First case of Ethmoid Metastasis From an Induced Oropharyngeal Squamous Cell Carcinoma HPV, Interest of the P16 as a Diagnosis Aid.

We describe the first case of ethmoid metastasis from an oropharyngeal human papillomavirus-induced squamous cell carcinoma using the anti-P16 immunohistochemistry. The p16 overexpression can be a valuable aid in the differential diagnosis.

Domain adversarial networks and intensity-based data augmentation for male pelvic organ segmentation in cone beam CT.

In radiation therapy, a CT image is used to manually delineate the organs and plan the treatment. During the treatment, a cone beam CT (CBCT) is often acquired to monitor the anatomical modifications. For this purpose, automatic organ segmentation on CBCT is a crucial step. However, manual segmentations on CBCT are scarce, and models trained with CT data do not generalize well to CBCT images. We investigate adversarial networks and intensity-based data augmentation, two strategies leveraging large databases of annotated CTs to train neural networks for segmentation on CBCT. Adversarial networks consist of a 3D U-Net segmenter and a domain classifier. The proposed framework is aimed at encouraging the learning of filters producing more accurate segmentations on CBCT. Intensity-based data augmentation consists in modifying the training CT images to reduce the gap between CT and CBCT distributions. The proposed adversarial networks reach DSCs of 0.787, 0.447, and 0.660 for the bladder, rectum, and prostate respectively, which is an improvement over the DSCs of 0.749, 0.179, and 0.629 for "source only" training. Our brightness-based data augmentation reaches DSCs of 0.837, 0.701, and 0.734, which outperforms the morphons registration algorithms for the bladder (0.813) and rectum (0.653), while performing similarly on the prostate (0.731). The proposed adversarial training framework can be used for any segmentation application where training and test distributions differ. Our intensity-based data augmentation can be used for CBCT segmentation to help achieve the prescribed dose on target and lower the dose delivered to healthy organs.

Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial.

PURPOSE: Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. PATIENTS AND METHODS: The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. RESULTS: Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). CONCLUSION: Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy.

Improved Outcome by Adding Concurrent Chemotherapy to Cetuximab and Radiotherapy for Locally Advanced Head and Neck Carcinomas: Results of the GORTEC 2007-01 Phase III Randomized Trial.

Purpose To investigate the effect of adding concurrent chemotherapy (CT) to cetuximab plus radiotherapy (RT; CT-cetux-RT) compared with cetuximab plus RT (cetux-RT) in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Patients and Methods In this phase III randomized trial, patients with N0-2b, nonoperated, stage III or IV (nonmetastatic) LA-SCCHN were enrolled. Patients received once-daily RT up to 70 Gy with weekly cetuximab or with weekly cetuximab and concurrent carboplatin and fluorouracil (three cycles). To detect a hazard ratio (HR) of 0.64 for progression-free survival (PFS) with 85% power at a two-sided significance level of P = .05, 203 patients needed to be included in each arm. Results Four hundred six patients were randomly assigned to either CT-cetux-RT or cetux-RT. Patient and tumor characteristics were well balanced between arms, including p16 status. With a median follow-up of 4.4 years, the HR for PFS favored the CT-cetux-RT arm (HR, 0.73; 95% CI, 0.57 to 0.94; P = .015), with 3-year PFS rates of 52.3% and 40.5% and median PFS times of 37.9 and 22.4 months in the CT-cetux-RT and cetux-RT arms, respectively. The HR for locoregional control was 0.54 (95% CI, 0.38 to 0.76; P < .001) in favor of CT-cetux-RT. These benefits were observed regardless of p16 status for oropharynx carcinomas. Overall survival (HR, 0.80; P = .11) and distant metastases rates (HR, 1.19; P = .50) were not significantly different between the two arms. The CT-cetux-RT arm, compared with cetux-RT, had a higher incidence of grade 3 or 4 mucositis (73% v 61%, respectively; P = .014) and of hospitalizations for toxicity (42% v 22%, respectively; P < .001). Conclusion The addition of concurrent carboplatin and fluorouracil to cetux-RT improved PFS and locoregional control, with a nonsignificant gain in survival. To our knowledge, this is the first evidence of a clinical benefit for treatment intensification using cetux-RT as a backbone in LA-SCCHN.

Panitumumab as a radiosensitizing agent in KRAS wild-type locally advanced rectal cancer.

Our goal was to optimize the radiosensitizing potential of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, when given concomitantly with preoperative radiotherapy in KRAS wild-type locally advanced rectal cancer (LARC). Based on pre-clinical studies conducted by our group, we designed a phase II trial in which panitumumab (6 mg/kg/q2 weeks) was combined with preoperative radiotherapy (45 Gy in 25 fractions) to treat cT3-4/N + KRAS wild-type LARC. The primary endpoint was complete pathologic response (pCR) (H0 = 5%, H1 = 17%, α = 0.05, ß = 0.2). From 19 enrolled patients, 17 (89%) were evaluable for pathology assessment. Although no pCR was observed, seven patients (41%) had grade 3 Dworak pathological tumor regression. The regimen was safe and was associated with 95% of sphincter-preservation rate. No NRAS, BRAF, or PI3KCA mutation was found in this study, but one patient (5%) showed loss of PTEN expression. The quantification of plasma EGFR ligands during treatment showed significant upregulation of plasma TGF-α and EGF following panitumumab administration (p < 0.05). At surgery, patients with important pathological regression (grade 3 Dworak) had higher plasma TGF-α (p = 0.03) but lower plasma EGF (p = 0.003) compared to those with grade 0-2 Dworak. Our study suggests that concomitant panitumumab and preoperative radiotherapy in KRAS wild-type LARC is feasible and results in some tumor regression. However, pCR rate remained modest. Given that the primary endpoint of our study was not reached, we remain unable to recommend the use of panitumumab as a radiosensitizer in KRAS wild-type LARC outside a research setting.

A practice survey of the evolution of rectal cancer management: a Belgian Federal College of radiotherapy study.

The aim of the present study was to perform a rectal cancer practice survey in order to re-assess in 2005 the Belgian state of the art. A questionnaire based on the past 1999 peer review, supplemented with general questions, was circulated to 16 radiotherapy centres in Belgium. A case was also proposed for treatment planification. In 2005, a formal multidisciplinary team was in place in all visited centres. Endorectal ultrasound, colonoscopy, CEA and an initial pathological diagnosis were standard procedure in all centres. For T1-2N0, the majority of centres do not perform a preoperative treatment; for T3N0, a majority proposes a preoperative radiochemotherapy. For all T3-4 any N, or any T-N involved, a neoadjuvant preoperative treatment is prescribed. Fractionation is conventional (1.8 Gy/d, five times a week). Analysing the practical case, the mean value for CTV and PTV volume was 393 (SD: 126) and 781 cm3 (SD: 105), respectively. Mean D(min) and D(max) of 92 and 106.5%, respectively, were measured in the PTV. From clinical point of view, standards concepts are emerging and spreading for staging and for treatment options. Nevertheless, there is still a need for standardization of volumes and delineation standards.