Size
In the series by Smoots et al. describing spontaneous tumour regression in 4 (24%) of 17 patients with residual disease (tumour volume ranging from 0.1 to 2.5 cm3), it was concluded that residual tumours with a smaller post-operative volume had a higher chance of regression. Gunny et al. in a series of 83 low- grade CAs, including 13 with incomplete resection, did not find statistically significant independent vari- ables (symptomatology, age, gender, histological grade or the Ki-67 fraction) as predictors of spontaneous regression (Gunny et al.,2005). The numbers involved were too small for meaningful statistical significance of the independent variables, but interestingly tumour
progression did not occur in children with residual tumour volumes below 10 cm3. However, we have personally seen progression occurring in CA tumour residuals with initial volumes lower than 10 cm3, which is in reality a substantial tumour residual volume to begin with.
Hormones
The onset of menarche and rise in female hormones causing tumour regression may be an important fac- tor. There is evidence regarding the protective role of estrogens and other steroid hormones against gliomas, with 1.5 times higher incidence rates of gliomas in men compared to women (Huang et al.,2004; Wigertz et al., 2008), changes in incidence around menarche and menopause (Inskip et al., 1995; McKinley et al., 2000), and presence of hormone receptors in glial tumours (Felini et al., 2009). A case-control study showed decreased incidence amongst women who use hormones during menopause (Huang et al.,2004), and another showed lower risk of gliomas in women that had ever been pregnant compared to never pregnant, with the decreased risk with increasing number of pregnancies (Wigertz et al.,2008).
Use of Dietary Supplements, Natural Remedies and Herbs
Patients and families afflicted with various cancers and tumours often resort to the use of natural foods, herbs and remedies to help their immune system bat- tle with cancer and tumours. There are a myriad of dietary supplements that are said and reported to have beneficial anti-cancer and anti-tumour effects.
Examples include Broccoli, cauliflower and brussles sprouts rich in 3,3-diindolylmethane (DIM) implicated in prostate (Ahmad et al.,2009), breast (Hong et al., 2002) and pancreatic (Abdelrahim et al., 2006) can- cer effects. Garlic is well used for many benefits including its anticancer effects (Ariga and Seki,2006), with some of its constituents being implicated such as Ajoene,Alk(en)yl sulfides, and Gamma-glutamyl-Se- methylselenocysteine (GGMSC). The Chinese herbs containing Camptothecin and hydroxycamptothecin;
harringtonine and homoharringtonine; colchicine and
colchicinamide; curzerenone; monocrotaline; lyco- betaine; oridonin; indirubin; cantharidinare thought to have a positive anti-cancer effect (Hsu, 1980).
However the degree of impact of the myriad possible factors in causing regression of low grade glioamas is almost impossible to ascertain, and maybe it is sim- ply best accepted that diet, lifestyle, environment and psychological factors can all, through the immune sys- tem, exert a variable degree of influence in encouraging tumour regression.
Conclusion
CAs whether treated surgically (residual) or not, are well recognised to undergo regression without con- ventional medical intervention in the form of surgery, radiotherapy and chemotherapy. The frequency of such regression is debated but is estimated to be about 16%.
What is more certain is that such regression seems to occur in small tumour remnants (up to 3.3 cm3) between 3 months and 11–12 years post primary surgi- cal intervention.
The etiology of such regression is likely to be multi factorial and differs from case to case, although there is likely to be influence of multiple mechanisms such as the immune system, cyto-reduction below a critical mass or critical cell type, hormonal influence, apop- tosis, and devascularisation. This regression can even follow initial growth of the surgical remnant as we have observed in cases of PA outside the cerebellum.
Therefore caution should be exercised during surveil- lance of CA surgical remnants, not to rush into further surgery, radiotherapy or chemotherapy.
References
Abdelrahim M, Newman K, Vanderlaag K, Samudio I, Safe S (2006) 3,3-diindolylmethane (DIM) and its derivatives induce apoptosis in pancreatic cancer cells through endo- plasmic reticulum stress-dependent upregulation of DR5.
Carcinogenesis 27:717–728
Abdollahzadeh M, Hoffman HJ, Blazer SI, Becker LE, Humphreys RP, Drake JM, Rutka JT (1994) Benign cere- bellar astrocytoma in childhood: experience at the Hospital for Sick Children 1980–1992. Childs Nerv Syst 10:
380–383
Ahmad A, Kong D, Sarkar SH, Wang Z, Banerjee S, Sarkar FH (2009) Inactivation of uPA and its receptor uPAR by 3,3- diindolylmethane (DIM) leads to the inhibition of prostate cancer cell growth and migration. J Cell Biochem 107:
516–527
Ariga T, Seki T (2006) Antithrombotic and anticancer effects of garlic-derived sulfur compounds: a review. Biofactors 26:
93–103
Balkhoyor KB, Bernstein M (2000) Involution of diencephalic pilocytic astrocytoma after partial resection. Report of two cases in adults. J Neurosurg 93:484–486
Bodey B (2002) Spontaneous regressionof neoplasms: new possibilities for immunotherapy. Expert Opin Biol Ther 2:
459–476
Borit A, Richardson EP Jr (1982) The biological and clinical behaviour of pilocytic astrocytomas of the optic pathways.
Brain 195:167–187
Cairncross JG, Pexman JH, Rathbone MP (1985) Post-surgical contrast enhancement mimicking residual brain tumour. Can J Neurol Sci 12:75
Davis CH, Joglekar VM (1981) Cerebellar astrocytomas in children and young adults. J Neurol Neurosurg Psychiatry 44:820–828
Dirven CM, Mooij JJ, Molenaar WM (1997) Cerebellar pilocytic astrocytoma: a treatment protocol based upon analysis of 73 cases and a review of the literature. Childs Nerv Syst 13:
17–23
Due-Tonnessen BJ, Helseth E, Scheie D, Skullerud K, Aamodt G, Lundar T (2002) Long-term outcome after resection of benign cerebellar astrocytomas in children and young adults (0–19 years): report of 110 consecutive cases. Pediatr Neurosurg 37:71–80
Felini MJ, Olshan AF, Schroeder JC, Carozza SE, Miike R, Rice T, Wrensch M (2009) Reproductive factors and hormone use and risk of adult gliomas. Cancer Causes Control 20:
87–96
Flint D, Fagan P, Panarese A (2005) Conservative management of sporadic unilateral acoustic neuromas. J Laryngol Otol 119:424–428
Gunny RS, Hayward RD, Phipps KP, Harding BN, Saunders DE (2005) Spontaneous regression of residual low-grade cerebellar pilocytic astrocytomas in children. Pediatr Radiol 35:1086–1091
Hercbergs A (1999) Spontaneous remission of cancer—a thy- roid hormone dependent phenomenon? Anticancer Res 19:
4839–4844
Hong C, Firestone GL, Bjeldanes LF (2002) Bcl-2 family- mediated apoptotic effects of 3,3-diindolylmethane (DIM) in human breast cancer cells. Biochem Pharmacol 63:
1085–1097
Hoption Cann SA, van Netten JP, van Netten C, Glover DW (2002) Spontaneous regression: a hidden treasure buried in time. Med Hypotheses 58:115–119
Hsu B (1980) The use of herbs as anticancer agents. Am J Chin Med 8:301–306
Huang K, Whelan EA, Ruder AM, Ward EM, Deddens JA, Davis-King KE, Carreon T, Waters MA, Butler MA, Calvert GM, Schulte PA, Zivkovich Z, Heineman EF, Mandel JS, Morton RF, Reding DJ, Rosenman KD (2004) Reproductive factors and risk of glioma in women. Cancer Epidemiol Biomarkers Prev 13:1583–1588
Inskip PD, Linet MS, Heineman EF (1995) Etiology of brain tumors in adults. Epidemiol Rev 17:382–414
McKinley BP, Michalek AM, Fenstermaker RA, Plunkett RJ (2000) The impact of age and sex on the incidence of glial tumors in New York state from 1976 to 1995. J Neurosurg 93:932–939
Palma L, Celli P, Mariottini A (2004) Long-term follow-up of childhood cerebellar astrocytomas after incomplete resection with particular reference to arrested growth or spontaneo.us tumour regression. Acta Neurochir (Wien) 146:581–588, discussion 588
Papac RJ (1998) Spontaneous regression of cancer: possible mechanisms. In Vivo 12:571–578
Parsa CF, Hoyt CS, Lesser RL, Weinstein JM, Strother CM, Muci-Mendoza R, Ramella M, Manor RS, Fletcher WA, Repka MX, Garrity JA, Ebner RN, Monteiro ML, McFadzean RM, Rubtsova IV, Hoyt WF (2001) Spontaneous regression of optic gliomas: thirteen cases documented by serial neuroimaging. Arch Ophthalmol 119:516–529 Rollins NK, Nisen P, Shapiro KN (1998) The use of early
postoperative MR in detecting residual juvenile cerebellar pilocytic astrocytoma. Am J Neuroradiol 19:151–156 Rossi LN, Triulzi F, Parazzini C, Maninetti MM (1999)
Spontaneous improvement of optic pathway lesions in children with neurofibromatosis type 1. Neuropaediatrics 30:205–209
Rozen WM, Joseph S, Lo PA (2008) Spontaneous regression of low-grade gliomas in pediatric patients without neurofibro- matosis. Pediatr Neurosurg 44:324–328
Saunders DE, Phipps KP, Wade AM, Hayward RD (2005) Surveillance imaging strategies following surgery and/or radiotherapy for childhood cerebellar low-grade astrocy- toma. J Neurosurg 102:172–178
Schmandt SM, Packer RJ, Vezina LG, Jane J (2000) Spontaneous regression of low-grade astrocytomas in child- hood. Pediatr Neurosurg 32:132–136
Singh SK, Clarke ID, Hide T, Dirks PB (2004) Cancer stem cells in nervous system tumors. Oncogene 23:7267–7273 Smoots DW, Geyer JR, Lieberman DM, Berger MS (1998)
Predicting disease progression in childhood cerebellar astro- cytoma. Childs Nerv Syst 14:636–648
Steinbok P (1994) Management and outcome of low-grade astro- cytomas of the midline in children: A retrospective review.
Neurosurgery 35:342–343
Steinbok P, Poskitt K, Hendson G (2006) Spontaneous regres- sion of cerebellar astrocytoma after subtotal resection. Childs Nerv Syst 22:572–576
Takeuchi H, Sato KM, Kubota K, Tattersall M (1997) Chiasmal gliomas with spontaneous regression: proliferation and apop- tosis. Childs Nerv Syst 13:229–233
Wigertz A, Lonn S, Hall P, Auvinen A, Christensen HC, Johansen C, Klaeboe L, Salminen T, Schoemaker MJ, Swerdlow AJ, Tynes T, Feychting M (2008) Reproductive factors and risk of meningioma and glioma. Cancer Epidemiol Biomarkers Prev 17:2663–2670