An Explainable MRI-Radiomic Quantum Neural Network to Differentiate Between Large Brain Metastases and High-Grade Glioma Using Quantum Annealing for Feature Selection.

Solitary large brain metastases (LBM) and high-grade gliomas (HGG) are sometimes hard to differentiate on MRI. The management differs significantly between these two entities, and non-invasive methods that help differentiate between them are eagerly needed to avoid potentially morbid biopsies and surgical procedures. We explore herein the performance and interpretability of an MRI-radiomics variational quantum neural network (QNN) using a quantum-annealing mutual-information (MI) feature selection approach. We retrospectively included 423 patients with HGG and LBM (> 2 cm) who had a contrast-enhanced T1-weighted (CE-T1) MRI between 2012 and 2019. After exclusion, 72 HGG and 129 LBM were kept. Tumors were manually segmented, and a 5-mm peri-tumoral ring was created. MRI images were pre-processed, and 1813 radiomic features were extracted. A set of best features based on MI was selected. MI and conditional-MI were embedded into a quadratic unconstrained binary optimization (QUBO) formulation that was mapped to an Ising-model and submitted to D'Wave's quantum annealer to solve for the best combination of 10 features. The 10 selected features were embedded into a 2-qubits QNN using PennyLane library. The model was evaluated for balanced-accuracy (bACC) and area under the receiver operating characteristic curve (ROC-AUC) on the test set. The model performance was benchmarked against two classical models: dense neural networks (DNN) and extreme gradient boosting (XGB). Shapley values were calculated to interpret sample-wise predictions on the test set. The best 10-feature combination included 6 tumor and 4 ring features. For QNN, DNN, and XGB, respectively, training ROC-AUC was 0.86, 0.95, and 0.94; test ROC-AUC was 0.76, 0.75, and 0.79; and test bACC was 0.74, 0.73, and 0.72. The two most influential features were tumor Laplacian-of-Gaussian-GLRLM-Entropy and sphericity. We developed an accurate interpretable QNN model with quantum-informed feature selection to differentiate between LBM and HGG on CE-T1 brain MRI. The model performance is comparable to state-of-the-art classical models.

Where does chemotherapy stands in the treatment of ampullary carcinoma? A review of literature.

Ampullary carcinoma (AC) is a rare gastrointestinal tumor without clear treatment recommendations. The management of this tumor is usually extrapolated from the treatment of pancreatic, biliary duct and intestinal cancers. Few papers have studied the AC as an independent entity and yet succombs to several limitations. These studies were retrospective single institutional experiences with limited sample sizes recruited over a long period of time. Unlike metastatic ACs where chemotherapy is the only recommended option, localized AC once excised may be approached by either chemotherapy alone or concomitant chemoradiation therapy. In this review, we report the overall survival and recurrence factors of more than 1000 patients from all the studies treating exclusively ACs. We also review the medical treatment of this tumor and conclude to the necessity of multi-institutional randomized controlled studies for AC exclusively.

Optimum chemotherapy for the management of advanced biliary tract cancer.

Biliary tract cancers (BTCs) are highly fatal malignancies, which are often diagnosed at an advanced stage and have relatively poor prognosis. The treatment of patients with advanced BTC is systemic, based on chemotherapy or best supportive care, depending on their performance status. Despite clinical trials studying many chemotherapeutic regimens and targeted therapies for the treatment of BTC, the standard of care for advanced BTC remains the combination of gemcitabine with cisplatin. Many new molecules targeting proliferation and survival pathways, the immune response and angiogenesis are currently undergoing phase I and II trials for the treatment of advanced BTC with promising results.

Anal cancer treatment: current status and future perspectives.

Anal cancers (AC) are relatively rare tumors. Their incidence is increasing, particularly among men who have sex with other men due to widespread infection by human papilloma virus. The majority of anal cancers are squamous cell carcinomas, and they are treated according to stage. In local and locally advanced AC, concomitant chemoradiation therapy based on mitomycin C and 5-Fluorouracil (5-FU) is the current best treatment, while metastatic AC, chemotherapy with 5-FU and cisplatin remains the gold standard. There are no indications for induction or maintenance therapies in locally advanced tumors. Many novel strategies, such as targeted therapies, vaccination, immunotherapy and photodynamic therapy are in clinical trials for the treatment of AC, with promising results in some indications.

Optimum chemotherapy in the management of metastatic pancreatic cancer.

Pancreatic cancer is one of the most devastating solid tumors, and it remains one of the most difficult to treat. The treatment of metastatic pancreatic cancer (MPC) is systemic, based on chemotherapy or best supportive care, depending on the performance status of the patient. Two chemotherapeutical regimens have produced substantial benefits in the treatment of MPC: gemcitabine in 1997; and FOLFIRIONOX in 2011. FOLFIRINOX improved the natural history of MPC, with overall survival (OS) of 11.1 mo. Nab-paclitaxel associated with gemcitabine is a newly approved regimen for MPC, with a median OS of 8.6 mo. Despite multiple trials, this targeted therapy was not efficient in the treatment of MPC. Many new molecules targeting the proliferation and survival pathways, immune response, oncofetal signaling and the epigenetic changes are currently undergoing phase I and II trials for the treatment of MPC, with many promising results.

[Tolerance of adjuvant radiotherapy in the treatment of stage I seminoma]. / Tolérance de la radiothérapie dans le traitement adjuvant des séminomes testiculaires stade I.

OBJECTIVE: To assess the tolerance of adjuvant radiotherapy in the treatment of stage I seminoma post-orchiectomy. MATERIAL AND METHODS: Between 2001 and 2006, 21 men with stage I seminoma underwent 3D conformal radiotherapy 3 to 4 weeks post-orchiectomy. The total radiation dose was 2490 cGy divided into 15 sessions. Radiation was delivered by 2 antero-posterior fields using X-ray photons of 18 MV. Two types of radiation fields were used : para-aortic and ipsilateral iliac (dog leg) or para-aortic only. The average followup was 2 years 4 months with an interval of 4 to 58 months. Tolerance of treatment was evaluated according to criteria of the RTOG. RESULTS: Median follow-up time is 30 months. Disease-free survival was 100%. The most frequently encountered acute toxicity was gastrointestinal; mainly nausea and vomiting. Tolerance to treatment was better in the group receiving para-aortic radiotherapy alone (37% of grade II gastrointestinal toxicity vs 62%) CONCLUSION: The para-aortic irradiation for stage I seminoma gave satisfactory results with a better toxicity profile than the dogleg irradiation.

[Chemoradiotherapy in early stage Hodgkin's lymphoma]. / Chimio-radiothérapie dans les lymphomes de Hodgkin-Stades précoces.

OBJECTIVE: To evaluate the response to and toxicities of chemo-radiotherapy (CT-RT) in patients with early stage Hodgkin lymphoma treated in our institution. MATERIALS AND METHODS: Retrospective study of 42 patients with early stage Hodgkin lymphoma treated between 2002 and 2007. RESULTS: The age of patients ranges from 11 to 57 with a mean of 30.7 years; the sex-ratio is 0.8 (19 males and 23 females). There are 33 cases of nodular-sclerosing Hodgkin lymphoma, 6 of mixed cellularity, one lymphocyte-rich, one interfollicular and one granulomatous. As for the stages, 31 Hodgkin lymphomas are stage IIA, 6 stage IA, 3 bulky and 2 stage IAe. The ABVD protocol was given to 38 patients, the VBVP to 3 patients and the ABV to one patient. IFRT was used with dose ranging from 19.8 to 39.6 Gy. The acute toxicity of chemotherapy was hematologic only, grade 1 anemia accounting for 11.1% and grade 2 anemia for 14.8%, grade 1 leukopenia for 51.8%, grade 2 leukopenia for 333% and grade 3 leukopenia for 14.8%. Dysphagia, radiodermitis and radiomucositis were seen after radiotherapy, accounting for 16.5%, 4.6% and 9.1% respectively. No long-term toxicity of the combined therapy was found. During the follow-up period, one relapse occurred and no death was reported. CONCLUSION: The overall survival (OS), the disease free survival (DFS) and the toxicities of the combined therapy CT-RT of the patients with early stage Hodgkin lymphoma stage IA and IIA treated in our institution were similar to those seen in the literature.

Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience.

BACKGROUND: Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. METHODS: 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU) and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. RESULTS: This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96%) had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy) was completed by 22 patients (91.7%). Only 7 patients (36.8%) completed the total planned courses of chemotherapy. 2 local relapses (10%), 2 regional relapses (10%) and 2 distant relapses (10%) were recorded. Time to progression has not been reached. 9 patients (37.5%) died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8%) with 9 (36%) patients suffering grade 3 or 4 toxicity and 5 patients (20%) suffering from grade 3 or 4 neutropenia. 4 (17%) patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17%) and 1 patient developed a deep venous thrombosis and a pulmonary embolus. CONCLUSIONS: Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the full planned courses of chemotherapy. This is due to hematological toxicity, mainly febrile neutropenia. This should prompt us to review the subsequent chemotherapy protocol and make it more tolerable.

[Corticosteroids and radiotherapy in the treatment of Graves' ophthalmopathy]. / Efficacité de la radiothérapie orbitaire combinée a la corticothérapie dans la prise en charge de l'ophtalmopathie, basedowienne.

Graves' ophthalmopathy is a debilitating disease impairing the quality of life of affected individuals. The management of moderate-to-severe active Graves' ophthalmopathy is a major therapeutic challenge, and the treatment outcome is often unsatisfactory. We have carried out a retrospective study to assess the efficacy of combined orbital irradiation and systemic corticosteroids. Ten patients were included; all patients had received 20 Grays to the retrobulbar tissues in ten fractions, and oral or intravenous glucocorticoids. The main therapeutic outcome measures were the criteria of Donaldson and co-workers and a self-assessment evaluation. The quality of life outcome was also evaluated by the GO-QOL (Graves' ophthalmopathy quality of life) questionnaire. Seven patients (70%) demonstrated improvement in ocular parameters; the response was excellent in three cases, good in three cases and fair in one case. Three patients showed no response to the treatment. The self-assessment evaluation showed that 75% of patients were satisfied with the results of the treatment. Proptosis was the most responsive sign to radiation and steroids. A duration of the eye disease of more than 18 months was associated with less improvement and a higher failure of the treatment. Concerning the quality of life, the score for visual fonctionning was 882 +/- 18.2 after treatment, while the score for appearance was 63.3 +/- 23.3. In conclusion, a combination of orbital irradiation and systemic steroids is associated with 70% of favorable responses, but the quality of life is not restored in the same proportions and remains impaired after treatment.

Outcome and prognostic factors in the conservative treatment of breast cancer.

BACKGROUND: The aim of this retrospective study is to evaluate the results and identify prognostic factors in early breast cancer. MATERIALS AND METHODS: One hundred breast cancers, 79 stage I and 21 stage II, had a conservative treatment between September 1993 and February 1996. Median age was 57 years; median tumor size 15 mm. Pathology was infiltrating ductal carcinoma in 88%. All patients underwent a conservative surgery followed by external radiotherapy. Twenty-eight patients received adjuvant chemotherapy and 64 patients received hormonal therapy. The median follow-up was 100 months. RESULTS: The 10 years overall survival rate was 85% and the metastasis free survival rate was 88.5%. The 10 years local control rate was 85.7%. Women less than 45 years old had a worse prognosis. CONCLUSION: These high rates of survival and local control confirm that breast conservation therapy yields favorable results, and that age is a major risk factor in women with early breast cancer.

[The role of radiotherapy in the treatment of ductal carcinoma in situ of the breast]. / Role de la radiothérapie dans le traitement des carcinomes canalaires in situ du sein.

INTRODUCTION: The incidence of ductal carcinoma in situ (DCIS) of the breast discovered during screening mammography is rising. This finding has led to the possibility of further breast conservation. We reviewed in this article the role of radiotherapy in the context of breast conservation. MATERIAL AND METHODS: Randomized and nonrandomized trials as well as meta-analyses and textbooks dealing with radiotherapy for DCIS have been retrieved from the published literature. Databases for ongoing trials have also been checked. RESULTS: Non randomized studies showed a poor local control with surgery alone, with local recurrences varying between 20 and 40% at 10 years. The use of radiotherapy led to a significant decrease in local relapse thus giving the rationale for phase III trials evaluating the role of radiotherapy. To date there are four trials published dealing with radiotherapy for DCIS:EORTC 10853, NSABP B-17, SweDCIS and UKCCCR. All these studies showed a significant decrease in the local relapse to values around 15% at 10 years. This benefit did not however translate into any survival gain. The effect of radiotherapy was seen in all patients sub-groups. However, controversies about the necessity of irradiating all patients and about the dose of the radiation to deliver remain present. Ongoing trials trying to provide answers to these controversies are reviewed. CONCLUSIONS: Conservative surgery followed by radiotherapy to the whole breast to a dose of 50 Gy remains the standard for breast DCIS discovered with screening mammography. This treatment should be discussed with all patients until randomized data provide evidence of a low risk category that should not have adjuvant radiation. The use of a boost on the tumor bed remains to be discussed for young patients who have positive margins only until data derived from phase III trials are available.

[A five-year experience in conformational radiotherapy in the treatment of prostate cancer. Evaluation of acute toxicity in 131 patients]. / Radiothérapie conformationnelle dans le traitement du cancer de la prostate. Evaluation de la toxicité aiguë chez 131 patients.

PURPOSE: To evaluate the urinary and rectal toxicity secondary to 3D conformal radiotherapy for prostate cancer. MATERIAL AND METHODS: Between 1998 and 2003, 131 men with prostate cancer underwent 3D conformal radiotherapy with or without androgen deprivation. The different stages were: 2 T1b ; 40 T1c; 19 T2a; 16 T2b; 18 T2c; 33 T3a; 1 T3b and 2 T3c with Gleason score: 4-6 = 47%, 7 = 36% and 8-9 in 17% of the cases. The median patient age was 66 (48-87). Pretreatment PSA level was respectively < 10 ng/ml (41%). 10-20 ng/ml (30%) and > 20 ng/ml (29%). Of the 131 patients, 98 received androgen ablation therapy before radiation. The total radiation dose varied between 66 and 74 Gy, delivered with 18MV photons of the linear accelerator, the median follow up was 33 months (5-67). RESULTS: According to the RTOG grading (gr) for acute toxicity, we noticed 3gr 3 genitourinary (GU) toxicity and no gr3 gastro intestinal (GI) toxicity. There were 36 gr 1 and 12 gr 2 GI toxicity, 41 gr 1 and 22 gr 2 GU toxicity. The mean prostate volume was 41 cc for patients who received androgen ablation and 56 cc for the others (p < 0.002). The percentage of volume receiving more than 50 Gy (V50) was calculated, the median V50 was 32% (5-67) for the rectum and 35% (5-79) for the bladder CONCLUSION: The toxicity profile in this study is in the same range than those of the literature and of our previous study concerning our first 50 patients with prostate cancer treated with 3D conformal radiotherapy.