title: High-dose Neural Stem Cell Radiation May Not Improve Survival in Glioblastoma.
abstract: OBJECTIVE
  To evaluate the effect of radiotherapy dose-volume parameters of neural stem cell (NSC) compartment on progression-free survival (PFS) and overall survival after post-resection chemoradiation in newly diagnosed glioblastoma.
  
  
  METHODS
  Sixty-one patients with unifocal glioblastoma were included. Ipsilateral (NSC_Ipsi), contralateral (NSC_Contra) and combined NSC (NSC_Combined) were contoured on radiotherapy planning computerised tomography datasets. NSC dose-volume parameters were correlated with PFS and overall survival. Serial magnetic resonance imaging scans were assessed to understand the frequency of pre- and post-treatment involvement of the NSC by contrast enhancing lesions (CELs).
  
  
  RESULTS
  Baseline involvement of NSC with CELs was seen in 67.2% and 95.9% had CELs and FLAIR abnormalities at progression. With a median follow-up of 14.1 months (interquartile range 9.4-20.6 months), median PFS and overall survival were 14.5 (95% confidence interval 11.6-17.5) and 16.2 (95% confidence interval 13.3-19.2) months, respectively. Poor Eastern Cooperative Oncology Group performance score, advanced recursive partitioning analysis class, unmethylated O6-methylguanine methyltransferase (MGMT) status, higher than median of mean NSC_Ipsi dose were associated with significantly inferior PFS and overall survival on univariate analysis. On multivariate analysis, unmethylated MGMT status, higher than median of mean doses to NSC_Ipsi and poor compliance to adjuvant temozolomide were independent predictors of inferior survival.
  
  
  CONCLUSIONS
  In this cohort, 67.2% of newly diagnosed glioblastoma patients had NSC involved with CELs at presentation and 95.9% at progression. This might be an imaging surrogate of the current notion of gliomagenesis and progression from NSC rests. A high radiation dose to NSC_Ipsi was significantly associated with inferior survival. This could be a function of larger tumours and planning target volumes in those with pre-treatment NSC involvement. Methylated MGMT and good compliance to adjuvant temozolomide were independent predictors of better survival. Until further evidence brings hope for glioblastoma, elective, partial NSC irradiation remains experimental.
authors.affiliation: Department of Radiation Oncology, Tata Medical Center, Kolkata, India. Electronic address: rimpaachari@gmail.com.
authors.forename: R
authors.initials: R
authors.lastname: Achari
authors.affiliation: Department of Radiation Oncology, Tata Medical Center, Kolkata, India.
authors.forename: M
authors.initials: M
authors.lastname: Arunsingh
authors.affiliation: Department of Radiation Oncology, Tata Medical Center, Kolkata, India.
authors.forename: R K
authors.initials: RK
authors.lastname: Badgami
authors.affiliation: Department of Radiation Oncology, Tata Medical Center, Kolkata, India.
authors.forename: A
authors.initials: A
authors.lastname: Saha
authors.affiliation: Department of Radiation Oncology, Tata Medical Center, Kolkata, India.
authors.forename: S
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Department of Radiation Oncology, Tata Medical Center, Kolkata, India.
authors.forename: R K
authors.initials: RK
authors.lastname: Shrimali
authors.affiliation: Department of Radiation Oncology, Tata Medical Center, Kolkata, India.
authors.forename: I
authors.initials: I
authors.lastname: Mallick
authors.affiliation: Department of Medical Physics, Tata Medical Center, Kolkata, India.
authors.forename: B
authors.initials: B
authors.lastname: Arun
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant; D003287:Contrast Media; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000628:therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D058953:Neural Stem Cells / Q000528:radiation effects*; D011879:Radiotherapy Dosage; D015996:Survival Rate; D000077204:Temozolomide; D014057:Tomography, X-Ray Computed; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003287:Contrast Media; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide
keywords: Glioblastoma; neural stem cell; radiation therapy; survival