Medulloblastoma outcome

Medulloblastoma outcome

All medulloblastomas are WHO grade IV.

Poor prognosticators

● younger age (especially if<3 yrs)

● disseminated (metastatic) disease

● inability to perform gross-total removal(especially if residual > 1.5cm2 in patient with localized disease)

● histological differentiation along glial, ependymal, or neuronal lines

Medulloblastoma is the most common malignant brain tumor that occurs during childhood. Multimodality treatment regimens have substantially improved survival in this disease; however, the tumour is incurable in about a third of patients with medulloblastoma, and current treatment has a detrimental effect on long-term survivors. Drugs that target cell-signaling pathways provide an alternative to conventional cytotoxic approaches to the treatment of cancer. Several pathways have been implicated in medulloblastoma formation, and knowledge of these is now being used to develop new ways of treating children with medulloblastoma 1).

Weil et al. 2) and Prados et al. 3) found female gender to be a significant favorable prognostic factor in medulloblastoma. Sex did not reveal any bearing on the outcome in the series of Kumar et al. 4).

Age, hemispheric location of the tumor, the extent of resection, and adjuvant therapy status were the important clinical prognostic factors for survival in the series of Narayan et al. 5).

Complete resection should be performed if possible as several studies have correlated outcome with the extent of resection and amount of residual tumor 6).

Gene expression profiling is highly predictive of response to therapy, predicting outcome with much greater accuracy than current staging criteria 7).

Long-term survivors of MB are at significant risk for permanent endocrinologic, cognitive, and psychological sequelae of treatments. Infants and very young children with MB remain a di cult therapeutic challenge because they have the most virulent form of the disease and are at the highest risk for treatment-related sequelae. Most common site of recurrence is p-fossa. Collins’law has also been used to define the period of the risk of recurrence (PRR) but exceptions to the law have been reported 8).


Ninety-seven samples of medulloblastoma were collected. Tumor content in samples was judged by frozen section review. Tumor ERBB2 protein and MYCC, MYCN, and TRKC mRNA levels were measured blind to clinical details using Western blotting and real-time polymerase chain reaction, respectively. Histopathologic and clinical review of each case was also performed. All data were subjected to independent statistical analysis.

Sample acquisition and analysis times ranged from 3 to 6 days. Eighty-six samples contained sufficient tumor for analysis, including 38 classic, 30 nodular desmoplastic, and 18 large-cell anaplastic (LCA) medulloblastomas. Protein and mRNA were extracted from 81 and 49 tumors, respectively. ERBB2 was detected in 40% (n=32 of 81) of tumors, most frequently in LCA disease (P=.005), and was independently associated with a poor prognosis (P=.031). A combination of clinical characteristics and ERBB2 expression provided a highly accurate means of discriminating disease risk. One hundred percent (n=26) of children with clinical average-risk, ERBB2-negative disease were alive at 5 years, with a median follow-up of 5.6 years, compared with only 54% for children with average-risk, ERBB2-positive tumors (n=13; P=.0001). TRKC, MYCC, and MYCN expression and histopathologic subtype were not associated with prognosis in this study.

Central and rapid molecular analysis of frozen medulloblastomas collected from multiple institutions is feasible. ERBB2 expression and clinical risk factors together constitute a highly accurate disease risk stratification tool 9).


The purpose of a study of was to determine the relative contributions of biological and clinical predictors of survival in patients with medulloblastoma (MB).

Clinical presentation and survival information were obtained for 119 patients who had undergone surgery for MB at the Hospital for Sick Children (Toronto, Ontario, Canada) between 1985 and 2001. A tissue microarray was constructed from the tumor samples. The arrays were assayed for immunohistochemical expression of MYC, p53, platelet-derived growth factor receptor-alpha, ErbB2, MIB-1, and TrkC and for apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling). Both univariable and multivariable analyses were conducted to characterize the association between survival and both clinical and biological markers. For the strongest predictors of survival, a weighted predictive score was calculated based on their hazard ratios (HRs). The sum of these scores was then used to give an overall prediction of survival using a nomogram.

The four strongest predictors of survival in the final multivariable model were the presence of metastatic disease at presentation (HR, 2.02; P=0.01) and p53 (HR, 2.29; P=0.02), TrkC (HR, 0.65; P=0.14), and ErbB2 (HR, 1.51; P=0.21) immunopositivity. A linear prognostic index was derived, with coefficients equal to the logarithm of these HRs. The 5-year survival rate for patients at the 10th, 50th, and 90th percentiles of the score distribution was 80.0%, 71.0%, and 35.7%, respectively, with radiation therapy and 70.5%, 58.5%, and 20.0%, respectively, without radiation therapy.

In this study, we demonstrate an approach to combining both clinical and biological markers to quantify risk in MB patients. This provides further prognostic information than can be obtained when either clinical factors or biological markers are studied separately and establishes a framework for comparing prognostic markers in future clinical studies 10).


Two rare subtypes at extreme ends of the histologic spectrum, i.e., medulloblastomas with extensive nodularity and large cell/anaplastic medulloblastomas, are associated with better and worse clinical outcomes, respectively. However, there is little data about correlations between histologic features and clinical outcomes for most patients with medulloblastomas that fall between these histologic extremes of nodularity and anaplasia.

Eberhart et al. evaluated the clinical effects of increasing anaplasia and nodularity in a large group of children with medulloblastomas, hypothesizing that increasing nodularity would predict better clinical outcomes and that increasing anaplasia would presage less favorable results.

Medulloblastomas from 330 Pediatric Oncology Group patients were evaluated histologically with respect to extent of nodularity, presence of desmoplasia, grade of anaplasia, and extent of anaplasia. Pathologic and clinical data were then compared using Kaplan-Meier and log-rank analyses.

Increasing grade of anaplasia and extent of anaplasia were associated strongly with progressively worse clinical outcomes (P < 0.0001 for both). Significant anaplasia (moderate or severe) was identified in 24% of medulloblastoma specimens. Neither increasing degrees of nodularity nor desmoplasia were associated significantly with longer survival.

Moderate anaplasia and severe anaplasia were associated with aggressive clinical behavior in patients with medulloblastomas and were detected in a significant number of specimens (24%). Pathologic grading of medulloblastomas with respect to anaplasia may be of clinical utility 11).


Although surgery, radiation and high-dose chemotherapy have led to increased survival, one-third of patients succumb to their disease, and patients who survive suffer severe long-term side effects as a consequence of treatment.

Through analysis of several well-designed multi-institutional trials, much has been learned about the clinical factors that influence outcome in children with medulloblastomas. Age younger than 3 years, bulky residual disease postoperatively, and metastasis constitute adverse prognostic features and indicate patients who are considered “high risk” for recurrence with standard therapy using 3600 cGy craniospinal radiation in conjunction with a posterior fossa dose of 5400 cGy. Patients lacking these features are considered “standard risk.”

Evaluation of biologic predictors of outcome, which may further refine treatment stratification, is in progress.

References

1)

Gilbertson RJ. Medulloblastoma: signalling a change in treatment. Lancet Oncol. 2004; 5:209–218
2)

Weil MD, Lamborn K, Edwards MS, Wara WM. Influence of a child’s sex on medulloblastoma outcome. JAMA. 1998 May 13;279(18):1474-6. PubMed PMID: 9600483.
3)

Prados MD, Warnick RE, Wara WM, Larson DA, Lamborn K, Wilson CB. Medulloblastoma in adults. Int J Radiat Oncol Biol Phys. 1995 Jul 15;32(4):1145-52. PubMed PMID: 7607936.
4)

Kumar LP, Deepa SF, Moinca I, Suresh P, Naidu KV. Medulloblastoma: A common pediatric tumor: Prognostic factors and predictors of outcome. Asian J Neurosurg. 2015 Jan-Mar;10(1):50. doi: 10.4103/1793-5482.151516. PubMed PMID: 25767583; PubMed Central PMCID: PMC4352636.
5)

Narayan V, Sugur H, Jaiswal J, Arvinda HR, Arivazhagan A, Somanna S, Santosh V. Medulloblastoma: Distinctive Histo-Molecular Correlation with Clinical Profile, Radiologic Characteristics, and Surgical Outcome. Pediatr Neurosurg. 2019 Sep 3:1-12. doi: 10.1159/000501913. [Epub ahead of print] PubMed PMID: 31480064.
6)

Chatty EM, Earle KM. Medulloblastoma. A report of 201 cases with emphasis on the relationship of histologic variants to survival. Cancer. 1971 Oct;28(4):977-83. PubMed PMID: 5111749.
7)

Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, Kim JY, Goumnerova LC, Black PM, Lau C, Allen JC, Zagzag D, Olson JM, Curran T, Wetmore C, Biegel JA, Poggio T, Mukherjee S, Rifkin R, Califano A, Stolovitzky G, Louis DN, Mesirov JP, Lander ES, Golub TR. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature. 2002 Jan 24;415(6870):436-42. PubMed PMID: 11807556.
8)

Sure U, Berghorn WJ, Bertalan y H. Collins’ law. Prediction of recurrence or cure in childhood medulloblastoma? Clin Neurol Neurosurg. 1997; 99:113–116
9)

Gajjar A, Hernan R, Kocak M, Fuller C, Lee Y, McKinnon PJ, Wallace D, Lau C, Chintagumpala M, Ashley DM, Kellie SJ, Kun L, Gilbertson RJ. Clinical, histopathologic, and molecular markers of prognosis: toward a new disease risk stratification system for medulloblastoma. J Clin Oncol. 2004 Mar 15;22(6):984-93. Epub 2004 Feb 17. PubMed PMID: 14970185.
10)

Ray A, Ho M, Ma J, Parkes RK, Mainprize TG, Ueda S, McLaughlin J, Bouffet E, Rutka JT, Hawkins CE. A clinicobiological model predicting survival in medulloblastoma. Clin Cancer Res. 2004 Nov 15;10(22):7613-20. PubMed PMID: 15569993.
11)

Eberhart CG, Kepner JL, Goldthwaite PT, Kun LE, Duffner PK, Friedman HS, Strother DR, Burger PC. Histopathologic grading of medulloblastomas: a Pediatric Oncology Group study. Cancer. 2002 Jan 15;94(2):552-60. PubMed PMID: 11900240.

Cervical spondylotic myelopathy surgery outcome

Cervical spondylotic myelopathy surgery outcome

see Machine learning for degenerative cervical myelopathy.

Objective scoring of the post-operative neurological function did not correlate with patient-perceived outcomes in Degenerative cervical myelopathy outcome(DCM). Traditional testing of motor and sensory function as part of the neurological assessment may not be sensitive enough to assess the scope of neurological changes experienced by Degenerative cervical myelopathypatients 1).


Hamdan assessed the relation between MRI T2 Weighted images (T2WIhyperintense cord signal and clinical outcome after anterior cervical discectomy in patients with degenerative cervical disc herniation.

This retrospective observational study was conducted on twenty-five patients with degenerative cervical disc prolapse associated with MRI T2WI hyperintense cord signal, at the Department of Neurosurgery, Qena University Hospital, South Valley University from August 2014 to December 2016. A complete clinical and radiological evaluation of the patients was done. Anterior cervical discectomy and fusion was done for all patients. Patients were clinically assessed preoperatively and postoperatively at 3, 6, and 12 months using Modified Japanese Orthopaedic Association scale (MJOA). Radiographic assessment was done by preoperative and postoperative T2WI MRI. The statistical analysis was done using Statistical Package for the Social Sciences (SPSS) software (version 22.0).

There were 25 patients included in the study; 16 (64%) females and 9 (36%) males. The mean age was 46.89 ± 7.52 standard deviation (SD) years with range from 26 to 64 years, 3 (12%) patients had worsened in the form of postoperative motor power deterioration, and 14 (56%) patients has no improvement and remain as preoperative condition. The remaining 8 (32%) patients had a reported postoperative improvement of symptoms and signs according to MJOA score. The mean follow-up period (in months) was 11 ± 2.34 (SD). Conclusion:

The presence of T2W hyperintense signal on preoperative MRI predicts a poor surgical outcome in patients with cervical disc prolapse. The regression of T2W ISI postoperatively correlates with better functional outcomes 2).


Whilst decompressive surgery can halt disease progression, existing spinal cord damage is often permanent, leaving patients with lifelong disability.

Early surgery improves the likelihood of recovery, yet the average time from onset of symptoms to correct diagnosis is over 2 years. The majority of delays occur initially, before and within primary care, mainly due to a lack of recognition. Symptom checkers are widely used by patients before medical consultation and can be useful for preliminary triage and diagnosis. Lack of recognition of Degenerative Cervical Myelopathy (DCM) by symptom checkers may contribute to the delay in diagnosis.

The impact of the changes in myelopathic signs following cervical decompression surgery and their relationship to functional outcome measures remains unclear.

Surgery is associated with a significant quality of life improvement. The intervention is cost effective and, from the perspective of the hospital payer, should be supported 3).

Surgical decompression for CSM is safe and results in improved functional status and quality of life in patients around the world, irrespective of differences in medical systems and socio-cultural determinants of health 4).

The successful management of CSM depends upon an early and accurate diagnosis, an objective assessment of impairment and disability, and an ability to predict outcome. In this field, quantitative measures are increasingly used by clinicians to grade functional and neurological status and to provide decision-making support 5).


In addition, objective assessment tools allow clinicians to quantify myelopathy severity, predict outcome, and evaluate surgical benefits by tracking improvements throughout follow-up 6) 7) 8).

Several outcome measures assess functional impairment and quality of life in patients with cervical myelopathy 9) 10) 11) 12) 13).

A validated “gold standard,” however, has not been established, preventing the development of quantitative guidelines for CSM management 14).

In this field, one of the most widely accepted tool for assessing functional status is the modified Japanese Orthopaedic Association scale (mJOA).

Some studies have found that resolution of T2 hyperintensity in subjects with CSM who undergo ventral decompressive surgery correlates with improved functional outcomes. Other studies have found little correlation with postoperative outcome 15) 16).

References

1)

McGregor SM, Detombe S, Goncalves S, Doyle-Pettypiece P, Bartha R, Duggal N. Does the Neurological Exam Correlate with Patient Perceived Outcomes in Degenerative Cervical Myelopathy? World Neurosurg. 2019 Aug 2. pii: S1878-8750(19)32111-4. doi: 10.1016/j.wneu.2019.07.195. [Epub ahead of print] PubMed PMID: 31382071.
2)

Hamdan ARK. The Relation between Cord Signal and Clinical Outcome after Anterior Cervical Discectomy in Patients with Degenerative Cervical Disc Herniation. Asian J Neurosurg. 2019 Jan-Mar;14(1):106-110. doi: 10.4103/ajns.AJNS_262_17. PubMed PMID: 30937019; PubMed Central PMCID: PMC6417293.
3)

Witiw CD, Tetreault LA, Smieliauskas F, Kopjar B, Massicotte EM, Fehlings MG. Surgery for degenerative cervical myelopathy: a patient centered quality of life and health economic evaluation. Spine J. 2016 Oct 25. pii: S1529-9430(16)31022-1. doi: 10.1016/j.spinee.2016.10.015. [Epub ahead of print] PubMed PMID: 27793760.
4)

Fehlings MG, Ibrahim A, Tetreault L, Albanese V, Alvarado M, Arnold P, Barbagallo G, Bartels R, Bolger C, Defino H, Kale S, Massicotte E, Moraes O, Scerrati M, Tan G, Tanaka M, Toyone T, Yukawa Y, Zhou Q, Zileli M, Kopjar B. A Global Perspective on the Outcomes of Surgical Decompression in Patients with Cervical Spondylotic Myelopathy: Results from the Prospective Multicenter AOSpine International Study on 479 patients. Spine (Phila Pa 1976). 2015 May 27. [Epub ahead of print] PubMed PMID: 26020847.
5) , 14)

Singh A, Tetreault L, Casey A, et al. A summary of assessment tools for patients suffering from cervical spondylotic myelopathy: a systematic review on validity, reliability, and responsiveness [published online ahead of print September 5, 2013]. Eur Spine J. doi:10.1007/s00586-013-2935-x.
6)

Laing RJ. Measuring outcome in neurosurgery. Br J Neurosurg 2000;14:181–4.
7)

Holly LT, Matz PG, Anderson PA, et al. Clinical prognostic indicators of surgical outcome in cervical spondylotic myelopathy. J Neurosurg Spine 2009;11:112–8.
8)

Kalsi-Ryan S, Singh A, Massicotte EM, et al. Ancillary outcome measures for assessment of individuals with cervical spondylotic myelopathy. Spine (Phila Pa 1976) 2013;38:S111–22.
9)

Singh A, Crockard HA. Quantitative assessment of cervical spondylotic myelopathy by a simple walking test. Lancet 1999;354:370–3.
10)

Nurick S. The natural history and the results of surgical treatment of the spinal cord disorder associated with cervical spondylosis. Brain 1972;95:101–8.
11)

Olindo S, Signate A, Richech A, et al. Quantitative assessment of hand disability by the nine-hole-peg test (9-HPT) in cervical spondylotic myelopathy. J Neurol Neurosurg Psychiatry 2008;79:965–7.
12)

Hosono N, Sakaura H, Mukai Y, et al. A simple performance test for quantifying the severity of cervical myelopathy [erratum in: J Bone Joint Surg Br 2008;90:1534]. J Bone Joint Surg Br 2008;90:1210–3.
13)

Casey AT, Bland JM, Crockard HA. Development of a functional scoring system for rheumatoid arthritis patients with cervical myelopathy. Ann Rheum Dis 1996;55:901–6.
15)

Sarkar S, Turel MK, Jacob KS, Chacko AG. The evolution of T2-weighted intramedullary signal changes following ventral decompressive surgery for cervical spondylotic myelopathy. J Neurosurg Spine. 2014;21(4):538-546.
Vedantam A, Rajshekhar V. Change in morphology of intramedullary T2- weighted increased signal intensity after anterior decompressive surgery for cervical spondylotic myelopathy. Spine (Phila Pa 1976). 2014;39(18):1458-1462.

Malignant middle cerebral artery infarction outcome

Malignant middle cerebral artery infarction outcome

Malignant middle cerebral artery infarction is associated with high mortality and morbidity.

The mortality rate of patients with brain edema after malignant middle cerebral artery (MCA) infarction approaches 80 % without surgical intervention 1).

Over the past 10 years in Francedecompressive craniectomy (DC) has been increasingly performed for malignant middle cerebral artery infarction (MCI) regardless of age. However, in-hospital mortality remains considerable, as about one-quarter of patients died within the first weeks. For those who survive beyond 6 months, the risk of death significantly decreases. Early mortality is especially high for comatose patients above 60 years operated in inexperienced centers. Most of those who remain in good functional status tend to undergo a cranioplasty within the year following DC 2).


Three separate studies investigated the effectiveness of decompressive craniectomy after malignant MCA infarction in controlled trials with patients less than 61 years of age 3) 4) 5). These were demonstrated that hemicraniectomy reduced the mortality rate by 49% at one year after stroke when compared with conventional medical treatments. However, the question of how applicable the results are to patients older than 60 years of age still remains unanswered.

When neurosurgeons recommend decompressive surgery for patients with malignant infarcts, patients’ relatives often refuse the operation because of the patients’ age, past medical history or comorbidity. Such a situation occurs more frequently when the patient is older than 70 years of age 6).

References

1)

Huttner HB, Schwab S. Malignant middle cerebral artery infarction: clinical characteristics, treatment strategies, and future perspectives. Lancet Neurol 2009; 8:949–958.
2)

Champeaux C, Weller J. Long-Term Survival After Decompressive Craniectomy for Malignant Brain Infarction: A 10-Year Nationwide Study. Neurocrit Care. 2019 Jul 9. doi: 10.1007/s12028-019-00774-9. [Epub ahead of print] PubMed PMID: 31290068.
3)

Hofmeijer J, Kappelle LJ, Algra A, Amelink GJ, van Gijn J, van der Worp HB, et al. Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial. Lancet Neurol. 2009 Apr;8(4):326–333.
4)

Jüttler E, Schwab S, Schmiedek P, Unterberg A, Hennerici M, Woitzik J, et al. Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial. Stroke. 2007 Sep;38(9):2518–2525.
5)

Vahedi K, Vicaut E, Mateo J, Kurtz A, Orabi M, Guichard JP, et al. Sequential-design, multicenter, randomized, controlled trial of early decompressive craniectomy in malignant middle cerebral artery infarction (DECIMAL Trial) Stroke. 2007 Sep;38(9):2506–2517.
6)

Yu JW, Choi JH, Kim DH, Cha JK, Huh JT. Outcome following decompressive craniectomy for malignant middle cerebral artery infarction in patients older than 70 years old. J Cerebrovasc Endovasc Neurosurg. 2012 Jun;14(2):65-74. doi: 10.7461/jcen.2012.14.2.65. Epub 2012 Jun 30. PubMed PMID: 23210030; PubMed Central PMCID: PMC3471258.
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