Multi-omics staging of locally advanced rectal cancer predicts treatment response: a pilot study.

Treatment response assessment of rectal cancer patients is a critical component of personalized cancer care and it allows to identify suitable candidates for organ-preserving strategies. This pilot study employed a novel multi-omics approach combining MRI-based radiomic features and untargeted metabolomics to infer treatment response at staging. The metabolic signature highlighted how tumor cell viability is predictively down-regulated, while the response to oxidative stress was up-regulated in responder patients, showing significantly reduced oxoproline values at baseline compared to non-responder patients (p-value < 10-4). Tumors with a high degree of texture homogeneity, as assessed by radiomics, were more likely to achieve a major pathological response (p-value < 10-3). A machine learning classifier was implemented to summarize the multi-omics information and discriminate responders and non-responders. Combining all available radiomic and metabolomic features, the classifier delivered an AUC of 0.864 (± 0.083, p-value < 10-3) with a best-point sensitivity of 90.9% and a specificity of 81.8%. Our results suggest that a multi-omics approach, integrating radiomics and metabolomic data, can enhance the predictive value of standard MRI and could help to avoid unnecessary surgical treatments and their associated long-term complications.

Pattern of care for re-irradiation in locally recurrent rectal cancer: a national survey on behalf of the AIRO gastrointestinal tumors study group.

PURPOSE: Radical resection (R0) represents the best curative treatment for local recurrence (LR) rectal cancer. Re-irradiation (re-RT) can increase the rate of R0 resection. Currently, there is a lack of guidelines on Re-RT for LR rectal cancer. The Italian Association of Radiation and clinical oncology for gastrointestinal tumors (AIRO-GI) study group released a national survey to investigate the current clinical practice of external beam radiation therapy in these patients. MATERIAL AND METHODS: In February 2021, the survey was designed and distributed to members of the GI working group. The questionnaire consisted of 40 questions regarding center characteristics, clinical indications, doses, and treatment techniques of re-RT for LR rectal cancer. RESULTS: A total of 37 questionnaires were collected. Re-RT was reported as an option for neoadjuvant treatment in resectable and unresectable disease by 55% and 75% of respondents, respectively. Long-course treatment with 30-40 Gy (1.8-2 Gy/die, 1.2 Gy bid) and hypofractionated regimen of 30-35 Gy in 5 fractions were used in most centers. A total dose of 90-100 Gy as EqD2 dose (α/ß = 5 Gy) was delivered by 46% of the respondents considering the previous treatment. Modern conformal techniques and daily image-guided radiation therapy protocols were used in 94% of centers. CONCLUSION: Our survey showed that re-RT treatment is performed with advanced technology that allow a good management of LR rectal cancer. Significant variations were observed in terms of dose and fractionation, highlighting the need for a consensus on a common treatment strategy that could be validated in prospective studies.

Whole breast radiotherapy in cN0 early breast cancer patients with pathological sentinel lymph nodes (pN1mic, pN1a) without axillary dissection: preliminary results of the observational LISEN trial.

PURPOSE: Axillary management remains unclear when sentinel lymph node (SLN) results are positive in cN0 patients with breast cancer (BC). The trial ACOSOG Z0011 represented a revolution with axillary lymph node dissection (ALND) omission in SLN+ patients, despite critiques regarding non-uniformity of radiation fields. We conducted an observational study (LISEN) where whole breast radiotherapy (WBRT) was planned with tangential fields without nodal irradiation in patients eligible for the Z0011 trial. METHODS: Inclusion criteria were female patients with histologically proven BC, cT1-2cN0, planned conservative surgery, no neoadjuvant therapy. Patients were stratified into two groups: micrometastatic (pN1mic, group 1) and macrometastatic (pN1a, group 2) lymph nodes. Tangential field WBRT was mandatory. Clinical outcomes were analysed, measured from surgery until the first event. RESULTS: In all, 199 patients underwent conservative surgery and SLN biopsy; 133 patients meeting criteria were analysed: 41 patients (30.8%) pN1mic and 92 (69.2%) pN1a. The 5­year disease-free survival (DFS) was 95.0% (85.9-100%) in group 1 and 93.0% (86.3-100.0%) in group 2 (p = 0.78). Overall survival (OS) was 100% (100-100%) in group 1 and 97.4% (92.4-100%) in group 2 (p = 0.74). For the whole cohort DFS and OS were 93.6% (88.2-99.4%) and 96.9% (91.5-100.0%), respectively. For groups 1 and 2, the 5­year outcomes were 5.0% (0.0-14.4%) and 2.3% (0.0-6.1%) for local recurrence (p = 0.51), and 6.2% (0.0-17.4%) and 7.0% (0.0-13.7%) for distant metastasis (p = 0.61), respectively. In group 1, regional recurrence (RR) and local regional recurrence (LRR) were 5.0% (0.0-14.1%; p = 0.13). In group 2, RR and LRR were 0.0% (0.0-0.0%). CONCLUSION: Our results showed good regional control in patients who met the Z0011 trial criteria. WBRT, without nodal surgery or RT, avoiding axillary morbidity, seems to be a good choice.

A randomized in vitro evaluation of transient and permanent cardiac implantable electronic device malfunctions following direct exposure up to 10 Gy.

BACKGROUND AND PURPOSE: High-dose 6­MV radiotherapy may cause cardiac implantable electronic devices (CIEDs) to malfunction. To assess CIED malfunctions resulting from direct exposure up to 10 Gy, 100 pacemakers (PMs) and 40 implantable cardioverter-defibrillators (ICDs) were evaluated. MATERIALS AND METHODS: CIEDs underwent baseline interrogation. In ICDs, antitachycardia therapies were disabled via the programmer while the detection windows were left enabled. A computed tomography (CT) scan was performed to build the corresponding treatment plan. CIEDs were "blinded" and randomized to receive single doses of either 2, 5, or, 10 Gy via a 6-MV linear accelerator (linac) in a water phantom. Twenty-two wireless telemetry-enabled CIEDs underwent a real-time session, and their function was recorded by the video camera in the bunker. The CIEDs were interrogated after exposure and once monthly for 6 months. RESULTS: During exposure, regardless of dose, 90.9% of the CIEDs recorded electromagnetic interference, with 6 ICDs (27.3%) reporting pacing inhibition and inappropriate arrhythmia detections. After exposure, a backup reset was observed in 1 PM (0.7% overall, 1% among PMs), while 7 PMs (5% overall, 7% among PMs) reported battery issues (overall immediate malfunction rate was 5.7%). During follow-up, 4 PMs (2.9% overall; 4% among PMs) and 1 ICD (0.7% overall; 2.5% among ICDs) reported abnormal battery depletion, and 1 PM (0.7% overall; 1% among PMs) reported a backup reset (overall late malfunction rate was 4.3%). CONCLUSION: Apart from transient electromagnetic interference, last-generation CIEDs withstood direct 6­MV exposure up to 10 Gy. Permanent battery or software errors occurred immediately or later only in less recent CIEDs.

Cone-beam computed tomography for organ motion evaluation in locally advanced rectal cancer patients.

PURPOSE: Due to a reported dose-response relationship in rectal cancer radiotherapy, a greater interest in dose intensification on small boost volume arises. Considering the need of an appropriate target movements evaluation, this retrospective study aimed to use cone-beam computed tomography (CBCT) for GTV and mesorectum organ motion (OM) evaluation, in locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemo-radiotherapy, in prone and supine position. METHODS: Thirty-two LARC patients were analyzed. GTV and mesorectum were delineated on MRI co-registrated with CT simulation. GTV and mesorectum OM was estimated on all CBCTs, performed during treatment, co-registrated with CT simulation. OM evaluation was obtained, as mean shift in left and right (L-R), postero-anterior (P-A) and cranio-caudal (Cr-C) directions. Volumes variability was calculated by DICE index. RESULTS: A total of 296 CBCTs were analyzed. Mean shifts of the GTV and mesorectum in prone position were - 0.16 cm and 0.15 cm in L-R direction, 0.28 cm and - 0.40 cm in P-A direction, and 0.14 cm and - 0.21 cm, in Cr-C direction; for supine position the mean shifts of the GTV were - 0.10 cm and 0.17 cm in R-L direction, 0.26 cm and - 0.23 cm in A-P direction, 0.09 cm and - 0.11 cm in Cr-C direction. Mean DICE index for GTV and mesorectum was 0.74 and 0.86, in prone position, and 0.78 and 0.89 in supine position, respectively. CONCLUSION: GTV and mesorectum OM was less than 4 mm in all directions in both positions, with a 1 mm less deviation in supine position. CBCTs resulted effective for OM assessment, and it could be an appropriate method for the implementation on an intensification treatment.

A Pattern of Care Report on the Management of Patients with Squamous Cell Carcinoma of the Anus-A Study by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Gastrointestinal Tumors Study Group.

Background and objectives: The diagnosis and therapy of squamous cell carcinoma of the anus may vary significantly in daily clinical practice, even if international guidelines are available. Materials and Methods: We conducted a pattern of care survey to assess the management of patients with anal cancer in Italy (38 questions). We analyzed 58 questionnaires. Results: Most of the respondents work in public and/or university hospitals (75.8%) in northern Italy (65.5%). The majority (88.0%) treat less than 20 patients/year. Common examinations for diagnosis and staging are anorectal endoscopy (84.5%), computed tomography scan (86.2%) and pelvic magnetic resonance imaging (MRI) (96.5%). The most frequently prescribed dose to primary tumor is 50-54 Gy (46.5-58.6%) for early stage disease and 54-59.4 Gy (62.1-32.8%) for locally advanced cases. Elective volumes are prescribed around 45 Gy (94.8%). Most participants use volumetric intensity modulated radiotherapy (89.7%) and a simultaneous integrated boost (84.5%). Concurrent radiotherapy, 5-fluorouracil and mitomycin is considered the standard of care (70.6%). Capecitabine is less frequently used (34.4%). Induction chemotherapy is an option for extensive localized disease (65.5%). Consolidation chemotherapy is rarely used (18.9%). A response evaluation is conducted at 26-30 weeks (63.9%) with a pelvic MRI (91.4%). Follow-up is generally run by the multidisciplinary tumor board (62.1%). Conclusions: Differences were observed for radiotherapy dose prescription, calling for a consensus to harmonize treatment strategies.

Role of upper abdominal reirradiation for gastrointestinal malignancies: a systematic review of cumulative dose, toxicity, and outcomes on behalf of the Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: Abdominal recurrences of gastrointestinal malignancies are common. Evidence in clinical studies has shown that re-irradiation (Re-I) is tolerable and efficient in different tumor locations. In contrast, little clinical data are available on normal long-term Re­I tolerance doses. A systematic review of upper abdominal Re­I was performed with the aim of exploring the cumulative dose, toxicity, and outcomes. METHODS: A computerized search was undertaken in MEDLINE, EMBASE, OVID, and the Cochrane database. Only studies reporting toxicity and/or outcomes were taken into consideration. To improve the comparability of the different Re­I regimens and assess the relationship between Radiotherapy (RT) dose and toxicity, the equivalent dose in 2­Gy fractions was calculated according to the linear quadratic model. RESULTS: Sixteen studies met the inclusion criteria, with the total patients numbering 408. Median follow-up Re­I ranged from 5.9 to 45 months. The median time elapsed since previous RT treatment was 15 months (2-162 months). Re­I prescription doses were variable (22.5 Gy in 3 fractions to 126.5 Gy with 125I). Cumulative doses calculated for acute- and late-responding tissues ranged from 67.25 to 136 Gy and 30.3 to 188.38 Gy, respectively. Comprehensively, the pooled ≥G3 toxicity was 12% (95%CI: 7.6-19%). The overall 1­year survival and local recurrence-free survival rates were 53.7% (95%CI: 45.6-63.2%) and 66.5% (95% CI: 58.7-75.4%), respectively. Pain improvement was reported in 66.9% of patients. CONCLUSION: Due to limited evidence as a result of the retrospective design of the majority of the studies, our review suggests that upper abdominal Re­I is effective in terms of local control and palliation, with a moderate rate of severe toxicities.

Is multidisciplinary management possible in the treatment of lung cancer? A report from three Italian meetings.

PURPOSE: To report criticisms and barriers to the "real-life" application of international guidelines and recent developments in the management of locally advanced non-small cell lung cancer (NSCLC) in Italy. METHODS: Three 2-day courses were organized. During the first day, experts in different fields of thoracic oncology gave their lecture on diagnosis and therapy for locally advanced NSCLC. During the second day, all participants were divided into four groups to discuss on a clinical case as a multidisciplinary team (MDT). The aim was to stimulate the discussion on practical issues in the management of NSCLC patients in the real-life practice. RESULTS: A total of 196 physicians were involved in the courses as learners. Invasive diagnosis of nodal disease for staging purposes, a priori definition of "surgical resectability" and a regular MDT with all crucial participants available were the three main key points identified for a good management of these patients. The main barriers to the clinical application of a good diagnostic and therapeutic approach to the patient were the absence of a regular and complete MDT in the South and Centre of Italy, while in the North of Italy, time for discussion of clinical cases in the MDT and waiting lists for staging and therapeutic interventions were deemed as the major concerns. CONCLUSION: The meetings showed that diagnosis and treatment of locally advanced NSCLC are still extremely variable between different Italian regions. Logistic issues, waiting lists, paucity of well-trained staff and expertise seem to be the main barriers to international guidelines application.

Magnetic resonance imaging (MRI) compared with computed tomography (CT) for interobserver agreement of gross tumor volume delineation in pancreatic cancer: a multi-institutional contouring study on behalf of the AIRO group for gastrointestinal cancers.

BACKGROUND: Due to the high soft tissue resolution, magnetic resonance imaging (MRI) could improve the accuracy of pancreatic tumor delineation in radiation treatment planning. A multi-institutional study was proposed to evaluate the impact of MRI on inter-observer agreement in gross tumor volume (GTV) and duodenum delineation for pancreatic cancer compared with computer tomography (CT). MATERIAL AND METHODS: Two clinical cases of borderline resectable (Case 1) and unresectable (Case 2) pancreatic cancer were selected. In two sequential steps, diagnostic contrast-enhanced CT scan and MRI sequences were sent to the participating centers. CT-GTVs were contoured while blinded to MRI data sets. DICE index was used to evaluate the spatial overlap accuracy. RESULTS: Thirty-one radiation oncologists from different Institutions submitted the delineated volumes. CT- and MRI-GTV mean volumes were 21.6 ± 9.0 cm3 and 17.2 ± 6.0 cm3, respectively for Case 1, and 31.3 ± 15.6 cm3 and 33.2 ± 20.2 cm3, respectively for Case 2. Resulting MRI-GTV mean volume was significantly smaller than CT-GTV in the borderline resectable case (p < .05). A substantial agreement was shown by the median DICE index for CT- and MRI-GTV resulting as 0.74 (IQR: 0.67-0.75) and 0.61 (IQR: 0.57-0.67) for Case 1; a moderate agreement was instead reported for Case 2: 0.59 (IQR:0.52-0.66) and 0.53 (IQR:0.42-0.62) for CT- and MRI-GTV, respectively. CONCLUSION: Diagnostic MRI resulted in smaller GTV in borderline resectable case with a substantial agreement between observers, and was comparable to CT scan in interobserver variability, in both cases. The greater variability in the unresectable case underlines the critical issues related to the outlining when vascular structures are more involved. The integration of MRI with contrast-enhancement CT, thanks to its high definition of tumor relationship with neighboring vessels, could offer a greater accuracy of target delineation.

Inter-observer variability of clinical target volume delineation in definitive radiotherapy of neck lymph node metastases from unknown primary. A cooperative study of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Head and Neck Group.

BACKGROUND: This study, promoted by Italian Association of Radiotherapy and Clinical Oncology (AIRO) Head and Neck Group, aimed to assess the current national practice of target volume delineation on a case of neck lymph node metastases from unknown primary evaluating inter-observer variability, in a setting of primary radiotherapy. MATERIALS AND METHODS: A case of metastatic neck lymph node from occult primary was proposed to 17 radiation oncologists. A national reference RT center was identified and considered as benchmark. Participants were requested to delineate target volumes. A structured questionnaire was administered. A comparison between following parameters of the CTVs was performed: centroids distances, Dice similarity index (DSI), Jaccard index and mean distance to agreement (MDA). Volume expressed in cubic centimeters and CTVs cranio-caudal extension were evaluated. RESULTS: Sixteen of 17 radiation oncologists recommended three CTVs dose levels. (CTV HD, CTV ID and CTV LD); CTV ID was not delineated by one of the participants and by the reference center. The distance between the reference centroid and the mean centroid of CTVs HD was 1.09 cm (0.36-3.99 cm); for CTV LD, a mean centroids distance of 2.45 (0.27-4.83 cm) was found, and for CTV HD, mean DSI is 0.48 and mean Jaccard index is 0.32 and MDA was 8.89 mm. CTV LD showed a mean DSI of 0.46, mean Jaccard index of 0.31 and MDA of 14.87 when compared to the reference. CONCLUSION: Many aspects concerning treatment optimization of cervical nodes metastases from occult primary remain unclear, and we found a notable heterogeneity of global radiotherapy management reporting discordances both in target volume delineation and volume prescription.

Hippocampal sparing approach in fractionated stereotactic brain VMAT radio therapy: A retrospective feasibility analysis.

Volumetric Modulated Arc Therapy (VMAT) techniques for fractioned stereotactic brain radiotherapy (FSBRT) can achieve highly conformal dose distribution to intracranial lesions. However, they can potentially increase the dose to hippocampus (H) causing neurocognitive toxicity during the first four months after irradiation. The purpose of this study was to assess the feasibility of hippocampal-sparing (HS) treatment plans in 22 patients with brain metastasis treated with VMAT technique. Firstly, we retrospectively analyzed hippocampal doses in all 22 VMAT original (not hippocampal-sparing, NHS) plans. Plans with hippocampal dose exceeding constraints (9 out of 22) were re-planned considering dose constraints on the hippocampus (H) and on hippocampal avoidance zone (HAZ) generated using 5 mm isotropic margin to the hippocampus. Conformity (CI) and homogeneity indexes (HI) on the target and MUs, were maintained as close as possible to the original plans. Mean CINHS and CIHS obtained were: 0.79 ± 0.11 and 0.81 ± 0.10, respectively (P = 0.75); mean HINHS and HIHS were 1.05 ± 0.02 and 1.04 ± 0.01 respectively (P = 0.72). In both sets of plans, the mean MU values were similar: 1033 ± 275 and 1022 ± 234 for NHS and HS respectively. In HS plans, the mean hippocampal dose was decreased by an average of 35%. After replanning, the Dmax (21.3 Gy) for HAZ and H was met by 45% (4/9) and 78% (7/9) of the NHS plans, respectively. The worst results were obtained for cases with target volumes extention closer than 12 mm to H, because of the difficulty to spare hippocampus without compromising target coverage. After replanning D40% constraint value (7.3 Gy) was met by all the 9 NHS plans. In conclusion, this study suggests that an hippocampal-sparing approach to FSBRT is feasible resulting in a decrease in the dose to the hippocampus without any loss in conformity or increase in treatment time.

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.

Parotid glands in whole-brain radiotherapy: 2D versus 3D technique for no sparing or sparing.

PURPOSE: Whole-brain radiotherapy is performed as standard therapy in patients with multiple brain metastases and in patients with more favourable prognosis such as lymphoma and small-cell lung carcinoma in the prophylactic setting. Because of the prognosis and the total prescribed dose, the parotid glands are not usually regarded as an organ at risk in whole-brain radiotherapy. Long-term survival can be expected in some of these patients and late toxicity can be observed, becoming essential to evaluate organs at risk, particularly the parotid glands even in metastatic patients. We compared the 2D with 3D technique to evaluate parotid glands involvement and received dose, and coverage of the clinical target volume. MATERIALS AND METHODS: Seven patients were considered. The prescribed dose was 30 Gy in ten fractions. On the same day and with the same set-up, all the treatment planning were performed using a 2D and 3D technique. A treatment plan was performed following same technical characteristics as the 2D technique. The parotid glands and whole brain were delineated. Dose-volume statistics were analysed. RESULTS: Dose-volume histograms of the parotid glands showed that 2/7 patients (28 %) received a mean dose >20 Gy. We found a lack of coverage of the clinical target volume in 6/7 patients. CONCLUSIONS: Planning whole-brain radiotherapy with only the 2D technique involves a risk of including parotid glands in the field and not covering the clinical target volume. The 3D technique should be systematically performed and the parotid glands should be regarded as an organ at risk in whole-brain radiotherapy.

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.

Radiochemotherapy in Anal Cancer: cCR, clinical outcomes and quality of life using two different treatment schedules.

AIM: Main endpoint was a response rate to therapy; secondary endpoints were disease-free survival, overall survival, acute and late toxicities, specially in terms of anorectal and urinary continence. BACKGROUND: Radiochemotherapy for anal cancer achieves a good clinical response, locoregional control, anal function preservation. However, oncologic outcomes can differ using radiotherapy plus fluorouracil and mytomicin vs. cisplatin and fluorouracil. METHODS: Between 2000 and 2012, 27 anal cancer patients receiving radiotherapy combined with two different radiochemotherapy schedules, fluorouracil and mytomicin (group A) and cisplatin plus fluorouracil (group B). The Kaplan-Meier method was also used to estimate local control, overall survival and disease free survival. Statistical significance between curves was evaluated using the Log-rank test. RESULTS: Complete pathological response was found in 85.2% of patients, with higher rates of response in the group A (100% vs. 63.6%, p = 0.039). No significantly difference was found between the two groups for the other endpoints. Low rates of both acute and late toxicities were recorded. CONCLUSION: Radiotherapy plus fluorouracil and mytomicin provide a better complete pathological response than radiotherapy plus cisplatin and fluorouracil and a greater rate of anal sphincter function preservation. Globally, radiochemotherapy of the anal cancer provides excellent clinical outcomes with a good profile of acute and late toxicity, without difference between the two groups studied.

A controlled study of a lecithinized delivery system of curcumin (Meriva®) to alleviate the adverse effects of cancer treatment.

A proprietary lecithin delivery system of curcumin (Meriva) was evaluated in a controlled study to assess its efficacy in alleviating the side effects of cancer chemo- and radiotherapy in 160 patients undergoing these treatments. In both cases, a semi-quantitative evaluation of the side effects was carried out using a visual analogue scale, assessing also the plasma free radical status in all patients. Results showed that lecithinized curcumin might alleviate the burden of side effects associated to chemo- and radiotherapy, suggesting that the anecdotal use of various preparations of curcumin as a supportive agent for cancer treatment is well worth a systematic investigation in larger scale clinical trials. The capacity of curcumin to upregulate anti-oxidative responses and downregulate inflammatory pathways could explain its beneficial effect in tempering the prolonged and systemic oxidative and inflammatory effects of cancer treatment, and the beneficial effects observed in the plasma oxidative status in all patients of the treatment group support this view.

Role of microRNA in response to ionizing radiations: evidences and potential impact on clinical practice for radiotherapy.

MicroRNAs (miRNA) are small, non-coding, RNAs with gene expression regulator roles. As an important class of regulators of many cellular pathways, miRNAs are involved in many signaling pathways and DNA damage repair processes, affecting cellular radiosensitivity. Their role has led to interest in oncological implications to improve treatment results. MiRNAs represent a great opportunity to enhance the efficacy of radiotherapy treatments-they can be used to profile the radioresistance of tumors before radiotherapy, monitor their response throughout the treatment, thus helping to select intensification strategies, and also to define the final response to therapy along with risks of recurrence or metastatization. Even though many interesting studies support such potential, nowadays most studies on patient data are limited to experiments profiling tumor aggressiveness and response to radiotherapy. Moreover many studies report different although not conflicting results on the miRNAs evaluated for each tumor type. Without doubt, the clinical potential of such molecules for radiotherapy is striking and of high interest.

Impact of Neoadjuvant Radiochemotherapy on Pathological Complete Response for Locally Advanced Rectal Cancer: A Mono Institutional Experience.

BACKGROUND/AIM: Neoadjuvant radiochemotherapy followed by surgery is a standard of care in locally advanced rectal cancer (LARC). Only a subgroup of patients can obtain a pathological complete response (pCR) and achieve good local control. However, the role of pCR on patient survival is debated. The aim of the study was to evaluate the impact of pCR on clinical outcomes and toxicities in LARC patients treated with dose intensification and concomitant capecitabine treatment in a neoadjuvant radiochemotherapy schedule. PATIENTS AND METHODS: This was a single Institution retrospective study including 178 patients. Mandard tumor regression grade (TRG) and pTNM staging system were used to classify pathological response and define pathological complete response (pCR). Patients were divided in: pCR (pT0N0) and Not-pCR (pT>0N>0), according to pTNM and in good responders (TRG1-2) and partial/not responders (TRG3-5), according to Mandard TRG. The Kaplan-Meier method was used to estimate OS, CSS, DFS and LC. RESULTS: A low severe toxicity rate was observed. Acute Grade 3 lower bowel toxicity and Grade 3 cutaneous toxicity were reported in 2 (1.1%) patients, respectively. Late Grade >3 lower bowel toxicity was reported in 6 patients (3%) and late Grade >3 cutaneous toxicity was registered in one patient. No other severe acute and late toxicities were reported. The 5- and 10-year OS, CSS, DFS and LC rates were 85% and 75%, 94% and 92%, 83% and 81%, 88% and 88%, respectively. We observed a pCR rate of 36% and a good responders rate of 62%, in our study population. Both groups showed better rates for each analyzed clinical outcome. CONCLUSION: Neoadjuvant radiochemotherapy with dose intensification in LARC patients resulted in favorable long-term oncological outcomes, pCR rate showed an optimal impact on OS and DFS with an acceptable toxicity.