% – 75%.
Glucose moderates or intensely baja: 75%.
2. Diagnosticas:
a) Citology para celulas malignas: High 95%
with sensibilidad entre and 70-95% follow the cantidad de muestra
(10 mL) and the rapid processing step.
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b) Marcadores tumorales: Los valores superiores en 2-3 veces
of plasma avalan el compromising meningeal.
– Especificos:
Beta2-microglobulin: Lymphoma.
Alpha-Protein: Hepatic Carcinoma.
Chorionic Gonadotropin beta:
Coriocarcinoma and Embryonic Carcinoma.
Antigen Carcinoma Embrionary CEA-:
Mom, Pulmon. Digestive Tracto y Ovario.
– Inespecificos:
Reflexive alterations in metabolism and cellular neoplasia
en el LCR:
LDH. isoenzymes 3-4-5.
Beta glucuronidase 90% of sensitivity and specificity.
PRONOSTIC DE LAS METASTASIS CEREBRALES:

Existing variables demograficas and clinicas que son indices predictivos de la superviencia en pacientes con metastasis cerebrales. Son variables importantes the edad, el estado general (representado generally
but the escale of Karnofsky), the number of metastases, el
primary tumor type y systemic tumor actividad
(controlado / no controlado).

If you consider that Karnofsky escala la que mejor
predicts the supervisor of the patient.

At the same time, transcurrent enter the tumor diagnostic
primary hasta the aparicion de lesiones cerebrales puede
Predecir and Predictive, Especially En El Cancer
mama y melanoma. Mayor interrupted my bribe, I predicted.
Dada the impor- tance
but estos the indexes and predictions of the patient, if he intentado create a clasificacion
predictable de la mortalidad en presencia de metastasis cerebrales. The mas utilizada,
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surge para los pacientes tratados with holocraneal radiotherapy and if it comfortably como
Clasificacion RPA (Recursive Partitioning Analysis). Divide into individual individually
grupos: Clase I, II, III (Chart page 14). El tiempo estimado de vida es en la clase I
de unos 7.2 meses, en la II de 4.2 meses y en la III de 2.3 meses.
An escalating alternative opens up to the pacientes sometidos at radiocirugia que
recibe el nombre de SIR (Score Index for Radiosurgery). It does not work for parameters
but the clasificacion RPA and the number of metastases and the volume of the lesion
mayor. If it points 0-10.
There will be a new escalator, GPA (Graded Prognostic
Assessment), which only values ​​the parameters: Edad (.60; 50-60; <60), Karnofsky (<70; 70-80; 90-100), number of metastasis cerebrales (> 3; 2-3; 1) y
metastasis extracraneales (presentes; no aplicables; ninguna). Let it fall to one
punctuation of 0, 0.5 or 1. This is the case with demonstrating ser menos subjetiva y mas
cuantitativa que el rest, pero aun debe ser validada.
En general i predostico es pesimo. As far as I’m concerned, the experience of seeing it
reduced to 1-3 meses, with esteroid treatment increases 1-2 meses y with radiotherapy
holocraneal increases otros 6 meses, however en manyos casos empeora la funcion
cognitive.
TRATAMIENTO:
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CLASIFICASICON RPA (Recursive
partitioning analysis)
1. SYMPTOMS:
A) CORTICOIDES:
Disrupted by peripheral edema and intracraneal pressure with the que
mejoran los sintomas como headache, nausea, confusion y debilidad y
favorcen penetracion de otras drogas en el SNC.
If swallowed use Dexamethasone to dosage between 8 and 24 mg / day
despues that the disminuyendo hasta dosis de mantenimiento de unos 4-6 mg / dia.
B) ANTIEPILEPTICOS:
On prophylactic use, no justificado ya que no disminuyen el riesgo de
padecer a primary crisis and ademas tienen multiples interacciones, sobretodo
los clasicos, but on enzymatic induction induction, sobre otros pharmacos, incluidos
los utilizados para quimioterapia.
Hasta no hace mucho se utilizaba phenytoin but ser el uni with diferentes
vias de administracion, includes the intravenous.
If you have a pre-farm pharmacy you can use it but via the intravenous y no
interact with cytochrome level P450 como el leviteracepam or el
valproate, however at the end of the day can increase the myelotoxicidad de la
Chemotherapy.
The gabapentin, tambien util, holds the limitacion de no poder used by the way
IV.
Deben reservarse los AEDs para aquellos pacifices que presenten crisis (el
20% de los pacientes with metastasis cerebrales debutan with an epileptic crisis), para
los que tengan, but on localizacion y tamano, a high riesgo de presentarlas y, en
general, los usan los neurocirujanos en the immediate period (7 dias) postoperative.
C) ANALGESICOS:
Tratamiento del dolore, with el objetivo de mejorar the calidad de vida del
paciente. No correspondence to this presentation is descripcion de los diferentes
pain of the pain.
2. CURATIVE / PALITIVE:
Existing cuatro grandes grupos de tratamientos:
– Cirugia
– Holocraneal Radiotherapy
– Radiocirugia Estereotaxica
– Quimiotherapy
A) CIRCUIT:
Generally, if it pacients with a single metastasis y buen
estado general.
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Sus beneficios mas importantes are the rapid confirmation of the type
but the tumor, the disinfection of the efecto masse of the derivatives
Posible desaparization of the clinic relacionada with the metastasis.
Los ultimos estudios demuestran que en la mayoria de los pacientes
with estos criterios, and the posterior treatment with holocraneal radiotherapy,
greatly enhances the visual experience.
I pacientes with multiples metastasis only if I use the cirrus
while there is a dominant symptomatic and symptomatic lesion.
B) HOLOCRANEAL RADIOTHERAPY:
El regimen mas utilizado es de 35Gy repartidos en fracciones de
2.5Gy during 14days (fractions of diary masses of 3Gy incremental
neurotoxicidad sin mejorar los resultados.). Este trattamento if I use it
ademas de para los pacientes previamente descritos, tambien para
pacientes with multiples metastasis, with pobre estado funcional or with
systemic active or incontrolable tumor no candidatos in cirugia or
radiocirugia.
Indeed, if he is investigating algunas sustancias que,
anaphylaxis in radiotherapy, I would like to supervise, if it is
denominational radiosensitizer and algunas de estas son el motexafin
gandolinio (cancer de pulmon) o efaproxiral (cancer de mama).
However, you can take the dose (75mg / m2) of temozolamide
(quimioterapico) to radiotherapy, which gives buenos resultados with one
toxicidad aceptable to cancer and pulmonary melanoma.
C) ESTEREOTAXIC RADIOCIRUGIA:
Se basa en el empleo de multiples haces convergentes para ofrecer
una unica dosis alta de radiacion local a un volumen de destino discreto
(3-3.5 cm. de diametro maximo).
Los tumores que mas se benefician de esta tecnica son los llamados
gtumores radio-resistentesh como el carcinoma de celulas renales, el
melanoma y el sarcoma. Las lesiones en las que es mas util son aquellas
que tienen un tamano reducido, forma esferica y con distintos margenes
radiograficos y patologicos.
Se puede combinar con radioterapia holocraneal, con buenos
resultados, sobretodo en las metastasis unicas.
Las complicaciones mas frecuentes son la aparicion de edema en las
primeras dos semanas de tratamiento, crisis epilepticas en las primeras
24-48 horas y radio-necrosis a largo plazo.
D) QUIMIOTERAPIA:
Se reserva para pacientes con metastasis generales en los que las
otras alternativas han fracasado.
La respuesta de las metastasis cerebrales a la quimioterapia no tiene
porque ser paralela a la respuesta del tumor o la de las metastasis extracraneales.
En general las tasas de respuesta del tumor primario a la
quimioterapia son del 30-80% en el carcinoma pulmonar de celulas
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pequenas, 30-50% en el cancer de mama, 10-30% en el carcinoma de
pulmon de celulas no pequenas y un 10-15% en el melanoma.
ALGORITMO DE TRATAMIENTO DE LOS PACIENTES CON METATASIS
CEREBRALES:
A) METASTASIS CEREBRALES SOLITARIAS:
1. LESION . 3 cm DE DIAMETRO MAYOR:
– Radio-cirugia con seguimiento RMN cada 2-3meses. — Cirugia
si la lesion es resecable y:
– Diagnostico no establecido.
– Tumor radio-resistente histologicamente
(Melanoma, Sarcoma y Carcinoma de celulas
renales).
– Lesion con efecto masa o lesion de gran tamano
sintomatica.
– Pacientes con buen pronostico sin metastasis
extra-craneales.
– Radioterapia holocraneal con o sin Radiocirugia
coadyuvante, o post cirugia.
2. LESION > 3 cm DE DIAMERO MAYOR:
– Cirugia en pacientes con buen pronostico de la enfermedad de
base, si la lesion es resecable.
– Radioterapia holocraneal con o sin Radiocirigia adyuvante.
B) OLIGOMETASTASIS (2-4 LESIONES CEREBRALES):
– Radioterapia holocraneal con o sin Radio-cirugia (se pueden
considerar como tumores . 3 cms no tributarios a cirugia.).
– Radio-cirugia con vigilancia exhaustiva si la lesiones son pequenas
o radio-resistentes.
C) MULTIPLES METASTASIS (>4 LESIONES CEREBRALES):
– Radioterapia holocraneal
D) METASTASIS CEREBRALES RECURRENTES:
1. Radioterapia Holocraneal si:
– No Radioterapia holocraneal previa.
– Multiples lesiones.
2. Cirugia si:
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– Lesion solitaria o con una lesion dominante.
– Buen pronostico.
– Efecto masa.
– Lesion resecable.
3. Radiocirugia si esta dentro de los parametros de tratamiento y hay
un numero limitado de lesiones.
4. Radioterapia estereotaxica.
5. Quimioterapia:
A) Cancer de mama:
Con combinaciones de agentes que son efectivos en el cancer de
mama como la ciclofosfamida, el 5-FU, el metotrexate, la vincristina, el
cisplatino o el etopoxido.
Altas dosis endovenosas de metotrexate pueden conseguir una buena
respuesta en las metastasis recurrentes, aunque puede causar una gran
neurotoxicidad, lo que limita su uso.
La temozolamida, que es uno de los agentes mas estudiados, parece
no ser demasiado efectiva como unico agente o en combinacion con los
otros, a excepcion del capecitabino, en las metastasis recurrentes.
En las pacientes con HER-2 positivo tratadas con trastuzumab que
controla la enfermedad sistemica pero crea gsantuarios cerebralesh donde
el tumor puede metastatizar se esta observando buen control de las
metastasis cerebrales con los inhibidores del EGFR como lapatinib.
B) Cancer de pulmon:
El carboplatino y cisplatino tienen un efecto moderado en el cancer
de pulmon no microcitico. La temozolamida es efectiva en metastasis
recurrentes, y parece estar demostrando mejores resultados en
combinacion con vinorelbina.
Por otro lado, esta siendo estudiada la accion de los inhibidores del
EGFR (gefitinib y erlotinib) que han alcanzado unas tasas de curacion
altas (en especial en pacientes con la mutacion L858R en el gen del
EGFR, en los que se observan hasta el 75% de remisiones).
Ademas, se esta ensayando con los inhibidores del VEGF
(bevacizumab, sorafenib, sunitinib y enzastaurin) que parecen tener
actividad en canceres avanzados no microciticos.
En el carcinoma de celulas pequenas se sugieren como agentes mas
importantes, la isofosfamida o topotecan.
C) Melanoma:
La fotemusina y la temozolamida son los agentes mejor estudiados
para este tipo de cancer, ambos como agentes unicos o en combinacion
con la radioterapia.
Por otro lado, la temozolamida en combinacion con la talidomida
puede controlar mejor la enfermedad a expensas de una gran toxicidad
(hemorragias intracraneales y femonenos tromboticos).
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