Brain metastases outcome

Brain metastases outcome

Overall prognosis depends on ageextent and activity of the systemic disease, number of brain metastases and performance status. In about half of the patients, especially those with widespread and uncontrolled systemic malignancy, death is heavily related to extra-neural lesions, and treatment of cerebral disease doesn’t significantly improve survival.

In such patients the aim is to improve or stabilize the neurological deficit and maintain quality of lifeCorticosteroids and whole brain radiotherapy usually fulfill this purpose. By contrast, patients with limited number of brain metastases, good performance status and controlled or limited systemic disease, may benefit from aggressive treatment as both quality of life and survival are primarily related to treatment of brain lesions.

Strong positive prognostic factors include good functional status, age <65 years, no sites of metastasis outside of the central nervous system (CNS), controlled primary tumor 1), the presence of a single metastasis in the brain, long interval from primary diagnosis to brain relapse, and certain cancer subtypes such as HER2 positive breast cancer brain metastasesand EGFR Non small cell lung cancer intracranial metastases (NSCLC) 2) 3) 4)

Recursive partitioning analysis class

http://rcalc.ccf.org, under the category “Brain Cancer” 5).

In a study of the Royal North Shore Hospital, on univariate analysis, number of metastases (P = 0.04), symptomatic extracranial disease (P = 0.04) and early CNS relapse within 6 months (P < 0.01) had worse survival. No grade 3-4 toxicityevents were noted in 129 patients undergoing RT 6).


It is presently unknown whether patients with brain metastases from heavily pre-treated cancers have a significantly different prognosis than those with less pre-treatment 7).

References

1)

Gaspar L, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997;37:745–751.
2)

Melisko ME, Moore DH, Sneed PK, De Franco J, Rugo HS. Brain metastases in breast cancer: clinical and pathologic characteristics associated with improvements in survival. J Neurooncol. 2008;88:359–365.
3)

Eichler AF, et al. Survival in patients with brain metastases from breast cancer: the importance of HER-2 status. Cancer. 2008;112:2359–2367.
4)

Eichler AF, et al. EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer. Neuro Oncol. 2010;12:1193–1199.
5)

Barnholtz-Sloan JS, Yu C, Sloan AE, Vengoechea J, Wang M, Dignam JJ, Vogelbaum MA, Sperduto PW, Mehta MP, Machtay M, Kattan MW. A nomogram for individualized estimation of survival among patients with brain metastasis. Neuro Oncol. 2012 Jul;14(7):910-8. doi: 10.1093/neuonc/nos087. Epub 2012 Apr 27. PubMed PMID: 22544733; PubMed Central PMCID: PMC3379797.
6)

Or M, Jayamanne D, Guo L, Stevens M, Parkinson J, Cook R, Little N, Back M. Focal radiation therapy for limited brain metastases is associated with high rates of local control and low subsequent whole brain radiation therapy. ANZ J Surg. 2019 Mar 5. doi: 10.1111/ans.15040. [Epub ahead of print] PubMed PMID: 30836451.
7)

Lanier CM, McTyre E, LeCompte M, Cramer CK, Hughes R, Watabe K, Lo HW, O’Neill S, Munley MT, Laxton AW, Tatter SB, Ruiz J, Chan MD. The number of prior lines of systemic therapy as a prognostic factor for patients with brain metastases treated with stereotactic radiosurgery: Results of a large single institution retrospective analysis. Clin Neurol Neurosurg. 2017 Dec 27;165:24-28. doi: 10.1016/j.clineuro.2017.12.021. [Epub ahead of print] PubMed PMID: 29289917.

Gamma Knife Radiosurgery for trigeminal neuralgia outcome

Gamma Knife Radiosurgery for trigeminal neuralgia outcome

Significant pain reduction after initial SRS: 80–96% 1) 2) 3) 4) but only ≈ 65% become pain free. Median latency to pain relief: 3 months (range: 1 d-13 months) 5).

Recurrent pain occurs within three years in 10–25%. Patients with TN and multiple sclerosis are less likely to respond to SRS than those without MS. SRS can be repeated, but only after four months following the original procedure.

Favorable prognosticators: higher radiation doses, previously unoperated patient, absence of atypical pain component, normal pre-treatment sensory function 6).

Side effects: Hypesthesia occurred in 20% after initial SRS, and in 32% of those requiring repeat treatment 7) (higher rates associated with higher radiation doses) 8).


Outcome prediction of this modality is very important for proper case selection. The aim of a study was to create artificial neural networks (ANN) to predict the clinical outcomes after gamma knife radiosurgery (GKRS) in patients with TN, based on preoperative clinical factors.

They used the clinical findings of 155 patients who were underwent GKRS (from March 2000 to march 2015) at Iran Gamma Knife center, TehranIran. Univariate analysis was performed for a long list of risk factors, and those with P-Value < 0.2 were used to create back-propagation ANN models to predict pain reduction and hypoesthesia after GKRS. Pain reduction was defined as BNI score 3a or lower and hypoesthesia was defined as BNI score 3 or 4.

Typical trigeminal neuralgia (TTN) (P-Value = 0.018) and age>65 (P-Value = 0.040) were significantly associated with successful pain reduction and three other variables including radiation dosage >85 (P-Value = 0.098), negative history of diabetes mellitus (P-Value = 0.133) and depression (P-Value = 0.190). On the other hand, radio dosage > 85 (P-Value = 0.008) was significantly associated with hypoesthesia, other related risk factors (with p-Value < 0.2), were history of multiple sclerosis (P-Value = 0.106), pain duration more than 10 years before GKRS (P-Value = 0.115), history of depression (P-Value = 0.139), history of percutaneous ablative procedures (P-Value = 0.148) and history of diabetes mellitus (P-Value = 0.169).ANN models could predict pain reduction and hypoesthesia with the accuracy of 84.5% and 91.5% respectively. By mutual elimination of each factor in this model we could also evaluate the contribution of each factor in the predictive performance of ANN.

The findings show that artificial neural networks can predict post operative outcomes in patients who underwent GKRS with a high level of accuracy. Also the contribution of each factor in the prediction of outcomes can be determined using the trained network 9).

Case series

The long-term results in 130 patients who underwent radiosurgery for classical TN and were subsequently monitored through at least 7 years (median = 9.9, range = 7-14.5) of follow-up.

The median age was 66.5 years. A total of 122 patients (93.8%) became pain free (median delay = 15 days) after the radiosurgery procedure (Barrow Neurological Institute, BNI class I-IIIa). The probability of remaining pain free without medication at 3, 5, 7 and 10 years was 77.9, 73.8, 68 and 51.5%, respectively. Fifty-six patients (45.9%) who were initially pain free experienced recurrent pain (median delay = 73.1 months). However, at 10 years, of the initial 130 patients, 67.7% were free of any recurrence requiring new surgery (BNI class I-IIIa). The new hypesthesia rate was 20.8% (median delay of onset = 12 months), and only 1 patient (0.8%) reported very bothersome hypesthesia.

The long-term results were comparable to those from our general series (recently published), and the high probability of long-lasting pain relief and rarity of consequential complications of radiosurgery may suggest it as a first- and/or second-line treatment for classical, drug-resistant TN 10).


Thirty-six consecutive patients with medically intractable TN received a median radiation dose of 45 Gy applied with a single 4-mm isocenter to the affected trigeminal nerve. Follow-up data were obtained by clinical examination and telephone questionnaire. Outcome results were categorized based on the Barrow Neurological Institute (BNI) pain scale with BNI I-III considered to be good outcomes and BNI IV-V considered as treatment failure. BNI facial numbness score was used to assess treatment complications.

The incidence of early pain relief was high (80.5 %) and relief was noted in an average of 1.6 months after treatment. At minimum follow-up of 3 years, 67 % were pain free (BNI I) and 75 % had good treatment outcome. At a mean last follow-up of 69 months, 32 % were free from any pain and 63 % were free from severe pain. Bothersome posttreatment facial numbness was reported in 11 % of the patients. A statistically significant correlation was found between age and recurrence of any pain with age >70 predicting a more favorable outcome after radiosurgery.

The success rate of GKRS for treatment of medically intractable TN declines over time with 32 % reporting ideal outcome and 63 % reporting good outcome. Patients older than age 70 are good candidates for radiosurgery. This data should help in setting realistic expectations for weighing the various available treatment options 11).


From 1994 to 2009, 40 consecutive patients with typical, intractable TN received GKRS. Among these, 22 patients were followed for >60 months. The mean maximum radiation dose was 77.1 Gy (65.2-83.6 Gy), and the 4 mm collimator was used to target the radiation to the root entry zone.

The mean age was 61.5 years (25-84 years). The mean follow-up period was 92.2 months (60-144 months). According to the pain intensity scale in the last follow-up, 6 cases were grades I-II (pain-free with or without medication; 27.3%) and 7 cases were grade IV-V (<50% pain relief with medication or no pain relief; 31.8%). There was 1 case (facial dysesthesia) with post-operative complications (4.54%).

The long-term results of GKRS for TN are not as satisfactory as those of microvascular decompression and other conventional modalities, but GKRS is a safe, effective and minimally invasive technique which might be considered a first-line therapy for a limited group of patients for whom a more invasive kind of treatment is unsuitable 12).


Kondziolka et al., evaluated pain relief and treatment morbidity after trigeminal neuralgia radiosurgery.

All evaluable patients (n = 106) had medically or surgically refractory trigeminal neuralgia. A single 4-mm isocenter of radiation was focused on the proximal trigeminal nerve just anterior to the pons. For follow-up an independent physician who was unaware of treatment parameters contacted all patients.

After radiosurgery, 64 patients (60%) became free of pain and required no medical therapy (excellent result), 18 (17%) had a 50% to 90% reduction (good result) in pain severity or frequency (some still used medications), and 9 (9%) had slight improvement. At last follow-up (median, 18 months; range, 6-48 months), 77% of patients maintained significant relief (good plus excellent results). Only 6 (10%) of 64 patients who initially attained complete relief had some recurrent pain. Radiosurgery dose (70-90 Gy), age, surgical history, or facial sensory loss did not correlate with pain relief. Poorer results were found in patients with multiple sclerosis. Twelve patients developed new or increased facial paresthesias after radiosurgery (10%). No patient developed anesthesia dolorosa. There was no other procedural morbidity.

Gamma knife radiosurgery is a minimally invasive technique to treat trigeminal neuralgia. It is associated with a low risk of facial paresthesias, an approximate 80% rate of significant pain relief, and a low recurrence rate in patients who initially attain complete relief. Longer-term evaluations are warranted 13).

References

1)

Brisman R. Gamma knife surgery with a dose fo 75 to 76.8 Gray for trigeminal neuralgia. J Neurosurg. 2004; 100:848–854
2) , 8)

Pollock BE, Phuong LK, Foote RL, Sta ord SL, Gor- man DA. High-dose trigeminal neuralgia radiosur- gery associated with increased risk of trigeminal nerve dysfunction. Neurosurgery. 2001; 49:58–62; discussion 62-4
3)

Kondziolka D, Lunsford LD, Flickinger JC. Stereotactic radiosurgery for the treatment of trigeminal neuralgia. Clin J Pain. 2002; 18:42–47
4)

Massager N, Lorenzoni J, Devriendt D, Desmedt F, Brotchi J, Levivier M. Gamma knife surgery for idi- opathic trigeminal neuralgia performed using a far-anterior cisternal target and a high dose of radiation. J Neurosurg. 2004; 100:597–605
5) , 7)

Urgosik D, Liscak R, Novotny J, Jr, Vymazal J, Vlady- 1982 ka V. Treatment of essential trigeminal neuralgia with gamma knife surgery.JNeurosurg.2005; 102 Suppl:29–33
6)

Maesawa S, Salame C, Flickinger JC, Pirris S, Kond- ziolka D, Lunsford LD. Clinical outcomes after ster- eotactic radiosurgery for idiopathic trigeminal neuralgia. J Neurosurg. 2001; 94:14–20
9)

Ertiaei A, Ataeinezhad Z, Bitaraf M, Sheikhrezaei A, Saberi H. Application of an artificial neural network model for early outcome prediction of gamma knife radiosurgery in patients with trigeminal neuralgia and determining the relative importance of risk factors. Clin Neurol Neurosurg. 2019 Feb 12;179:47-52. doi: 10.1016/j.clineuro.2018.11.007. [Epub ahead of print] PubMed PMID: 30825722.
10)

Régis J, Tuleasca C, Resseguier N, Carron R, Donnet A, Yomo S, Gaudart J, Levivier M. The Very Long-Term Outcome of Radiosurgery for Classical Trigeminal Neuralgia. Stereotact Funct Neurosurg. 2016;94(1):24-32. doi: 10.1159/000443529. Epub 2016 Feb 17. PubMed PMID: 26882097.
11)

Karam SD, Tai A, Wooster M, Rashid A, Chen R, Baig N, Jay A, Harter KW, Randolph-Jackson P, Omogbehin A, Aulisi EF, Jacobson J. Trigeminal neuralgia treatment outcomes following Gamma Knife radiosurgery with a minimum 3-year follow-up. J Radiat Oncol. 2014;3:125-130. Epub 2013 Nov 20. PubMed PMID: 24955219; PubMed Central PMCID: PMC4052001.
12)

Lee JK, Choi HJ, Ko HC, Choi SK, Lim YJ. Long term outcomes of gamma knife radiosurgery for typical trigeminal neuralgia-minimum 5-year follow-up. J Korean Neurosurg Soc. 2012 May;51(5):276-80. doi: 10.3340/jkns.2012.51.5.276. Epub 2012 May 31. PubMed PMID: 22792424; PubMed Central PMCID: PMC3393862.
13)

Kondziolka D, Perez B, Flickinger JC, Habeck M, Lunsford LD. Gamma knife radiosurgery for trigeminal neuralgia: results and expectations. Arch Neurol. 1998 Dec;55(12):1524-9. PubMed PMID: 9865796.

Traumatic cervical spinal cord injury outcome

Injury to the spine and spinal cord is one of the common cause of disability and death. Several factors affect the outcome; but which are these factors (alone and in combination), are determining the outcomes are still unknown.

Based on parameters from the International Standards, physicians are able to inform patients about the predicted long-term outcomes, including the ability to walk, with high accuracy. In those patients who cannot participate in a reliable physical neurological examination, magnetic resonance imaging and electrophysiological examinations may provide useful diagnostic and prognostic information. As clinical research on this topic continues, the prognostic value of the reviewed diagnostic assessments will become more accurate in the near future. These advances will provide useful information for physicians to counsel tSCI patients and their families during the catastrophic initial phase after the injury 1).

Preclinical and class III clinical data suggest improved outcomes by maintaining the mean arterial pressure > 85 mm Hg and avoiding hypoxemia at least for 7 days following cervical SCI, and this level of monitoring and support should occur in the ICU 2).


100 cases of patients under 18 years at accident with acute traumatic cervical spinal cord injury admitted to spinal cord injury SCI centers participating in the European Multi-center study about SCI (EMSCI) between January 2005 and April 2016 were reviewed. According to their age at accident, age 13 to 17, patients were selected for the adolescent group. After applying in- and exclusion criteria 32 adolescents were included. Each adolescent patient was matched with two adult SCI patients for analysis.

ASIA Impairment scale (AIS) grade, neurological, sensory, motor level, total motor score, and Spinal Cord Independence Measure (SCIM III) total score.

Mean AIS conversion, neurological, motor and sensory levels as well as total motor score showed no significantly statistical difference in adolescents compared to the adult control group after follow up of 6 months. Significantly higher final SCIM scores (p < 0.05) in the adolescent group compared to adults as well as a strong trend for a higher gain in SCIM score (p < 0.061) between first and last follow up was found.

Neurological outcome after traumatic cervical SCI is not superior in adolescents compared to adults in this cohort. Significantly higher SCIM scores indicate more functional gain for the adolescent patients after traumatic cervical SCI. Juvenile age appears to be an independent predictor for a better functional outcome. 3).


A prospective observational study at single-center with all patients with cervical spinal cord injury (SCI), attending our hospital within a week of injury during a period of October 2011 to July 2013 was included for analysis. Demographic factors such as age, gender, etiology of injury, preoperative American Spinal Injury Association (ASIA) grade, upper (C2-C4) versus lower (C5-C7) cervical level of injury, imageological factors on magnetic resonance imaging (MRI), and timing of intervention were studied. Change in neurological status by one or more ASIA grade from the date of admission to 6 months follow-up was taken as an improvement. Functional grading was assessed using the functional independence measure (FIM) scale at 6 months follow-up.

A total of 39 patients with an acute cervical spine injury, managed surgically were included in this study. Follow-up was available for 38 patients at 6 months. No improvement was noted in patients with ASIA Grade A. Maximum improvement was noted in ASIA Grade D group (83.3%). The improvement was more significant in lower cervical region injuries. Patient with cord contusion showed no improvement as opposed to those with just edema wherein; the improvement was seen in 62.5% patients. Percentage of improvement in cord edema ≤3 segments (75%) was significantly higher than edema with >3 segments (42.9%). Maximum improvement in FIM score was noted in ASIA Grade C and patients who had edema (especially ≤3 segments) in MRI cervical spine.

Complete cervical SCI, upper-level cervical cord injury, patients showing MRI contusion, edema >3 segments group have worst improvement in neurological status at 6 months follow-up 4).


A total of 66 patients diagnosed with traumatic cervical SCI were selected for neurological assessment (using the International standards for neurological classification of spinal cord injury [ISNCSCI]) and functional evaluation (based on the Korean version Modified Barthel Index [K-MBI] and Functional Independence Measure [FIM]) at admission and upon discharge. All of the subjects received a preliminary electrophysiological assessment, according to which they were divided into two groups as follows: those with cervical radiculopathy (the SCI/Rad group) and those without (the SCI group).

A total of 32 patients with cervical SCI (48.5%) had cervical radiculopathy. The initial ISNCSCI scores for sensory and motor, K-MBI, and total FIM did not significantly differ between the SCI group and the SCI/Rad group. However, at discharge, the ISNCSCI scores for motor, K-MBI, and FIM of the SCI/Rad group showed less improvement (5.44±8.08, 15.19±19.39 and 10.84±11.49, respectively) than those of the SCI group (10.76±9.86, 24.79±19.65 and 17.76±15.84, respectively) (p<0.05). In the SCI/Rad group, the number of involved levels of cervical radiculopathy was negatively correlated with the initial and follow-up motors score by ISNCSCI.

Cervical radiculopathy is not rare in patients with traumatic cervical SCI, and it can impede neurological and functional improvement. Therefore, detection of combined cervical radiculopathy by electrophysiological assessment is essential for accurate prognosis of cervical SCI patients in the rehabilitation unit 5).

References

1)

van Middendorp JJ, Goss B, Urquhart S, Atresh S, Williams RP, Schuetz M. Diagnosis and prognosis of traumatic spinal cord injury. Global Spine J. 2011 Dec;1(1):1-8. doi: 10.1055/s-0031-1296049. PubMed PMID: 24353930; PubMed Central PMCID: PMC3864437.
2)

Schwartzbauer G, Stein D. Critical Care of Traumatic Cervical Spinal Cord Injuries: Preventing Secondary Injury. Semin Neurol. 2016 Dec;36(6):577-585. Epub 2016 Dec 1. Review. PubMed PMID: 27907962.
3)

Geuther M, Grassner L, Mach O, Klein B, Högel F, Voth M, Bühren V, Maier D, Abel R, Weidner N, Rupp R, Fürstenberg CH; EMSCI study group, Schneidmueller D. Functional outcome after traumatic cervical spinal cord injury is superior in adolescents compared to adults. Eur J Paediatr Neurol. 2018 Dec 11. pii: S1090-3798(18)30247-2. doi: 10.1016/j.ejpn.2018.12.001. [Epub ahead of print] PubMed PMID: 30579697.
4)

Srinivas BH, Rajesh A, Purohit AK. Factors affecting outcome of acute cervical spine injury: A prospective study. Asian J Neurosurg. 2017 Jul-Sep;12(3):416-423. doi: 10.4103/1793-5482.180942. PubMed PMID: 28761518; PubMed Central PMCID: PMC5532925.
5)

Kim SY, Kim TU, Lee SJ, Hyun JK. Prognosis for patients with traumatic cervical spinal cord injury combined with cervical radiculopathy. Ann Rehabil Med. 2014 Aug;38(4):443-9. doi: 10.5535/arm.2014.38.4.443. Epub 2014 Aug 28. PubMed PMID: 25229022; PubMed Central PMCID: PMC4163583.
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