Specialty
Spotlight

 




 


Oncology


 

 





Central
Nervous System Tumors

  

  • Breen
    P, Flickinger JC, Kondziolka D, et al [Univ of
    Pittsburgh, Pa]

    Radiotherapy
    for Nonfunctional Pituitary Adenoma : Analysis of
    Long-term Tumor Control

    J
    Neurosurg 89: 933-938, 1998

           

    This
    study is of 120 patients who received radiation for
    nonfunctional pituitary adenoma.
    Actuarial tumor control rates were 87.5% at 10
    years, 77.6% at 20 years 
    and 64.7% at 30 years.

            

    Tumor
    progression after RT was significantly more common with
    oncocytoma than in those with nononcocytic null cell
    adenoma

            


  • Alba Ariela Brandes, Valentina Palmisano, Lara Maria Pasetto, Umberto Basso, and Silvio Monfardini (Divisione di Oncologia Medica, Azienda Ospedaliera, Via Giustiniani 2, 35100 Padova, Italy)

    High-Dose Chemotherapy with Bone Marrow Rescue for High-Grade Gliomas in Adults 

    Cancer Investigation 2001 Vol. 19 (1) Pg. 41-48

          


    High grade gliomas, anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) represents 25% of all primary brain tumors. Standard treatment include surgical debulking followed by radiotherapy and with or without chemotherapy. 

        


    The most active drugs are nitrosources, BCNU and lomustine (CCNU). High dose BCNU based induction regimens followed by autologous BMT (ABMT) done after surgery of glioma and finally radiotherapy could delay but not prevent tumor progression. 

         


    An important finding is that when radiotherapy administered between chemotherapy, encephalopathy and neurological deterioration was more common.

        


    Other studies when high dose BCNU induction regimens followed by ASCT have been used in a recurrent setting have revealed improved responses but did not modify median survival (MST). High dose BCNU chemotherapy had toxicity, involving the lungs and liver. 

         


    The benefit obtained from ASCT whether it could outweigh the toxicity is not clear.
    .

         

  • Roger Stupp, Marc Gander, Serge Leyvraz and Edward Newlands (Multidisciplinary Oncology Center, University Hospital CHUV, Lausanne, Switzerland, and Department of Cancer Medicine, Charing Cross Hospital, London, UK)

    Current and Future Developments in the Use of
    Temozolomide for the Treatment of Brain Tumours 

    The Lancet Oncology September 2001 Vol. 2 (9) Pg. 552-560

          

    Temozolomide, an alkylating agent is rapidly and completely absorbed after oral administration and spontaneously converts into active metabolite without the need for enzymatic demethylation in the liver.

          

    It has excellent penetration into all body tissues including the brain. The mechanism of resistance of this agent is mediated thus the enzyme O6-alkylguanine transferase (AGT) brain tumours express low concentration of this enzyme.

         

    The excretion of temozolomide (TMZ) is mainly via the kidney with plasma half-life 1.8 hours. The schedule most widely used is daily treatment for 5-days of TMZ at dose of 200
    mg/m2 or 150 mg/m2 for the first cycle in patients who have received chemotherapy previously.

          

    The dose limiting toxic effect is thrombocytopenic. Phase I studies of continuous administration of TMZ is 75
    mg/m2 daily for 6-7 weeks and dose limiting toxicity is myelosuppression whether continuous low dose administration and higher dose intensity have lead to improved efficacy remains unclear.

           

    In brain tumours responses are rare and delayed so progression free survival may better reflect a meaningful clinical benefit than usual response criteria on the basis of phase II studies. TMZ has been approved for the treatment of malignant glioma mainly recurrent glioblastoma, anaplastic astrocytoma. 

           

    The benefit in such patients is in time to progression and possibly survival will be few months at the best and hence efforts are to integrate TMZ in multimodality treatment.

          

    TMZ has been tried as neoadjuvant therapy in patients with high grade gliomas or glioblastomas. Complete response occurred in 40% and partial response in 20% irrespective of histology those who have responded are the ones who might benefit from more intensive treatment i.e. concomitant
    CT+ RT or additional adjuvant chemotherapy.

          

    TMZ and radiation have been tried with some adverse effect such as lymphocytopenia and
    Pneumocystis carinii. TMZ has been tried with other agents such as nitrosoureas, procarbazine and irinotecan.

           

    TMZ has shown activity as second-line therapy in anaplastic oligodendroglioma and oligoastrocytoma. TMZ in low grade gliomas may be used as an alternative to immediate radiotherapy in particular the novel continuous exposure schedules have some theoretical advantage in these slowly proliferating diseases.

           

    TMZ has been tried in other metastatic brain disease with some responses in non small cell lung cancers. Primary CNS lymphoma and stabilization in metastatic
    melanoma.

          

  • Mark R. Gilbert (Department of Clinical Neuro-Oncology, University of Texas, Houston, USA)

    Brain Metastases: Still an ‘Orphan’ Disease?

    Current Oncology Reports Vol. 3(6) November 2001 Pg. 463-466

            

    Brain metastasis are nearly ten times more common than primary brain tumors despite the high incidence relatively few studies have focused on treatment or biological etiology of brain
    metastasis.

           

    A landmark study is neuro-oncology by Curran et al has markedly altered the approach to brain tumor clinical trial. This study evaluated prognostic factor in 1578 patients with malignant gliomas treated in RTOG trials. The study determined six distinctive prognostic groups on the basis of age (<50 vs.
    ³50) histology, KPS, mental status, extent of tumor resection duration of symptoms prior to diagnosis, neurological function, and radiotherapy dose.

            

    A similar approach is developed for clinical trials in evaluating patients with brain metastasis and three distinct prognostic groups on the basis of small numbers of pretreatment variables such as KPS,
    ³70 OR <70, primary cancer controlled, age (<65³) metastasis to brain only and other sites.

           

    The class
    I patients were KPS
    ³70, primary cancer controlled, age <65, metastasis to brain only, KPS <70 were class
    III and the intermediate class
    II were primary cancer uncontrolled age
    ³65 and metastases to brain and other sites.

            

    Several studies have validated varying survival and prognostic groups as per the recursive partitioning analysis classification system mentioned earlier.

          

  • Kondziolka D, Patel A, Lunsford LD, et al (Univ of Pittsburgh, Pa)

    Stereotactic Radiosurgery Plus Whole Brain Radiotherapy Versus Radiotherapy Alone for Patients With Multiple Brain Metastases 

    Int J Radiat Oncol Biol Phys 45: 427-434, 1999

           

    This study of 27 patients with multiple brain metastasis (2-4 in numbers) and 25 mm or less in diameter with known primary tumors were randomly assigned to WBRT alone or with
    radiosurgery.

          

    The local failure rate at 1 year was 100% in patients undergoing WBRT and only 8% in patients undergoing WBRT + radiosurgery and median time to local failure was also much better with combined WBRT + radiosurgery (6 months v/s 36 months).

         

    And tumor control of the disease especially in patients with brain metastases (2-4) was better with combined WBRT and radiosurgery than with WBRT alone.

          

  • Shafron DH, Friedman WA, Buatti JM, et al (Univ of Florida, Gainesville)

    LINAC Radiosurgery for Benign Meningiomas

    Int J Radiat Oncol Biol Phys 43: 321-327, 1999

          

    This study of 70 patients with benign meningiomas of which 32 had failed previous surgery and one had received radiotherapy earlier.

         

    LINAC-based radiosurgery for benign meningiomas provided 100% local control and that was maintained during an average follow-up of 23 months.

          

  • Franciosi V, Cocconi G, Michiara M, et al (Azienda Ospedaliera di Parma, Italy, et al)

    Front-line Chemotherapy With Cisplatin and Etoposide for Patients With Brain Metastases From Breast Carcinoma, Nonsmall Cell Lung Carcinoma, or Malignant Melanoma: A Prospective Study

    Cancer 85: 1599-1605, 1999

          

    A previous study had revealed that the combination of cisplatinum and etoposide are highly active against brain metastases from breast
    carcinoma.

          

    This study of 116 patients treated with front line cisplatinum 100 mg/m2 day 1, and etoposide 100 mg/m2 on days 1, 3 and 5 or on days 4, 6 and 8 every 3 weeks had brain metastasis from breast carcinoma (BC) in 52%, NSCLC in 40% and malignant melanoma (MM) in 8%.

         

    Almost 40% of patients with breast cancer had response and 30% with lung cancer. The median survival rates for patients with BC, NSCLC, and MM were 31 weeks, 32 weeks, and 17 weeks respectively.

           

    The editor comments that these figures would suggest the use of chemotherapy more frequently than earlier in patients with brain metastasis from BC and
    NSCLC.

        

  • Jeffrey S. Weinberg, Frederick F. Lang, and Raymond Sawaya (Department of Neurosurgery, University of Texas, Anderson Cancer Center, Houston, USA)

    Surgical Management of Brain Metastases 

    Current Oncology Reports Vol. 3(6) November 2001 Pg. 476-483

            

    Systemic malignancies with high propensity to involve the brain are lung, breast, kidney, colon, and melanoma with improved therapy for systemic malignancies, the incidence of metastasis brain tumor is increasing.

         

    The indications for surgical intervention in a patient with suspected brain metastasis are tissue diagnosis, relieve tumor mass effect, decrease tumor burden and provide local cure.

          

    Surgical resection of single brain metastasis followed by WBRT is superior to only WBRT. Most of such cases die from progression of systemic disease rather than brain metastasis. The other important factors for surgical resection are functioning status of the patient, Karnofsky performance status (KPS) of 70 or higher, neurological deficit and earlier response to steroids and those with short expectancy (less than 3 months). Other important factors prior to consideration of surgery include the histology of the tumor for example lymphomas, germinoma and small-cell lung carcinoma are radiosensitive and tumor is optimally treated with radiation.

          

    Surgical resection of multiple metastatic lesions if accomplished by resection of all this masses an improved prognosis can be expected. Radiation following surgery depends on the radiosensitivity for example in non-small cell lung cancer those who received WBRT had a definite decrease in rate of metastasis as compared to melanoma and colon.

           

    Stereotactic radiosurgery involved multiple weak, well-collimated beams of ionizing radiation focussed by stereotaxy on the metastatic lesion. Only lesions less than 3 cm can be treated and no histologic verification is possible. In a single brain metastasis radiosurgery was at least as effective as resection and WBRT whereas results are not favorable for radiosurgery if multiple metastasis.

          

    The other approach by some investigators is to include radiosurgery as a part of multimodality therapy for patients with multiple brain metastasis.

                  

  • John C. Flickinger (Departments of Radiation Oncology and Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, USA)

    Radiotherapy and Radiosurgical Management of Brain Metastases

    Current Oncology Reports Vol. 3(6) November 2001 Pg. 484-489

           

    Whole brain radiotherapy (WBRT) has been the standard and definitive therapy for brain metastasis. 50% of the patients show symptomatic improvement. Median survival of such patients is 4-6 months. Acute side effects such as tiredness, hair loss, and skin redness are well known.

          

    The other side effects such as cognitive function deterioration and declining IQ scores in young children have to be considered. In patients with small-cell lung cancer abnormal neuropsychological and mental status test noted. The conventional fractionated WBRT for multiple brain metastasis has a recurrence rate of 100%.

          

    Radiosurgery has emerged an important therapeutic intervention for controlling brain metastasis which are small to moderate size (<4 cm) and has emerged equal or surpass rates with surgery and
    WBRT. 

         

    Those patients with single brain metastasis radiosurgery alone is an effective therapy. In those with multiple brain metastasis one reasonable option is surgery in a single dominant hemorrhagic metastasis and radiosurgery to other unresected brain metastasis before wound healing have progressed enough to start
    WBRT. 

         

    The acute toxicity of radiosurgery are seizures, puffy eyes and delayed neurological toxicity are also of concern.      

                                                                                               

  • Charles A. Conrad (Department of Neuro-Oncology, University of Texas M. D., Anderson Cancer Center, Houston, USA)

    Chemotherapy for Metastatic Tumors to the Central Nervous System   

    Current Oncology Reports Vol. 3(6) November 2001 Pg. 490-494   

                                           

    Metastatic tumor to brain are commonly from primary lung cancer (small-cell and non-small-cell) malignant melanoma, renal cell carcinoma and colorectal cancer.        

                                                

    The perception of poor effectiveness of chemotherapy in metastatic brain disease (MBD) are impaired delivery of chemotherapy due to impenetrability of the blood-brain barrier (BBB), drug resistance of solid tumor clones and the fact that brain metastasis occurs in the setting of drug failure.             

                                           

    Micrometastatic foci do not cause break in BBB however increasing metastatic lesion abrogate the BBB. The current consensus is that although the role of BBB has importance in harboring the microscopic tumor foci.    

                               

    The overall impediment it has on treatment failure is questionable. This is supported by clinical data when response in patients with brain metastasis from chemosensitive tumors such as SCLC or chorio carcinoma are known with combination chemotherapy. Some tumors that have predilection (tropism) for brain metastasis have intrinsic resistance to chemotherapy such as melanoma, renal cell carcinoma. The mechanism of cell survival and other signal transduction mediated pathways involves growth factors, such as VEGF, mutated p53 may play a role.    

                                              

    The other form of resistance to primary chemotherapy and thereby having brain metastases would have a group of cells, which preferably favor growth of drug resistant clones.        

                                                  

    Recently large series have begun to demonstrate positive impact of chemotherapy for patients with selected group of patients with brain metastasis. The role of CDDP followed by vinorelbine and docetaxel in NSCLC patients with brain metastasis and the effect of teniposide in SCLC was not different from lesions in other metastatic sites.           

     


 

 



 

 

Specialty Spotlight

 

 

Central Nervous System Tumors
  

  • Breen P, Flickinger JC, Kondziolka D, et al [Univ of Pittsburgh, Pa]
    Radiotherapy for Nonfunctional Pituitary Adenoma : Analysis of Long-term Tumor Control
    J Neurosurg 89: 933-938, 1998
           
    This study is of 120 patients who received radiation for nonfunctional pituitary adenoma. Actuarial tumor control rates were 87.5% at 10 years, 77.6% at 20 years  and 64.7% at 30 years.
            
    Tumor progression after RT was significantly more common with oncocytoma than in those with nononcocytic null cell adenoma
            

  • Alba Ariela Brandes, Valentina Palmisano, Lara Maria Pasetto, Umberto Basso, and Silvio Monfardini (Divisione di Oncologia Medica, Azienda Ospedaliera, Via Giustiniani 2, 35100 Padova, Italy)
    High-Dose Chemotherapy with Bone Marrow Rescue for High-Grade Gliomas in Adults 
    Cancer Investigation 2001 Vol. 19 (1) Pg. 41-48
          
    High grade gliomas, anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) represents 25% of all primary brain tumors. Standard treatment include surgical debulking followed by radiotherapy and with or without chemotherapy. 
        
    The most active drugs are nitrosources, BCNU and lomustine (CCNU). High dose BCNU based induction regimens followed by autologous BMT (ABMT) done after surgery of glioma and finally radiotherapy could delay but not prevent tumor progression. 
         
    An important finding is that when radiotherapy administered between chemotherapy, encephalopathy and neurological deterioration was more common.
        
    Other studies when high dose BCNU induction regimens followed by ASCT have been used in a recurrent setting have revealed improved responses but did not modify median survival (MST). High dose BCNU chemotherapy had toxicity, involving the lungs and liver. 
         
    The benefit obtained from ASCT whether it could outweigh the toxicity is not clear. .
         

  • Roger Stupp, Marc Gander, Serge Leyvraz and Edward Newlands (Multidisciplinary Oncology Center, University Hospital CHUV, Lausanne, Switzerland, and Department of Cancer Medicine, Charing Cross Hospital, London, UK)
    Current and Future Developments in the Use of Temozolomide for the Treatment of Brain Tumours 
    The Lancet Oncology September 2001 Vol. 2 (9) Pg. 552-560
          
    Temozolomide, an alkylating agent is rapidly and completely absorbed after oral administration and spontaneously converts into active metabolite without the need for enzymatic demethylation in the liver.
          
    It has excellent penetration into all body tissues including the brain. The mechanism of resistance of this agent is mediated thus the enzyme O6-alkylguanine transferase (AGT) brain tumours express low concentration of this enzyme.
         
    The excretion of temozolomide (TMZ) is mainly via the kidney with plasma half-life 1.8 hours. The schedule most widely used is daily treatment for 5-days of TMZ at dose of 200 mg/m2 or 150 mg/m2 for the first cycle in patients who have received chemotherapy previously.
          
    The dose limiting toxic effect is thrombocytopenic. Phase I studies of continuous administration of TMZ is 75 mg/m2 daily for 6-7 weeks and dose limiting toxicity is myelosuppression whether continuous low dose administration and higher dose intensity have lead to improved efficacy remains unclear.
           
    In brain tumours responses are rare and delayed so progression free survival may better reflect a meaningful clinical benefit than usual response criteria on the basis of phase II studies. TMZ has been approved for the treatment of malignant glioma mainly recurrent glioblastoma, anaplastic astrocytoma. 
           
    The benefit in such patients is in time to progression and possibly survival will be few months at the best and hence efforts are to integrate TMZ in multimodality treatment.
          
    TMZ has been tried as neoadjuvant therapy in patients with high grade gliomas or glioblastomas. Complete response occurred in 40% and partial response in 20% irrespective of histology those who have responded are the ones who might benefit from more intensive treatment i.e. concomitant CT+ RT or additional adjuvant chemotherapy.
          
    TMZ and radiation have been tried with some adverse effect such as lymphocytopenia and Pneumocystis carinii. TMZ has been tried with other agents such as nitrosoureas, procarbazine and irinotecan.
           
    TMZ has shown activity as second-line therapy in anaplastic oligodendroglioma and oligoastrocytoma. TMZ in low grade gliomas may be used as an alternative to immediate radiotherapy in particular the novel continuous exposure schedules have some theoretical advantage in these slowly proliferating diseases.
           
    TMZ has been tried in other metastatic brain disease with some responses in non small cell lung cancers. Primary CNS lymphoma and stabilization in metastatic melanoma.
          

  • Mark R. Gilbert (Department of Clinical Neuro-Oncology, University of Texas, Houston, USA)
    Brain Metastases: Still an ‘Orphan’ Disease?
    Current Oncology Reports Vol. 3(6) November 2001 Pg. 463-466
            
    Brain metastasis are nearly ten times more common than primary brain tumors despite the high incidence relatively few studies have focused on treatment or biological etiology of brain metastasis.
           
    A landmark study is neuro-oncology by Curran et al has markedly altered the approach to brain tumor clinical trial. This study evaluated prognostic factor in 1578 patients with malignant gliomas treated in RTOG trials. The study determined six distinctive prognostic groups on the basis of age (<50 vs.
    ³50) histology, KPS, mental status, extent of tumor resection duration of symptoms prior to diagnosis, neurological function, and radiotherapy dose.
            
    A similar approach is developed for clinical trials in evaluating patients with brain metastasis and three distinct prognostic groups on the basis of small numbers of pretreatment variables such as KPS,
    ³70 OR <70, primary cancer controlled, age (<65³) metastasis to brain only and other sites.
           
    The class
    I patients were KPS ³70, primary cancer controlled, age <65, metastasis to brain only, KPS <70 were class III and the intermediate class II were primary cancer uncontrolled age ³65 and metastases to brain and other sites.
            
    Several studies have validated varying survival and prognostic groups as per the recursive partitioning analysis classification system mentioned earlier.
          

  • Kondziolka D, Patel A, Lunsford LD, et al (Univ of Pittsburgh, Pa)
    Stereotactic Radiosurgery Plus Whole Brain Radiotherapy Versus Radiotherapy Alone for Patients With Multiple Brain Metastases 
    Int J Radiat Oncol Biol Phys 45: 427-434, 1999
           
    This study of 27 patients with multiple brain metastasis (2-4 in numbers) and 25 mm or less in diameter with known primary tumors were randomly assigned to WBRT alone or with radiosurgery.
          
    The local failure rate at 1 year was 100% in patients undergoing WBRT and only 8% in patients undergoing WBRT + radiosurgery and median time to local failure was also much better with combined WBRT + radiosurgery (6 months v/s 36 months).
         
    And tumor control of the disease especially in patients with brain metastases (2-4) was better with combined WBRT and radiosurgery than with WBRT alone.
          

  • Shafron DH, Friedman WA, Buatti JM, et al (Univ of Florida, Gainesville)
    LINAC Radiosurgery for Benign Meningiomas
    Int J Radiat Oncol Biol Phys 43: 321-327, 1999
          
    This study of 70 patients with benign meningiomas of which 32 had failed previous surgery and one had received radiotherapy earlier.
         
    LINAC-based radiosurgery for benign meningiomas provided 100% local control and that was maintained during an average follow-up of 23 months.
          

  • Franciosi V, Cocconi G, Michiara M, et al (Azienda Ospedaliera di Parma, Italy, et al)
    Front-line Chemotherapy With Cisplatin and Etoposide for Patients With Brain Metastases From Breast Carcinoma, Nonsmall Cell Lung Carcinoma, or Malignant Melanoma: A Prospective Study
    Cancer 85: 1599-1605, 1999
          
    A previous study had revealed that the combination of cisplatinum and etoposide are highly active against brain metastases from breast carcinoma.
          
    This study of 116 patients treated with front line cisplatinum 100 mg/m2 day 1, and etoposide 100 mg/m2 on days 1, 3 and 5 or on days 4, 6 and 8 every 3 weeks had brain metastasis from breast carcinoma (BC) in 52%, NSCLC in 40% and malignant melanoma (MM) in 8%.
         
    Almost 40% of patients with breast cancer had response and 30% with lung cancer. The median survival rates for patients with BC, NSCLC, and MM were 31 weeks, 32 weeks, and 17 weeks respectively.
           
    The editor comments that these figures would suggest the use of chemotherapy more frequently than earlier in patients with brain metastasis from BC and NSCLC.
        

  • Jeffrey S. Weinberg, Frederick F. Lang, and Raymond Sawaya (Department of Neurosurgery, University of Texas, Anderson Cancer Center, Houston, USA)
    Surgical Management of Brain Metastases 
    Current Oncology Reports Vol. 3(6) November 2001 Pg. 476-483
            
    Systemic malignancies with high propensity to involve the brain are lung, breast, kidney, colon, and melanoma with improved therapy for systemic malignancies, the incidence of metastasis brain tumor is increasing.
         
    The indications for surgical intervention in a patient with suspected brain metastasis are tissue diagnosis, relieve tumor mass effect, decrease tumor burden and provide local cure.
          
    Surgical resection of single brain metastasis followed by WBRT is superior to only WBRT. Most of such cases die from progression of systemic disease rather than brain metastasis. The other important factors for surgical resection are functioning status of the patient, Karnofsky performance status (KPS) of 70 or higher, neurological deficit and earlier response to steroids and those with short expectancy (less than 3 months). Other important factors prior to consideration of surgery include the histology of the tumor for example lymphomas, germinoma and small-cell lung carcinoma are radiosensitive and tumor is optimally treated with radiation.
          
    Surgical resection of multiple metastatic lesions if accomplished by resection of all this masses an improved prognosis can be expected. Radiation following surgery depends on the radiosensitivity for example in non-small cell lung cancer those who received WBRT had a definite decrease in rate of metastasis as compared to melanoma and colon.
           
    Stereotactic radiosurgery involved multiple weak, well-collimated beams of ionizing radiation focussed by stereotaxy on the metastatic lesion. Only lesions less than 3 cm can be treated and no histologic verification is possible. In a single brain metastasis radiosurgery was at least as effective as resection and WBRT whereas results are not favorable for radiosurgery if multiple metastasis.
          
    The other approach by some investigators is to include radiosurgery as a part of multimodality therapy for patients with multiple brain metastasis.
                  

  • John C. Flickinger (Departments of Radiation Oncology and Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, USA)
    Radiotherapy and Radiosurgical Management of Brain Metastases
    Current Oncology Reports Vol. 3(6) November 2001 Pg. 484-489
           
    Whole brain radiotherapy (WBRT) has been the standard and definitive therapy for brain metastasis. 50% of the patients show symptomatic improvement. Median survival of such patients is 4-6 months. Acute side effects such as tiredness, hair loss, and skin redness are well known.
          
    The other side effects such as cognitive function deterioration and declining IQ scores in young children have to be considered. In patients with small-cell lung cancer abnormal neuropsychological and mental status test noted. The conventional fractionated WBRT for multiple brain metastasis has a recurrence rate of 100%.
          
    Radiosurgery has emerged an important therapeutic intervention for controlling brain metastasis which are small to moderate size (<4 cm) and has emerged equal or surpass rates with surgery and WBRT. 
         
    Those patients with single brain metastasis radiosurgery alone is an effective therapy. In those with multiple brain metastasis one reasonable option is surgery in a single dominant hemorrhagic metastasis and radiosurgery to other unresected brain metastasis before wound healing have progressed enough to start WBRT. 
         
    The acute toxicity of radiosurgery are seizures, puffy eyes and delayed neurological toxicity are also of concern.      
                                                                                               

  • Charles A. Conrad (Department of Neuro-Oncology, University of Texas M. D., Anderson Cancer Center, Houston, USA)
    Chemotherapy for Metastatic Tumors to the Central Nervous System   
    Current Oncology Reports Vol. 3(6) November 2001 Pg. 490-494   
                                           
    Metastatic tumor to brain are commonly from primary lung cancer (small-cell and non-small-cell) malignant melanoma, renal cell carcinoma and colorectal cancer.        
                                                
    The perception of poor effectiveness of chemotherapy in metastatic brain disease (MBD) are impaired delivery of chemotherapy due to impenetrability of the blood-brain barrier (BBB), drug resistance of solid tumor clones and the fact that brain metastasis occurs in the setting of drug failure.             
                                           
    Micrometastatic foci do not cause break in BBB however increasing metastatic lesion abrogate the BBB. The current consensus is that although the role of BBB has importance in harboring the microscopic tumor foci.    
                               
    The overall impediment it has on treatment failure is questionable. This is supported by clinical data when response in patients with brain metastasis from chemosensitive tumors such as SCLC or chorio carcinoma are known with combination chemotherapy. Some tumors that have predilection (tropism) for brain metastasis have intrinsic resistance to chemotherapy such as melanoma, renal cell carcinoma. The mechanism of cell survival and other signal transduction mediated pathways involves growth factors, such as VEGF, mutated p53 may play a role.    
                                              
    The other form of resistance to primary chemotherapy and thereby having brain metastases would have a group of cells, which preferably favor growth of drug resistant clones.        
                                                  
    Recently large series have begun to demonstrate positive impact of chemotherapy for patients with selected group of patients with brain metastasis. The role of CDDP followed by vinorelbine and docetaxel in NSCLC patients with brain metastasis and the effect of teniposide in SCLC was not different from lesions in other metastatic sites.           
     

 

 

 

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