Development of a contouring guide in three different head set-ups for hippocampal sparing radiotherapy: a practical approach.

BACKGROUNDS: Irradiation of the hippocampus plays a role in neurocognitive toxicity. Its delineation is complex and in practice different head position can vary hippocampus morphology on axial images; so atlas in a single standard position can result ineffective to describe different hippocampal morphologies in different head set-up. The purpose of our study was to develop a guide based on magnetic resonance imaging for hippocampus delineation in three different head set-ups. MATERIALS AND METHODS: Three patients were selected to elaborate our guide. Patients were submitted to a planning computed tomography of the brain district in different head positions: 1° patient in neutral, 2° patient in over-extended and 3° patient in head hypo-extended position; axial images of 2-mm thickness were obtained. Computed tomography images were fused with diagnostic brain magnetic resonance images; then hippocampus was delineated according to RTOG atlas. Contours were revised by two neuro-radiologists with >5-year expertise in neuroimaging. RESULTS: A guide was developed for each of three head positions considered. RTOG atlas provided an easy and reliable guide for hippocampus delineation in neutral position of the head. Discrepancies were observed in cranial and caudal limit in case of head over/hypo-extension, as well as in hippocampal morphology near the encephalic trunk where hippocampus takes an oblong shape in over-extended set-up, and short and stocky in hypo-extension. CONCLUSION: Our guide can represent a useful tool for hippocampal delineation in clinical practice and for different anatomic variations due to different head positions. Certainly, it should be validated in practice.

Advances in Lipidomics for Cancer Biomarkers Discovery.

Lipids play critical functions in cellular survival, proliferation, interaction and death, since they are involved in chemical-energy storage, cellular signaling, cell membranes, and cell-cell interactions. These cellular processes are strongly related to carcinogenesis pathways, particularly to transformation, progression, and metastasis, suggesting the bioactive lipids are mediators of a number of oncogenic processes. The current review gives a synopsis of a lipidomic approach in tumor characterization; we provide an overview on potential lipid biomarkers in the oncology field and on the principal lipidomic methodologies applied. The novel lipidomic biomarkers are reviewed in an effort to underline their role in diagnosis, in prognostic characterization and in prediction of therapeutic outcomes. A lipidomic investigation through mass spectrometry highlights new insights on molecular mechanisms underlying cancer disease. This new understanding will promote clinical applications in drug discovery and personalized therapy.

Early percutaneous endoscopic gastrostomy and nutritional supplementation for patients with head and neck cancer: an Italian survey of head and neck radiation oncologists.

PURPOSE: The aim of this paper is to survey among Italian radiation oncologists about the role of nutritional supplementation and an early placement of endoscopic percutaneous gastrostomy in head and neck cancer patients treated with radiotherapy or chemo-radiotherapy. METHODS: The survey was carried out in 106 Italian centers of radiation oncology through a SurveyMonkey online interface questionnaire. RESULTS: The response rate to the survey was of 63%, with 67 analyzable questionnaires. The majority of the respondents do not use preventive nutritional supplement. In 73.1% of the cases, percutaneous endoscopic gastrostomy (PEG) is positioned only in case of necessity. The 82.1% of the interviewed physicians, indeed, argued that the preventive placement of the endoscopic percutaneous gastrostomy should not be a standard procedure. Nutritional counseling before starting a treatment is not a routine, but 88.1% of the respondents stated that this should represent a standard procedure. CONCLUSIONS: Although some studies agree that a reactive approach should be preferred to an early endoscopic percutaneous gastrostomy placement, firm evidences and a clear consensus are still lacking. This survey shows a wide agreement about both timing and criteria for endoscopic percutaneous gastrostomy placement; however, the management of nutritional supplementation in head and neck cancer patients appears to be still widely variable and to deserve more focused studies.

Delineating brachial plexus, cochlea, pharyngeal constrictor muscles and optic chiasm in head and neck radiotherapy: a CT-based model atlas.

BACKGROUND AND PURPOSE: Sparing of the organs at risk is one of the primary end-points of radiotherapy. The effects of organ-at-risk delineation on the dosimetric parameters can be critical and can influence treatment planning and outcomes. The aim of our study was to provide anatomical boundaries for the identification and delineation of the following critical organs at risk in the head and neck district: brachial plexus, cochlea, pharyngeal constrictor muscles and optic chiasm. PATIENTS AND METHODS: One patient was initially selected to elaborate our atlas. This patient was subjected to a planning computed tomography of the brain and head and neck district; axial images of 3-mm thickness at 3-mm intervals were obtained. In the same set-up a magnetic resonance imaging study was also performed. The obtained images were fused based on anatomical landmarks and used by a radiation oncologist, supported by a neuroradiologist, to provide anatomo-radiological limits for the identification of the brachial plexus, cochlea, pharyngeal constrictor muscles and optic chiasm. These limits were further verified on three consecutive patients. RESULTS: A computed tomography-based atlas was developed with definition of cranial, caudal, medial, lateral, anterior and posterior limits for each organ considered. CONCLUSIONS: This study allows improvement of definitions of anatomic boundaries for the brachial plexus, cochlea, pharyngeal constrictor muscles and optic chiasm. Our multidisciplinary experience led to the production of an institutional reference tool that could represent a useful aid for radiation oncologists in clinical practice.

Treatment Intensification for Locally Advanced Rectal Cancer: Impact on Pathological Complete Response and Outcomes.

AIM: Pathological complete response (pCR) and clinical outcomes [overall survival (OS), disease-free survival (DFS), locoregional control (LC)] were evaluated in a single-institution experience of different schedules of neoadjuvant chemoradiotherapy (CRT) for patients with locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Data for 322 patients with LARC were retrospectively analyzed. pCR was evaluated according to Mandard tumor regression grade (TRG). The Kaplan-Meier method was used to estimate OS, DFS and LC. RESULTS: Three hundred and three (94.1%) patients underwent surgery. pCR was observed in 81 patients (26.7%), with TRG1-2 rate of 41.8%. The 5- and 10-year OS, DFS and LC rates were 82.5%±2.5% and 65.5%±3.8%, 81.2%±2.4% and 79.3%±2.9%, 93.1%±1.7% and 90.5%±2.1%, respectively. CONCLUSION: Neoadjuvant CRT in LARC patients resulted in favorable long-term oncological outcomes, with a high pCR rate and acceptable toxicity.

Assessment of bowel and anal sphincter function after neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

PURPOSE: To report long-term effects on anorectal function and bowel disorders and late toxicity rate of preoperative chemoradiotherapy in patients with locally advanced rectal cancer. METHODS: Between 2000 and 2016, 201 patients treated with different neoadjuvant schedules of chemotherapy and radiotherapy doses were retrospectively analyzed. The Memorial Sloan-Kettering Cancer Center score was used for the evaluation of anal sphincter function. RESULTS: The median follow-up time was 68 months (interquartile range 35-113 months). Radical resection was performed in 188 (93.5%) patients with a pathologic complete response rate of 26.4%. Overall sphincter function resulted excellent in 105 (52.2%) patients, good in 13 (6.5%), fair in 10 (5.0%), and poor (incontinence) in 40 (19.9%), with a persistent stoma rate of 16.4%. A further evaluation on 194 patients showed an improvement of sphincter function after 2 years in 11.9% of them. Seventy-three patients presenting stoma or poor sphincter function were re-evaluated for quality of life (QoL) indexes. Twenty-one (29%), 19 (26%), and 24 (33%) of them declared some variations concerning well-being, fatigue, and ability to perform daily activities. The 5-year overall survival, disease-free survival, and local recurrence rates were 88.0% ± 2.6%, 86.3% ± 2.5%, and 94.6% ± 1.9%, respectively. CONCLUSIONS: In our study, neoadjuvant chemoradiotherapy was associated with good results in terms of sphincter function, late toxicities, and QoL indexes. A routine use of assessment scales could contribute to a better selection of patients with increased risk of developing functional disorders who could benefit from neoadjuvant therapy.

A Feasibility Study for in vivo Dosimetry Procedure in Routine Clinical Practice.

PURPOSE: The aim of the in vivo dosimetry, during the fractionated radiation therapy, is the verification of the correct dose delivery to patient. Nowadays, in vivo dosimetry procedures for photon beams are based on the use of the electronic portal imaging device and dedicated software to elaborate electronic portal imaging device images. METHODS: In total, 8474 in vivo dosimetry tests were carried out for 386 patients treated with 3-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and volumetric modulated arc therapy techniques, using the SOFTDISO. SOFTDISO is a dedicated software that uses electronic portal imaging device images in order to (1) calculate the R index, that is, the ratio between daily reconstructed dose and the planned one at isocenter and (2) perform a γ-like analysis between the signals, S, of a reference electronic portal imaging device image and that obtained in a daily fraction. It supplies 2 indexes, the percentage γ% of points with γ < 1 and the mean γ value, γmean. In γ-like analysis, the pass criteria for the signals agreement ΔS% and distance to agreement Δd have been selected based on the clinical experience and technology used. The adopted tolerance levels for the 3 indexes were fixed in 0.95 ≤ R ≤ 1.05, γ% ≥ 90%, and γmean ≤ 0.5. RESULTS: The results of R ratio, γ-like, and a visual inspection of these data reported on a monitor screen permitted to individuate 2 classes of errors (1) class 1 that included errors due to inadequate standard quality controls and (2) class 2, due to patient morphological changes. Depending on the technique and anatomical site, a maximum of 18% of tests had at least 1 index out of tolerance; once removed the causes of class-1 errors, almost all patients (except patients with 4 lung and 2 breast cancer treated with 3-dimensional conformal radiotherapy) presented mean indexes values ([Formula: see text], [Formula: see text]%, and [Formula: see text] ) within tolerance at the end of treatment course. Class-2 errors were found in some patients. CONCLUSIONS: The in vivo dosimetry procedure with SOFTDISO resulted easily implementable, able to individuate errors with a limited workload.

Serum lipidomic study reveals potential early biomarkers for predicting response to chemoradiation therapy in advanced rectal cancer: A pilot study.

PURPOSE: Prospective detection of patients with advanced rectal cancer (LARC) who have a higher probability of responding to preoperative chemoradiotherapy (CRT) may provide individualized therapy. Lipidomics is an emerging science dedicated to the characterization of lipid fingerprint involved in different pato-physiological conditions. The purpose of this study is to highlight a typical lipid signature able to predict the tumor response to CRT. EXPERIMENTAL DESIGN: A prospective global analysis of lipids in 54 sera from 18 LARC patients treated with preoperative CRT was performed. Samples were collected at 3 time points: before (T0), at 14th day and at 28th day of CRT. An open LC-MS/MS analysis was performed to characterize lipid expression at T0. Differential lipids were validated by an independent approach and studied during treatment. RESULTS: From 65 differential lipids highlighted between responder (RP) vs not responder (NRP) patients, five lipids were validated to predict response at T0: SM(d18:2/18:1), LysoPC (16:0/0:0), LysoPC (15:1(9z)/0:0), Lyso PE (22:5/0:0) and m/z= 842.90 corresponding to a PC containing 2 fatty acids of 40 carbons totally. The levels of these lipids were lower in NRP before treatment. The ROC curve obtained by combining these five lipid signals showed an AUC of 0.95, evidence of good sensitivity and specificity in discriminating groups. CONCLUSION: Our results are in agreement with previous evidences about the role of lipids in determining the tumor response to therapy and suggest that the study of serum lipid could represent a useful tool in prediction of CRT response and in personalizing treatment.

Outcomes in Patients with pT1-T2, pN0-N1 Breast Cancer After Conservative Surgery and Whole-breast Radiotherapy.

AIM: To evaluate locoregional recurrence, overall survival, disease-free survival and prognostic influence of the number of positive lymph nodes and other variables in breast cancer treatment. PATIENTS AND METHODS: A total of 377 patients with pT1-T2, pN0-N1 invasive breast carcinoma treated from 2005 to 2013 were retrospectively evaluated. Patients underwent conservative surgery followed by whole-breast radiotherapy. Clavicular region irradiation was not performed. RESULTS: With a median follow-up of 4 years, locoregional recurrence rate was 3.4% (nodal recurrence=1.06%). Expression of progesterone receptors was significantly associated with better disease-free survival, tumor size (T>2 cm) with poorer disease-free survival, locoregional recurrence and poorer overall survival; the presence of three nodal metastases was related to significantly poorer overall survival (p=0.024). CONCLUSION: Whole-breast adjuvant radiotherapy without nodal irradiation after breast-conserving surgery led to low rate of locoregional recurrence and high rates of overall survival and disease-free survival in patients with pT1-T2 pN0-N1 breast cancer.