Dosimetric Impact of Inter-Fraction Variability in the Treatment of Breast Cancer: Towards New Criteria to Evaluate the Appropriateness of Online Adaptive Radiotherapy.

Purpose: As a discipline in its infancy, online adaptive RT (ART) needs new ontologies and ad hoc criteria to evaluate the appropriateness of its use in clinical practice. In this experience, we propose a predictive model able to quantify the dosimetric impact due to daily inter-fraction variability in a standard RT breast treatment, to identify in advance the treatment fractions where patients might benefit from an online ART approach. Methods: The study was focused on right breast cancer patients treated using standard adjuvant RT on an artificial intelligence (AI)-based linear accelerator. Patients were treated with daily CBCT images and without online adaptation, prescribing 40.05 Gy in 15 fractions, with four IMRT tangential beams. ESTRO guidelines were followed for the delineation on planning CT (pCT) of organs at risk and targets. For each patient, all the CBCT images were rigidly aligned to pCT: CTV and PTV were manually re-contoured and the original treatment plan was recalculated. Various radiological parameters were measured on CBCT images, to quantify inter-fraction variability present in each RT fraction after the couch shifts compensation. The variation of these parameters was correlated with the variation of V95% of PTV (ΔV95%) using the Wilcoxon Mann-Whitney test. Fractions where ΔV95% > 2% were considered as adverse events. A logistic regression model was calculated considering the most significant parameter, and its performance was quantified with a receiver operating characteristic (ROC) curve. Results: A total of 75 fractions on 5 patients were analyzed. The body variation between daily CBCT and pCT along the beam axis with the highest MU was identified as the best predictor (p = 0.002). The predictive model showed an area under ROC curve of 0.86 (95% CI, 0.82-0.99) with a sensitivity of 85.7% and a specificity of 83.8% at the best threshold, which was equal to 3 mm. Conclusion: A novel strategy to identify treatment fractions that may benefit online ART was proposed. After image alignment, the measure of body difference between daily CBCT and pCT can be considered as an indirect estimator of V95% PTV variation: a difference larger than 3 mm will result in a V95% decrease larger than 2%. A larger number of observations is needed to confirm the results of this hypothesis-generating study.

Clinical Validation of a Deep-Learning Segmentation Software in Head and Neck: An Early Analysis in a Developing Radiation Oncology Center.

BACKGROUND: Organs at risk (OARs) delineation is a crucial step of radiotherapy (RT) treatment planning workflow. Time-consuming and inter-observer variability are main issues in manual OAR delineation, mainly in the head and neck (H & N) district. Deep-learning based auto-segmentation is a promising strategy to improve OARs contouring in radiotherapy departments. A comparison of deep-learning-generated auto-contours (AC) with manual contours (MC) was performed by three expert radiation oncologists from a single center. METHODS: Planning computed tomography (CT) scans of patients undergoing RT treatments for H&N cancers were considered. CT scans were processed by Limbus Contour auto-segmentation software, a commercial deep-learning auto-segmentation based software to generate AC. H&N protocol was used to perform AC, with the structure set consisting of bilateral brachial plexus, brain, brainstem, bilateral cochlea, pharyngeal constrictors, eye globes, bilateral lens, mandible, optic chiasm, bilateral optic nerves, oral cavity, bilateral parotids, spinal cord, bilateral submandibular glands, lips and thyroid. Manual revision of OARs was performed according to international consensus guidelines. The AC and MC were compared using the Dice similarity coefficient (DSC) and 95% Hausdorff distance transform (DT). RESULTS: A total of 274 contours obtained by processing CT scans were included in the analysis. The highest values of DSC were obtained for the brain (DSC 1.00), left and right eye globes and the mandible (DSC 0.98). The structures with greater MC editing were optic chiasm, optic nerves and cochleae. CONCLUSIONS: In this preliminary analysis, deep-learning auto-segmentation seems to provide acceptable H&N OAR delineations. For less accurate organs, AC could be considered a starting point for review and manual adjustment. Our results suggest that AC could become a useful time-saving tool to optimize workload and resources in RT departments.

Fractal-Based Radiomic Approach to Tailor the Chemotherapy Treatment in Rectal Cancer: A Generating Hypothesis Study.

INTRODUCTION: The aim of this study was to create a radiomic model able to calculate the probability of 5-year disease-free survival (5yDFS) when oxaliplatin (OXA) is or not administered in patients with locally advanced rectal cancer (LARC) and treated with neoadjuvant chemoradiotherapy (nCRT), allowing physicians to choose the best chemotherapy (CT) regimen. METHODS: LARC patients with cT3-4 cN0 or cT1-4 cN1-2 were treated according to an nCRT protocol that included concomitant CT schedules with or without OXA and radiotherapy dose of 55 Gy in 25 fractions. Radiomic analysis was performed on the T2-weighted (T2-w) MR images acquired during the initial tumor staging. Statistical analysis was performed separately for the cohort of patients treated with and without OXA. The ability of every single radiomic feature in predicting 5yDFS as a univariate analysis was assessed using the Wilcoxon-Mann-Whitney (WMW) test or t-test. Two logistic models (one for each cohort) were calculated, and their performance was assessed using the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: A total of 176 image features belonging to four families (morphological, statistical, textural, and fractal) were calculated for each patient. At the univariate analysis, the only feature showing significance in predicting 5yDFS was the maximum fractal dimension of the subpopulation identified considering 30% and 50% as threshold levels (maxFD30-50). Once the models were developed using this feature, an AUC of 0.67 (0.57-0.77) and 0.75 (0.56-0.95) was obtained for patients treated with and without OXA, respectively. A maxFD30-50 >1.6 was correlated to a higher 5yDFS probability in patients treated with OXA. CONCLUSION: This study suggests that radiomic analysis of MR T2-w images can be used to define the optimal concomitant CT regimen for stage III LARC cancer patients. In particular, by providing an indication of the gross tumor volume (GTV) spatial heterogeneity at initial staging, maxFD30-50 seems to be able to predict the probability of 5yDFS. New studies including a larger cohort of patients and external validation sets are recommended to verify the results of this hypothesis-generating study.

The Impact of Locoregional Treatment on Response to Nivolumab in Advanced Platinum Refractory Head and Neck Cancer: The Need Trial.

BACKGROUND: Previous locoregional treatment could affect the response to nivolumab in platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). The aim of this study is to evaluate the impact of the clinicopathological characteristics and previous treatment in predicting early progression to nivolumab in a real-world population. METHODS: This is an observational, multicenter retrospective/prospective study including patients (pts) with platinum refractory R/M HNSCC who received nivolumab 240 mg every 2 weeks from October 2018 to October 2019. We analyzed the association between previous treatment, clinicopathological characteristics, and early progression (within 3 months). RESULTS: Data from 61 pts were reviewed. Median age was 67 years (30-82). Forty-two pts (69%) received previous locoregional treatment. Early progression to nivolumab occurred in 36 pts (59%), while clinical benefit (stable disease and partial response) was achieved in 25 pts (41%). Early progression to nivolumab was significantly associated to previous locoregional treatment both at univariate and multivariate analysis (p = 0.005 and p = 0.048, respectively). CONCLUSION: nivolumab in R/M HNSCC is burdened with a high early progression rate. Previous wide neck dissection and high dose radiotherapy may compromise the efficacy of nivolumab, distorting the anatomy of the local lymphatic system and hindering the priming of immune response.

The impact of multidisciplinary team management on outcome of hepatic resection in liver-limited colorectal metastases.

Hepatic resection is the gold standard treatment for patients affected by liver-limited colorectal metastases. Reports addressing the impact of multidisciplinary team (MDT) evaluation on survival are controversial. The aim of this study was to evaluate the benefit of MDT management in these patients in our Institution experience. The objective of the analysis was to compare survivals of patients managed within our MDT (MDT cohort) to those of patients referred to surgery from other hospitals without MDT discussion (non-MDT cohort). Of the 523 patients, 229 were included in the MDT cohort and 294 in the non-MDT cohort. No difference between the two groups was found in terms of median overall survival (52.5 vs 53.6 months; HR 1.13; 95% CI, 0.88-1.45; p = 0.344). In the MDT cohort there was a higher number of metastases (4.5 vs 2.7; p < 0.0001). The median duration of chemotherapy was lower in MDT patients (8 vs 10 cycles; p < 0.001). Post-operative morbidity was lower in the MDT cohort (6.2 vs 21.5%; p < 0.001). One hundred and ninety-seven patients in each group were matched by propensity score and no significant difference was observed between the two groups in terms of OS and DFS. Our study does not demonstrate a survival benefit from MDT management, but it allows surgery to patients with a more advanced disease. MDT assessment reduces the median duration of chemotherapy and post-operative morbidities.

Palbociclib Plus Fulvestrant or Everolimus Plus Exemestane for Pretreated Advanced Breast Cancer with Lobular Histotype in ER+/HER2- Patients: A Propensity Score-Matched Analysis of a Multicenter Retrospective Patient Series.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) show meaningful efficacy and tolerability in patients with metastatic breast cancer (MBC), but the optimal sequence of ET has not been established. It is not clear if patients with lobular breast carcinomas (LBC) derive the same benefits when receiving second line CDK4/6i. This retrospective study compared the efficacy of palbociclib plus fulvestrant (PALBO-FUL) with everolimus plus exemestane (EVE-EXE) as second-line ET for hormone-resistant metastatic LBC. From 2013 to 2018, patients with metastatic LBC positivity for estrogen and/or progesterone receptors and HER2/neu negativity, who had relapsed during adjuvant hormonal therapy or first-line hormonal treatment, were enrolled from six centers in Italy in this retrospective study. A total of 74 out of 376 patients (48 treated with PALBO-FUL and 26 with EVE-EXE) with metastatic LBC were eligible for inclusion. Progression-free survival (PFS) was longer in patients receiving EVE-EXE compared with PALBO-FUL (6.1 vs. 4.5 months, univariate HR 0.58, 95% CI 0.35-0.96; p = 0.025). On the propensity score (PS) analysis, PFS was confirmed to be significantly longer for patients treated with EVE-EXE compared to PALBO-FUL (6.0 vs. 4.6 months, p = 0.04). This retrospective analysis suggests that EVE-EXE is more effective than PALBO-FUL for second line ET of metastatic LBC, allowing us to speculate on the optimal therapeutic sequence.

Is surgery mandatory in locally advanced gastrointestinal stromal tumors after imatinib? A case report and literature review.

Oesophageal gastrointestinal stromal tumors (GISTs) are rare neoplasms (about 2% of all GISTs); radical surgery is the standard treatment of all GISTs but in case of locally advanced and unresectable disease no clear treatment guide lines are available. Studies including neoadjuvant imatinib mesylate (IM) are relatively recent, includes small sample size of heterogeneous patients and do not report a standardized duration of neoadjuvant treatment. The main question still remains whether surgery after neoadjuvant IM gives a survival benefit in locally advanced disease. A 46-year-old man with locally advanced unresectable oesophageal GIST harboring KIT exon 11 mutation was treated in our institution for 12 months with neoadjuvant IM; a reduction of 83% of tumor volume was obtained in 9-month of neoadjuvant IM, but in the last 3 months no further response was seen. After neoadjuvant therapy, patient underwent radical surgery and adjuvant IM, which is still ongoing. Since no definitive data are available about survival benefit of surgery after neoadjuvant IM in locally advanced GISTs, a careful balance between morbidity and mortality derived from surgery should be considered and more studies are needed to better define the utility and the optimal duration of neoadjuvant treatment.