Prediction of post-radiotherapy recurrence volumes in head and neck squamous cell carcinoma using 3D U-Net segmentation

Locoregional recurrences (LRR) are still a frequent site of treatment failure for head and neck squamous cell carcinoma (HNSCC) patients. Identification of high risk subvolumes based on pretreatment imaging is key to biologically targeted radiation therapy. We investigated the extent to which a Convolutional neural network (CNN) is able to predict LRR volumes based on pre-treatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) scans in HNSCC patients and thus the potential to identify biological high risk volumes using CNNs. For 37 patients who had undergone primary radiotherapy for oropharyngeal squamous cell carcinoma, five oncologists contoured the relapse volumes on recurrence CT scans. Datasets of pre-treatment FDG-PET/CT, gross tumour volume (GTV) and contoured relapse for each of the patients were randomly divided into training (n=23), validation (n=7) and test (n=7) datasets. We compared a CNN trained from scratch, a pre-trained CNN, a SUVmax threshold approach, and using the GTV directly. The SUVmax threshold method included 5 out of the 7 relapse origin points within a volume of median 4.6 cubic centimetres (cc). Both the GTV contour and best CNN segmentations included the relapse origin 6 out of 7 times with median volumes of 28 and 18 cc respectively. The CNN included the same or greater number of relapse volume POs, with significantly smaller relapse volumes. Our novel findings indicate that CNNs may predict LRR, yet further work on dataset development is required to attain clinically useful prediction accuracy

An Extended Hypofractionated Palliative Radiotherapy Regimen for Head and Neck Carcinomas

BackgroundPalliative radiotherapy to patients with head and neck cancer is often necessary, but there is a substantial variation in the treatment regimens reported in the literature, and consensus on the most appropriate schedules does not exist. In order to minimize acute toxicity while at the same time trying to achieve prolonged tumor control, a long hypofractionated regimen has been used routinely in Denmark. In the current retrospective study, we investigated the outcome in patients intended for palliative radiotherapy with this regimen.Materials and methodsPatients with newly diagnosed head and neck cancer treated with palliative radiotherapy of 52–56 Gy in 13–14 fractions twice weekly from 2009 to 2014 were included. Patients were excluded if they had previously received radiotherapy. Data on disease location, stage, patient performance status (PS), treatment response, acute skin and mucosal toxicity, and late fibrosis were collected prospectively and supplemented with information from medical records.Results77 patients were included in the study. Fifty-eight patients (75%) completed the intended treatment. Loco-regional tumor response (complete or partial) was evaluated 2 months posttreatment and observed in 45% of the entire population corresponding to 71% of patients alive. PS had a significant influence on survival (p = 0.007) and on not completing the intended treatment. Grade III or IV acute mucositis were observed in 25%, and grade III or IV acute dermatitis observed in 15%.ConclusionPalliative hypofractionated radiotherapy with 52–56 Gy in 13–14 fractions shows good tumor response and tolerability in a vulnerable patient population. However, it may not be suited for patients in poor PS

Value of post-operative reassessment of estrogen receptor α expression following neoadjuvant chemotherapy with or without gefitinib for estrogen receptor negative breast cancer

International audienceThe NICE trial was designed to evaluate the possible benefits of adding epidermal growth factor receptor targeted therapy to neoadjuvant chemotherapy in patients with estrogen receptor α (ER) negative and operable breast cancer. Preclinical data have suggested that signalling through the ErbB receptors or downstream effectors may repress ER expression. Here the authors investigated whether gefitinib, given neoadjuvant in combination with epirubicin and cyclophosphamide (EC), could restore ER expression. Eligible patients in the NICE trial were women with unilateral, primary operable, ER negative invasive breast cancer ≥2 cm. Material from patients randomized and completing treatment (four cycles of neoadjuvant EC plus 12 weeks of either gefitinib or placebo) in the NICE trial having available ER status both at baseline and after neoadjuvant treatment were eligible for this study. Tumors with indication of changed ER phenotype (based on collected pathology reports) were immunohistochemically reassessed centrally. 115 patients were eligible for this study; 59 patients in the gefitinib group and 56 patients in the placebo group. Five (4.3%) of 115 tumors changed ER phenotype from negative to positive. A change was seen in three patients in the gefitinib (5.1%) and in two patients in the placebo (3.6%) group with a difference of 1.51% (95% CI, −6.1-9.1). Results of the NICE trial have been reported previously. Post-operative reassessment of ER expression changed the assessment of ER status in a small but significant fraction of patients and should, whenever possible, be performed following neoadjuvant chemotherapy for ER negative breast cancer. Gefitinib did not affect the reversion rate of ER negative tumors

Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial

International audienceGefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has shown both anti-proliferative and anti-tumoral activity in breast cancer. This study was designed to determine the effect of adding gefitinib to neoadjuvant epirubicin and cyclophosphamide (EC) on tumor response rates. Women with unilateral, primary operable, estrogen receptor negative invasive breast cancer ≥ 2 cm were eligible for inclusion. Randomized patients were to receive four cycles of neoadjuvant EC plus 12 weeks of either gefitinib (250 mg daily) or placebo. Primary endpoint was pathologic complete response (pCR), and secondary endpoints were complete response (CR) and overall objective response (OR). 181 patients were randomized. A pCR was observed in 17% (12/71) of patients treated with gefitinib and in 12% (9/73) of patients treated with placebo (4.57% difference, 95% CI −7.19 to 6.33;  = 0.44). CR was observed in 10% of patients in both the gefitinib (7/71) and the placebo group (7/73) (0.27% difference, 95% CI −9.6 to 10.2;  = 0.96). There was no significant difference in OR (5.96%; 95% CI −9.9 to 21.9;  = 0.45) between the two groups. Post hoc subgroup analysis showed a significant difference in pCR between triple negative breast cancer (TNBC) and non-TNBC tumors ( = 0.03). More patients in the gefitinib arm had hematological toxicity ( = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups. A significantly higher pCR rate was observed post hoc in TNBC versus non-TNBC independent of treatment. More patients in the gefitinib group discontinued treatment because of AE