Effect of photodynamic therapy on recurrent pituitary adenomas: clinical phase I/II trial ‘ an early report

Abstract

Pituitary adenomas, although histologically benign, are not always curable by surgery alone, principally because of dural infiltration, as well as their peculiar anatomical location. Radiotherapy has been employed as an adjuvant therapy to address residual disease with favourable results. This approach is, however, not without side effects, and it cannot be repeated. We are therefore investigating the effectiveness of photodynamic therapy (PDT) on recurrent pituitary adenomas in humans. This study details the protocol applied to 12 patients with recurrent pituitary adenomas, which involved systemic administration of photosensitizer (Photofrin) followed, after a period of 24-48 h, by intraoperative illumination of the tumour bed using 630 nm laser light. The primary end points were visual, endocrine and radiological improvement. The incidence of side effects was also monitored. The longest follow-up is 2 years. Most patients suffering from visual acuity or field defects have shown improvement when followed for 12 months or more. Three patients showed complete recovery of their visual fields. All those who presented with functional adenomas have shown reduction in their hormone levels. Tumour volume, relative to the preoperative size, was 122, 87, 66, 60 and 46% at 4 days, and 3, 6, 18 and 24 months, respectively. One patient developed severe skin photosensitization due to early exposure to direct sunlight and three others displayed minor skin reactions. There was no treatment-related mortality or morbidity. One patient (operated transcranially) developed hemiparesis postoperatively, which recovered completely. We think this is unrelated to the treatment. This prospective study demonstrates that PDT may be safely applied to the pituitary fossa by the trans-sphenoidal route and indicates the need for a randomized, controlled trial in order to establish its therapeutic potential.

Photodynamic therapy of cancer: An update

“…Other brain lesions treated with PDT included malignant ependymomas, 227-228 malignant meningiomas, 229 melanoma and lung cancer brain metastasis, 226,229 and recurrent pituitary adenomas. 230 The initial trails provided encouraging results and the authors concluded that PDT can be used as an adjuvant therapy in brain tumors patients. The photosensitizers employed so far were various formulations of hematoporphyrin derivatives (HPD, Photofrin), ALA as well as mTHPC.…”

Characterization of Perturbing Actions by Verteporfin, a Benzoporphyrin Photosensitizer, on Membrane Ionic Currents

“…These values are quite close to those that are either therapeutically achievable or required for the inhibitory actions on YAP-TEAD complex in different types of neoplastic cells (Faustino et al, 1997; Zhou et al, 2006; Feng et al, 2016; Gibault et al, 2016, 2017; Chen and Hu, 2017). As VP stimulated the I K(Ca) amplitude within a few minutes in GH 3 cells, it is therefore reasonable to elaborate that there is a conceivable link between the anti-neoplastic effects of this compound and its stimulatory actions on I K(Ca) , before it passes through the membrane (Marks et al, 2000).…”

“…Notably, it has been also demonstrated that BK Ca channels are functionally expressed in either retinal pigment epithelial cells, vascular endothelial cells, or amniotic fluid-derived stem cells (Li et al, 2000; Schmidt-Erfurth and Hasan, 2000; Sheu et al, 2005; Hua et al, 2014; Hu et al, 2015; Liu et al, 2015, 2018, 2019a,b). Taking this into account, to what extent VP-induced changes in BK Ca -channel activity existing in these cells are intimately connected with its actions on sensory retina or pituitary adenoma during photodynamic therapy (Marks et al, 2000; Rahimipour et al, 2003; Rosenblatt et al, 2005; Hu et al, 2015; Nemes et al, 2016; Liu et al, 2018; Min et al, 2018; Iacono et al, 2019) remains to be imperatively investigated.…”

“…The photodynamic therapy with different photosensitizers such as hypericin or VP has been previously demonstrated to be effective in the treatment of different types of hyper- or neoplastic tissues, including the residual small tumor in pituitary gland (Faustino et al, 1997; Marks et al, 2000; Valenzeno and Tarr, 2001; DeRosa and Crutchley, 2002; Rahimipour et al, 2003; Brown et al, 2004; Renno et al, 2004; Solban et al, 2006; Triesscheijn et al, 2006; Zhou et al, 2006; Cole et al, 2008; Tekrony et al, 2011; Nemes et al, 2016; Deng et al, 2018). Previous work indeed reported the capability of photosensitizers (e.g., rose bengal) to modify membrane ionic current in pituitary tumor (GH 3 ) cells or heart cells (Tarr et al, 1994; Valenzeno and Tarr, 1998, 2001).…”

The Effect of 5-Aminolevulinic Acid and Its Derivatives on Protoporphyrin IX Accumulation and Apoptotic Cell Death in Castrate-resistant Prostate Cancer Cells

“…The concentration ratios for PPIX and porphyrin analogs such as sapphyrins were as high as 280:1 in malignant xenograft pancreatic tissue versus surrounding skeletal muscle tissue 23 . Extensive studies of 5-ALA and PPIX, as well as novel porphyrin-derived agents, porfimer sodium and temoporfin, show activity in photodynamic therapy for mouse model of ovarian cancer 24 as well as clinical trials on bladder cancer, 14 pituitary tumors, 25 and glioblastoma multiforme. 26 In addition, under certain conditions porphyrins can also act as radiosensitizers.…”