Luigi Pirtoli

Texture analysis as a predictor of radiation-induced xerostomia in head and neck patients undergoing IMRT

PurposeImage texture analysis (TA) is a heterogeneity quantifying approach that cannot be appreciated by the naked eye, and early evidence suggests that TA has great potential in the field of oncology. The aim of this study is to evaluate parotid gland texture analysis (TA) combined with formal dosimetry as a factor for predicting severe late xerostomia in patients undergoing radiation therapy for head and neck cancers.MethodsWe performed a retrospective analysis of patients treated at our Radiation Oncology Unit between January 2010 and December 2015, and selected the patients whose normal dose constraints for the parotid gland (mean dosexa0<xa026xa0Gy for the bilateral gland) could not be satisfied due to the presence of positive nodes close to the parotid glands. The parotid gland that showed the higher V30 was contoured on CT simulation and analysed with LifeX Software©. TA parameters included features of grey-level co-occurrence matrix (GLCM), neighbourhood grey-level dependence matrix (NGLDM), grey-level run length matrix (GLRLM), grey-level zone length matrix (GLZLM), sphericity, and indices from the grey-level histogram. We performed a univariate and multivariate analysis between all the texture parameters, the volume of the gland, the normal dose parameters (V30 and Mean Dose), and the development of severe chronic xerostomia.ResultsSeventy-eight patients were included and 25 (31%) developed chronic xerostomia. The TA parameters correlated with severe chronic xerostomia included V30 (OR 5.63), Dmean (OR 5.71), Kurtosis (OR 0.78), GLCM Correlation (OR 1.34), and RLNU (OR 2.12). The multivariate logistic regression showed a significant correlation between V30 (0.001), GLCM correlation (p: 0.026), RLNU (p: 0.011), and chronic xerostomia (pxa0<xa00.001, R2:0.664).ConclusionsXerostomia represents an important cause of morbidity for head and neck cancer survivors after radiation therapy, and in certain cases normal dose constraints cannot be satisfied. Our results seem promising as texture analysis could enhance the normal dose constraints for the prediction of xerostomia.

Persistent hiccup after chemo-radiotherapy in nasopharyngeal cancer: an atypical side effect?

Nasopharyngeal carcinoma (NPC) is a relatively uncommon cancer of the head and neck region, although it has a higher incidence in certain populations, including Southern Asian and Chinese [1]. The most common histological type of NPC is the undifferentiated nonkeratinizing histotype, strongly associated with the Epstein–Barr virus (EBV) in almost all of the cases, whereas the keratinizing and the basaloid histotypes are less common. The symptomatology includes nasal symptoms, otitis, local pain, headache and cranial nerve involvement, and this varied spectrum often results in delayed diagnosis. Chemotherapy plus radiotherapy in different associations is generally accepted as the first-line therapy, although acute and late toxicities remain highly detrimental [2]. Intensity-modulated radiation therapy can highly concentrate the radiation dose to target volumes while avoiding or reducing radiation doses to normal tissues and organs, thereby leading to gains in the therapeutic ratio in an anatomically complex site such as the nasopharynx. Our patient was a 45-year-old italian male with a nonkeratinizing NPC, clinical staging cT3N2M0, receiving two cycles of induction chemotherapy with cisplatin (75 mg/m), docetaxel (75 mg/m) and 5-fluorouracil (750 mg/m 9 5 days) every 4 weeks. The induction chemotherapy was well tolerated with a partial response (50 % reduction on CT scan) and the only side effects were alopecia (grade I), diarrhea (grade I) and weakness (grade I). The patient was then submitted to radiation therapy with concomitant chemotherapy (cisplatinum 40 mg/m/ weekly) and the total radiation therapy dose was 6600 cGy to planned target volume 1 (PTV1), including nasopharynx, positive-neck node levels II and III bilaterally, with a fractionation of 220 cGy per fraction, 6000 cGy to PTV2 (skull base, neck node levels Ib and V, both sides), with a fractionation of 200 cGy per fraction, and 5400 cGy to PTV3 (neck node levels IV, both sides), fractionation 180 cGy per fraction. Total dose, fractionation and contouring of target volumes and organs at risk were according to the recent literature [3]. Treatment side effects were characterized by thrombocytopenia (grade III), leukopenia (grade II), lingual edema (grade I), mucositis (grade III), epistaxis (grade I), rise in transaminases (grade II) and otitis (grade I), but, 3 weeks after the end of the chemoradiation treatment, our patient developed nausea, unresponsive to usual antiemetics, and, few days later pernicious hyperemesis and severe hiccup. Brain MRI and neurological examination were negative, thus suspecting an isolated irritation of the nucleus of the vagal nerve we started chlorpromazine endovenous (100 mg/die), with clinical improvement in 3 days. & Valerio Nardone v.nardone@hotmail.it

Automatic segmentation of glioblastoma for radiation therapy treatment planning

During the radiation therapy (RT) process, the treatment is planned and simulated with a treatment planning system (TPS): the organs at risk (OAR) and the tumor target are identified and contoured, and the RT dose, delivered by the planned photon beams, is obtained for optimization of the resulting plan. The contouring work-up of tumor target identifies the Planning Treatment Volume (PTV), i.e. the physical RT treatment volume. PTV of glioblastomas (GB) includes, after expansion, Gross Tumor Volume (GTV, the tumor) and Clinical Target Volume (CTV, tumor plus edema). Usually, GTV contouring is performed manually. In this work, we used GlioCAD, a Computer-Assisted Detection software for automatic contouring of gliomas in MRI/DTI, to delineate GTV. The dataset included the images of 21 patients undergoing RT for GB. For each patient, we co-registered CT-planning images and diagnostic MRI (16 T1-gad, 6 T2 Flair, 13 Flair Fat Sat), which were used for GlioCAD training and validation. CAD outlined the tumor with good accuracy, after ruling out some false positives in post-processing. We identified GTVs, suitable for RT requirements. An evolution of GlioCAD will take into account edema for outlining CTV. The method seems promising. A further automatic system for the delineation of sites at risk in the brain is under development, which may be helpful for standardization of RT-treatment planning.

Autophagy in Human Brain Cancer: Therapeutic Implications

Autophagy is a physiological process, evolutionarily conserved, able to preserve cells from both endogenous and environmental threats. Baseline autophagy contributes to the maintenance of cellular homeostasis, and autophagic flow is upregulated in response to many adverse conditions, including nutrient or growth factor deprivation, accumulation of unfolded proteins, and intracellular infection. Although autophagy frequently exerts cytoprotective functions by acting as a stress response mechanism, in some settings, it may contribute to the execution of cell death, representing the type 2 programmed cell death. Moreover, autophagy drives key processes in cancer, including glioblastoma (the most frequent and malignant brain tumor in adults). An effective autophagy function may protect cells against the consequences of gene mutation and altered signal pathways leading to tumor initiation, promotion, and progression toward highly aggressive behaviors, such as enhanced proliferation, infiltration, and metastases. Moreover, autophagy activation has been extensively reported as able to modulate effectiveness of current anticancer agents, such as chemotherapy, ionizing radiation, target therapy, and immunotherapy. However, its role as a prosurvival or prodeath cellular process is still debated. In this chapter, emerging results from scientific literature are reported, describing in vitro, in vivo, and preclinical evidence of autophagy involvement in glioblastoma. The chapter also describes how the autophagy process can switch to apoptosis (type 1 programmed cell death) or how it can be modulated by microRNA (small noncoding RNA molecules that regulate protein expression by cleaving or repressing the translation of target mRNAs). In conclusion, the autophagy process plays a crucial role not only in tumor development, progression, and malignancy, but also in modulating the current therapy, providing new encouraging strategies for tumor treatment.

Autophagy in Human Brain Cancer

Autophagy is a physiological process, evolutionarily conserved, able to preserve cells from both endogenous and environmental threats. Baseline autophagy contributes to the maintenance of cellular homeostasis, and autophagic flow is upregulated in response to many adverse conditions, including nutrient or growth factor deprivation, accumulation of unfolded proteins, and intracellular infection. Although autophagy frequently exerts cytoprotective functions by acting as a stress response mechanism, in some settings, it may contribute to the execution of cell death, representing the type 2 programmed cell death. Moreover, autophagy drives key processes in cancer, including glioblastoma (the most frequent and malignant brain tumor in adults). An effective autophagy function may protect cells against the consequences of gene mutation and altered signal pathways leading to tumor initiation, promotion, and progression toward highly aggressive behaviors, such as enhanced proliferation, infiltration, and metastases. Moreover, autophagy activation has been extensively reported as able to modulate effectiveness of current anticancer agents, such as chemotherapy, ionizing radiation, target therapy, and immunotherapy. However, its role as a prosurvival or prodeath cellular process is still debated. In this chapter, emerging results from scientific literature are reported, describing in vitro, in vivo, and preclinical evidence of autophagy involvement in glioblastoma. The chapter also describes how the autophagy process can switch to apoptosis (type 1 programmed cell death) or how it can be modulated by microRNA (small noncoding RNA molecules that regulate protein expression by cleaving or repressing the translation of target mRNAs). In conclusion, the autophagy process plays a crucial role not only in tumor development, progression, and malignancy, but also in modulating the current therapy, providing new encouraging strategies for tumor treatment.

Chapter 6 – Autophagy in Human Brain Cancer: Therapeutic Implications

Autophagy is a physiological process, evolutionarily conserved, able to preserve cells from both endogenous and environmental threats. Baseline autophagy contributes to the maintenance of cellular homeostasis, and autophagic flow is upregulated in response to many adverse conditions, including nutrient or growth factor deprivation, accumulation of unfolded proteins, and intracellular infection. Although autophagy frequently exerts cytoprotective functions by acting as a stress response mechanism, in some settings, it may contribute to the execution of cell death, representing the type 2 programmed cell death. Moreover, autophagy drives key processes in cancer, including glioblastoma (the most frequent and malignant brain tumor in adults). An effective autophagy function may protect cells against the consequences of gene mutation and altered signal pathways leading to tumor initiation, promotion, and progression toward highly aggressive behaviors, such as enhanced proliferation, infiltration, and metastases. Moreover, autophagy activation has been extensively reported as able to modulate effectiveness of current anticancer agents, such as chemotherapy, ionizing radiation, target therapy, and immunotherapy. However, its role as a prosurvival or prodeath cellular process is still debated. In this chapter, emerging results from scientific literature are reported, describing in vitro, in vivo, and preclinical evidence of autophagy involvement in glioblastoma. The chapter also describes how the autophagy process can switch to apoptosis (type 1 programmed cell death) or how it can be modulated by microRNA (small noncoding RNA molecules that regulate protein expression by cleaving or repressing the translation of target mRNAs). In conclusion, the autophagy process plays a crucial role not only in tumor development, progression, and malignancy, but also in modulating the current therapy, providing new encouraging strategies for tumor treatment.