The utility of arterial spin labelled perfusion-weighted magnetic resonance imaging in measuring the vascularity of high grade gliomas - A prospective study.

Background: Dynamic susceptibility contrast (DSC) perfusion weighted imaging (PWI) currently remains the gold standard technique for measuring cerebral perfusion in glioma diagnosis and surveillance. Arterial spin labelling (ASL) PWI is a non-invasive alternative that does not require gadolinium contrast administration, although it is yet to be applied in widespread clinical practice. This study aims to assess the utility of measuring signal intensity in ASL PWI in predicting glioma vascularity by measuring maximal tumour signal intensity in patients based on pre-operative imaging and comparing this to maximal vessel density on histopathology. Methods: Pseudocontinuous ASL (pCASL) and DSC images were acquired pre-operatively in 21 patients with high grade gliomas. The maximal signal intensity within the gliomas over a region of interest of 100 mm2 was measured and also normalised to the contralateral cerebral cortex (nTBF-C), and cerebellum (nTBF-Cb). Maximal vessel density per 1 mm2 was determined on histopathology using CD31 and CD34 immunostaining on all participants. Results: Using ASL, statistically significant correlation was observed between maximal signal intensity (p < 0.05) and nTBF-C (p < 0.05) to maximal vessel density based on histopathology. Although a positive trend was also observed nTBF-Cb, this did not reach statistical significance. Using DSC, no statistically significant correlation was found between signal intensity, nTBF-C and nTBF-Cb. There was no correlation between maximal signal intensity between ASL and DSC. Average vessel density did not correlate with age, sex, previous treatment, or IDH status. Conclusions: ASL PWI imaging is a reliable marker of evaluating the vascularity of high grade gliomas and may be used as an adjunct to DSC PWI.

Cytoreductive Surgery for Primary Central Nervous System Lymphoma: Is it time to consider extent of resection?

BACKGROUND: Cytoreductive surgery for Primary Central Nervous System Lymphoma (PCNSL) is controversial and is not routinely practiced. Cumulative literature in recent years, however, suggests a potential survival benefit associated with a greater extent of resection. METHODS: A retrospective single institution cohort analysis of 58 consecutive patients with PCNSL was conducted between January 2011 and December 2020. Demographic, clinical, and radiographic characteristics were compared between patients with and without cytoreductive surgery following diagnosis of PCNSL. The primary outcome measures were progression-free survival (PFS) and overall survival (OS). Secondary outcome measures included time to remission (TTR), time to chemotherapy (TTC) and response to initial chemotherapy (RIC). RESULTS: Forty-six patients (79.3 %) received stereotactic biopsy and 12 (20.6 %) underwent cytoreductive surgery. There was a trend towards longer OS (29.8 vs 22.3 months, p = 0.672), shorter TTR (4.0 vs 4.7 months, p = 0.362), and greater complete or near-complete radiographic RIC (81.8 % vs 67.6 %, p = 0.367) for patients undergoing cytoreductive surgery. This correlated with a lesser need for whole brain radiotherapy (WBRT) (8.3 % vs 19.6 %, p = 0.359). CONCLUSION: Our data suggests a potential benefit of cytoreductive surgery for selected patients diagnosed with PCNSL. Although not statistically significant, there was a trend towards improved OS, reduced TTR, greater RIC, and reduced WBRT requirement. Further studies with better randomization and statistical power are needed to validate this correlation.

Accurate lesion localisation facilitates nephron sparing surgery in reninoma patients: case report and discussion.

A 21-year-old female was referred with a suspected juxtaglomerular cell tumour (reninoma) in the superior pole of the left kidney. She underwent renal biopsy and renal vein sampling (RVS) to confirm the diagnosis. Following an uncomplicated laparoscopic partial nephrectomy, antihypertensive medications were ceased. Histopathology confirmed the diagnosis. Reninoma is a rare but reversible cause of secondary hypertension and should be considered along with primary hyperaldosteronism and pheochromocytoma when investigating hypertension in a young person. The subtle appearance of reninoma on imaging can necessitate other investigations to confirm the diagnosis. Definitive localisation is essential to prevent unnecessary loss of nephrons.

Molecular confirmation of pathological specimen integrity in Australasia.

AIM: Investigations into 14 suspected pathology sample identification errors and mix-ups were performed, as a service for several public hospital and private laboratories, from 2005 to 2007. METHODS: Analyses were performed with the forensic ABI Identifiler kit of 16 microsatellites (15 autosomal and amelogenin) on DNA from paraffin-embedded tissues or blood specimens and compared to independently verified (single or multiple) patient samples. RESULTS: Of 23 unique patient specimens referred for sample integrity confirmation because of pathologist, clinician or patient concern, six (26.1%) were demonstrated to be discordant, indicating that specimen identification errors or mix-ups had occurred. CONCLUSIONS: Due to their great sensitivity and high discrimination power, forensic identity multiplex systems using either microsatellites or single nucleotide polymorphisms (SNPs) can resolve concerns about pathology specimen identity and integrity.

Relapse in children with acute lymphoblastic leukemia involving selection of a preexisting drug-resistant subclone.

Relapse following remission induction chemotherapy remains a barrier to survival in approximately 20% of children suffering from acute lymphoblastic leukemia (ALL). To investigate the mechanism of relapse, 27 matched diagnosis and relapse ALL samples were analyzed for clonal populations using polymerase chain reaction (PCR)-based detection of multiple antigen receptor gene rearrangements. These clonal markers revealed the emergence of apparently new populations at relapse in 13 patients. More sensitive clone-specific PCR revealed that, in 8 cases, these "relapse clones" were present at diagnosis and a significant relationship existed between presence of the relapse clone at diagnosis and time to first relapse (P < .007). Furthermore, in cases where the relapse clone could be quantified, time to first relapse was dependent on the amount of the relapse clone at diagnosis (r = -0.84; P = .018). This observation, together with demonstrated differential chemosensitivity between subclones at diagnosis, argues against therapy-induced acquired resistance as the mechanism of relapse in the informative patients. Instead these data indicate that relapse in ALL patients may commonly involve selection of a minor intrinsically resistant subclone that is undetectable by routine PCR-based methods. Relapse prediction may be improved with strategies to detect minor potentially resistant subclones early during treatment, hence allowing intensification of therapy.

Early responses to chemotherapy of normal and malignant hematologic cells are prognostic in children with acute lymphoblastic leukemia.

PURPOSE: Improved cure rates for children with acute lymphoblastic leukemia (ALL) have resulted from better relapse prediction, using clinical and laboratory features at diagnosis, and more intensive therapy in high-risk patients. More recently, measurements of the variation in the response of malignant lymphoblasts to chemotherapy in vivo have further improved relapse prediction. It is unknown whether the variation in the response of nonmalignant hematologic cells after chemotherapy correlates with the response of lymphoblasts or risk of relapse. PATIENTS AND METHODS: We retrospectively evaluated myelosuppression during induction and consolidation chemotherapy in 227 children uniformly treated for ALL on consecutive Australian and New Zealand Children's Cancer Study Group protocols. The early response to treatment was assessed in a representative subset (n = 62) by determining minimal residual disease (MRD) level by molecular techniques on the end-of-induction bone marrow sample. RESULTS: We found that a slow rate of myeloid recovery at the end of induction chemotherapy, reflected in a low absolute neutrophil count (ANC), was highly predictive of relapse (P < .0001). Additionally, patients with a high end-of-induction MRD level had a high risk of relapse (P = .001). Multivariate analysis confirmed the independent prognostic significance of MRD and ANC at the end of induction chemotherapy (P < .05). There was no significant association between other measures of myelotoxicity and MRD or relapse. CONCLUSION: We conclude that the responses of normal myeloid cells and malignant lymphoblasts to chemotherapy predict outcome by distinct mechanisms. While these results are promising, their use in the clinical setting needs to be examined in a future randomized controlled trial.

Importance of minimal residual disease testing during the second year of therapy for children with acute lymphoblastic leukemia.

PURPOSE: A high level of minimal residual disease (MRD) after induction chemotherapy in children with acute lymphoblastic leukemia (ALL) is an indicator of relative chemotherapy resistance and a risk factor for relapse. However, the significance of MRD in the second year of therapy is unclear. Moreover, it is unknown whether treatment intervention can alter outcome in patients with detectable MRD. PATIENTS AND METHODS: We assessed the prognostic value of MRD testing in bone marrow samples from 85 children at 1, 12, and 24 months from diagnosis using clone-specific polymerase chain reaction primers designed to detect clonal antigen receptor gene rearrangements. These children were part of a multicenter, randomized clinical trial, which, in the second year of treatment, compared a 2-month reinduction-reintensification followed by maintenance chemotherapy with standard maintenance chemotherapy alone. RESULTS: MRD was detected in 69% of patients at 1 month, 25% at 12 months, and 28% at 24 months from diagnosis. By univariate analysis, high levels of MRD at 1 month, or the presence of any detectable MRD at 12 or 24 months from diagnosis, were highly predictive of relapse. Multivariate analysis showed that MRD testing at 1 and 24 months each had independent prognostic significance. Intensified therapy at 12 months from diagnosis did not improve prognosis in those patients who were MRD positive at 12 months from diagnosis. CONCLUSION: Clinical outcome in childhood ALL can be predicted with high accuracy by combining the results of MRD testing at 1 and 24 months from diagnosis.