12 maart 2011: Bron: Medscape en J Clin Oncol. 2010 May 1;28(13):2293-9. Epub 2010 Apr 5.

Een nieuwe studie toont opnieuw aan dat gemeten progressie tijdens gebruik van Temodal bij hersentumoren in 20% tot 40% van de gevallen een pseudoprogressie is. We berichtten daar al eerder over maar nu wordt ook uitgelegd in een artikel van Medscape hoe dat komt en hoe is uit te zoeken of er sprake is van een werkelijke progressie of een pseudoprogressie. Hier enkele citaten uit artikel van Medscape en daaronder abstract van studie hoe pseudoprogressie te onderscheiden van werkelijke progressie en daar weer onder eerder gepubliceerde studies over dit onderwerp.

Citaat uit artikel van Medscape: .......Pseudoprogression and pseudoresponse have made conventional imaging with gadolinium-based contrast agents almost obsolete. There is a need for methods that use biomarkers, which would allow radiologists to differentiate a pseudophenomenon from real progression or response, noted presenter Meng Law, MD, FRACR, professor of radiology and neurological surgery, director of neuroradiology, Keck School of Medicine, University of Southern California–Los Angeles, who presented his work.

According to Dr. Law, pseudoprogression is found in 20% to 40% of patients with glioblastoma treated with temozolomide. "This can explain about half of all cases of increasing lesions and enhancement during and after treatment. The key is to differentiate between true progression and pseudoprogression. It is very difficult to know what sort of treatment triage should occur in these patients. Should we continue therapy, stop therapy, or carry out surgery?" Dr. Law asked.

In one study, patients with pseudoprogression demonstrated a consistent pattern of low permeability on the signal-intensity curve and permeability maps and low cerebral blood volume (<1.75). Magnetic resonance spectroscopy demonstrated an increase in Cho/Cho(n) and an increase in lipid and lactate. In patients with pseudoprogression, these results appeared in the first 2 to 6 months of treatment, and the tumors usually regressed 6 to 12 months after the commencement of temozolomide and radiation therapy.

"In true disease progression, there is elevated perfusion or increased vascularity, as well as damage to the blood–brain barrier. This makes sense biologically, but in pseudoprogression, there is no elevation in perfusion, just damage to the blood–brain barrier caused by temozolomide. There's no increased vascularity," Dr. Law explained. Lees verder het artikel van Medscape

J Clin Oncol. 2010 May 1;28(13):2293-9. Epub 2010 Apr 5.

Parametric response map as an imaging biomarker to distinguish progression from pseudoprogression in high-grade glioma.

Tsien C, Galbán CJ, Chenevert TL, Johnson TD, Hamstra DA, Sundgren PC, Junck L, Meyer CR, Rehemtulla A, Lawrence T, Ross BD.

Department of Radiation Oncology, University of Michigan Medical Center, 1500 E. Medical Center Dr, Ann Arbor, MI 48109, USA. ctsien@umich.edu

Comment in:

Abstract

PURPOSE: To assess whether a new method of quantifying therapy-associated hemodynamic alterations may help to distinguish pseudoprogression from true progression in patients with high-grade glioma.

PATIENTS AND METHODS: Patients with high-grade glioma received concurrent chemoradiotherapy. Relative cerebral blood volume (rCBV) and blood flow (rCBF) maps were acquired before chemoradiotherapy and at week 3 during treatment on a prospective institutional review board-approved study. Pseudoprogression was defined as imaging changes 1 to 3 months after chemoradiotherapy that mimic tumor progression but stabilized or improved without change in treatment or for which resection revealed radiation effects only. Clinical and conventional magnetic resonance (MR) parameters, including average percent change of rCBV and CBF, were evaluated as potential predictors of pseudoprogression. Parametric response map (PRM), an innovative, voxel-by-voxel method of image analysis, was also performed.

RESULTS: Median radiation dose was 72 Gy (range, 60 to 78 Gy). Of 27 patients, stable disease/partial response was noted in 13 patients and apparent progression was noted in 14 patients. Adjuvant temozolomide was continued in all patients. Pseudoprogression occurred in six patients. Based on PRM analysis, a significantly reduced blood volume (PRM(rCBV)) at week 3 was noted in patients with progressive disease as compared with those with pseudoprogression (P < .01). In contrast, change in average percent rCBV or rCBF, MR tumor volume changes, age, extent of resection, and Radiation Therapy Oncology Group recursive partitioning analysis classification did not distinguish progression from pseudoprogression.

CONCLUSION: PRM(rCBV) at week 3 during chemoradiotherapy is a potential early imaging biomarker of response that may be helpful in distinguishing pseudoprogression from true progression in patients with high-grade glioma.

PMID: 20368564 [PubMed - indexed for MEDLINE]PMCID: PMC2860441 [Available on 2011/5/1]

9 januari 2011: Bron: The Canadian Journal of Neurological Sciences

Bij ca. 30% van de mensen met een hersentumor Glioblastoom Muiltiforme die naast bestraling de chemo temodal krijgen voorgeschreven ontstaat er progressie binnen een half jaar. Echter bij een derde van die mensen is hier sprake van pseudo progressie, dus progressie op een scan die geen progrssie van de kanker is, maar bv. veroorzaakt door effecten van de bestraling. Het advies nu is dat niet gestopt moet worden met Temodal omdat bij de patienten waarbij gewoon door werd gegaan met temodal de mediane levensduur significant werd verlengd. Dit blijkt uit een Canadese studie met 111 patienten met een hersentumor. De mediane overlevingstijd voor de hele groep bleek 56,7 weken. De mediane levensduur voor de mensen waarbij een pseudo progressie werd vastgesteld bleek 124.9 weken versus 36.0 weken, p=0.0286 . Hieronder het abstract en daaronder een eerder artikel over pseudoprogressie uit 2009. Het volledige recente studierapport kunt u lezen in PDF file als u hier klikt.

The Canadian Journal of Neurological Sciences
	Issue:	Volume 37, Number 1 / January 2010
	Pages:	36 - 42
	URL:	Linking Options

Pseudoprogression Following Chemoradiotherapy for Glioblastoma Multiforme

Paul Sanghera ^{A1 A2 A6 A7}, James Perry ^{A1 A3 A6}, Arjun Sahgal ^{A1 A2 A6}, Sean Symons ^{A4 A6}, Richard Aviv ^{A1 A6}, Meredith Morrison ^{A1 A6}, Kelvin Lam ^A5, Phillip Davey ^{A1 A2 A6}, May N. Tsao ^{A1 A2 A6}

^A1 Odette Cancer Centre
^A2 Department of Radiation Oncology, University of Toronto
^A3 Division of Neurology, Department of Medicine, University of Toronto
^A4 Department of Medical Imaging, University of Toronto
^A5 Institute for Clinical Evaluative Sciences, University of Toronto
^A6 Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
^A7 University Hospital Birmingham, Edgbaston, Birmingham, United Kingdom

Abstract:

Purpose: Pseudoprogression (psPD) is now recognised following radiotherapy with concurrent temozolomide (RT/TMZ) for glioblastoma multiforme (GBM). The aim of this study was to determine the incidence of psPD following RT/TMZ and the effect of psPD on prognosis.
Materials/Methods: All patients receiving RT/TMZ for newly diagnosed GBM were identified from a prospective database. Clinical and radiographic data were retrospectively reviewed. Early progression was defined as radiological progression (RECIST criteria) during or within eight weeks of completing RT/TMZ. Pseudoprogression was defined as early progression with subsequent disease stabilization, without salvage therapy, for at least six months from completion of RT/TMZ. The primary outcome was overall survival (Kaplan-Meier) and log rank analysis was used to compare groups.
Results: Out of 111 patients analyzed, 104 were evaluable for radiological response. Median age was 58 years and median follow-up 55 weeks. Early progression was confirmed in 26% and within this group 32% had psPD. Median survival for the whole cohort was 56.7 weeks [95% CI (51.0, 71.3)]. Median survival for patients with psPD was significantly higher than for patients with true early progression (124.9 weeks versus 36.0 weeks, p=0.0286).
Conclusions: Approximately one third of patients with early progression were found to have psPD which was associated with a favourable prognosis. Maintenance TMZ should not be abandoned on the basis of seemingly discouraging imaging features identified within the first three months after RT/TMZ.

18 oktober 2009: Bron: Can J Neurol Sci. 2009 Sep;36(5):617-22.

Chemo - Temozolomide - Temodal bij hersentumoren - Glioblastomen Multiforme geeft soms op scans een pseudo progressie te zien. Dit blijkt uit een retropostpectieve studie bij 43 evalueerbare patienten. Het bleek dat 25 patienten (58%) een progressie lieten zien bij een scan na de toediening van Temozolomide - Temodal. Bij 20 van de 25 patienten werd gewoon doorgegaan met de Temodal en bleek de mediane overlevingsduur aanmerkelijk beter voor de patienten (14,5 maanden t.o. 9,1 maanden) waarbij die zogenaamde pseudoprogressie was opgetreden tegenover degenen die echte progressie hadden getoond op een scan. .Hier de letterljke vertaling van de studie. Daaronder het originele abstract

Resultaten: Van de 43 evalueerbare patiënten, toonden 25 (58%) radiografische progressie op de eerste MRI na gelijktijdige behandeling. Twintig van deze patienten gingen door met adjuvante TMZ. (dus bleven Temodal krijgen) , en een daaropvolgend onderzoek toonde aan dat er sprake was van radiografische pseudoprogression in 10 gevallen (50%). Mediane overleving (MS) was beter bij patiënten met pseudoprogression (MS 14,5 maanden) in vergelijking met degenen met echte radiologische progressie (MS 9,1 maanden, p = 0,025) hadden getoond. De MS patiënten met pseudoprogression was vergelijkbaar met de pateienten die met stabiele ziekte reageerden tijdens gelijktijdige behandeling (p = 0,31). Noch de omvang van de oorspronkelijke resectie noch de dosering dexamethason was geassocieerd met pseudoprogression.

Can J Neurol Sci. 2009 Sep;36(5):617-22.
Population-based study of pseudoprogression after chemoradiotherapy in GBM.

Roldán GB, Scott JN, McIntyre JB, Dharmawardene M, de Robles PA, Magliocco AM, Yan ES, Parney IF, Forsyth PA, Cairncross JG, Hamilton MG, Easaw JC.

Department of Oncology, Tom Baker Cancer Centre, Alberta Cancer Board, Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.

INTRODUCTION: Chemoradiotherapy followed by monthly temozolomide (TMZ) is the standard of care for patients with glioblastoma multiforme (GBM). Case reports have identified GBM patients who experienced transient radiological deterioration after concurrent chemoradiotherapy which stabilized or resolved after additional cycles of adjuvant TMZ, a phenomenon known as radiographic pseudoprogression. Little is known about the natural history of radiographic pseudoprogression.

METHODS: We retrospectively evaluated the incidence of radiographic pseudoprogression in a population-based cohort of GBM patients and determined its relationship with outcome and MGMT promoter methylation status.

RESULTS: Out of 43 evaluable patients, 25 (58%) exhibited radiographic progression on the first MRI after concurrent treatment. Twenty of these went on to receive adjuvant TMZ, and subsequent investigation demonstrated radiographic pseudoprogression in 10 cases (50%). Median survival (MS) was better in patients with pseudoprogression (MS 14.5 months) compared to those with true radiologic progression (MS 9.1 months, p=0.025). The MS of patients with pseudoprogression was similar to those who stabilized/responded during concurrent treatment (p=0.31). Neither the extent of the initial resection nor dexamethasone dosing was associated with pseudoprogression.

CONCLUSIONS: These data suggest that physicians should continue adjuvant TMZ in GBM patients when early MRI scans show evidence of progression following concurrent chemoradiotherapy, as up to 50% of these patients will experience radiologic stability or improvement in subsequent treatment cycles.

biomarkers, pseudo progressie, glioblastoom, hersentumoren, temodal