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Purpose: To evaluate the efficacy of concurrent radiochemotherapy in patients with stage III non-small cell lung cancer (NSCLC), and to examine the effect of hemoglobin levels on survival of those patients. The negative impact of anemia on survival has been noticed for other cancer sites including the head and neck, and the uterine cervix, but it has been rarely described in NSCLC cancer patients treated with radiotherapy. Methods: From April 1995 through March 2002, 56 patients with inoperable stage III non-small lung cancer were treated with radiotherapy consisting of 60 Gy (50 Gy+10 Gy boost) given in 30 fractions of 2 Gy daily, 5 days a week, over a period of 6 weeks, and concurrent low-dose daily chemotherapy (CHT) consisting of 6 mg/m2 of cisplatin given Mondays-Fridays during weeks 1–2 and 5–6. All patients had stage III disease and ages ranged from 39 to 81 years old (median 63.9 years). Results: The 2-year and 3-year survival rates were 34% and 16%, respectively. Patients with a pretreatment hemoglobin level superior or equal to 11.6 g/dl had a 2-year survival rate of 52% as compared to 15.5% for patients with a pretreatment hemoglobin level inferior to 11.6 g/dl (p=0.0075). Patients with higher KI (>70%) showed better survival rates than those with lower KI. Surprisingly, patients in stage IIIA did not survive significantly longer than those in stage IIIB. Hematological toxicity (grade ≥2) prevailed (25%), followed by esophageal (5.4%) and bronchopulmonary (2%) toxicity. Only three patients experienced acute grade 3 hematological toxicity. Because of acute toxic effects, irradiation was interrupted in 8 patients (14.3%) for 7–13 days (median 7.5 days). Late highgrade (≥3) toxicity was not found. No grade 4 toxicity or treatment-related deaths were observed during this study. Conclusion: Our data show that concurrent radiotherapy with daily low dose cisplatin is well tolerated, and shows survival rates comparable to more aggressive treatment regimens. A combination of this chemotherapy with accelerated hyperfractionated radiotherapy might improve the results in the future. Furthermore, we could show that the hemoglobin levels prior to therapy have an influence on the prognosis, where lower levels were associated with worse outcome. Further trials should consider supplementation with erythropoietin. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to evaluate and validate the use of the Geant4 application for emission tomography (GATE) Monte Carlo simulation platform for clinical intensity modulated radiotherapy (IMRT) dosimetry studies. Methods: The first step consisted of modeling a 6 MV photon beam linear accelerator (LINAC), with its corresponding validation carried out using percent depth dose evaluation, transverse profiles, tissue phantom ratio, and output factor on water phantom. The IMRT evaluation was performed by comparing simulation and measurements in terms of absolute and relative doses using IMRT dedicated quality assurance phantoms considering seven different patient datasets. Results: Concerning the LINAC simulated model validation tissue phantom ratios at 20 and 10 cm in water TPR1020 obtained from GATE and measurements were 0.672 ± 0.063 and 0.675, respectively. In terms of percent depth dose and transverse profiles, error ranges were, respectively: 1.472% ± 0.285% and 4.827% ± 1.323% for field size of 4 × 4, 5 × 5, 10 × 10, 15 × 15, 20 × 20, 25 × 25, 30 × 30, and 40 × 40 cm2. Most errors were observed at the edge of radiation fields because of higher dose gradient in these areas. Output factors showed good agreement between simulation and measurements with a maximum error of 1.22%. Finally, for IMRT simulations considering seven patient datasets, GATE provided good results with a relative error of 0.43% ± 0.25% on absolute dose between simulated and measured beams (measurements at the isocenter, volume 0.125 cm3). Planar dose comparisons were also performed using gamma-index analysis. For the whole set of beams considered the mean gamma-index value was 0.497 ± 0.152 and 90.8% ± 3.6% of the evaluated dose points satisfied the 5% / 4 mm criterion. Conclusions: These results show that GATE allows reliable simulation of complex beams in radiotherapy after an accurate LINAC modeling is validated. A simple cross-calibration procedure proposed in this work allows obtaining absolute dose values even in complex fields. [ABSTRACT FROM AUTHOR]

Abstract: Erythropoietin (EPO) is a glycoprotein hormone. This hormone is a growth factor for red blood cells precursors in the bone marrow. The decrease of oxygen partial pressure, a reduced number of erythrocytes caused by bleeding or excessive destruction, or increased tissues oxygen requirements lead to increased secretion of EPO. Its action takes place on bone marrow erythroblastic cells through specific receptors. EPO stimulates the proliferation of red cell precursors stem cells in the bone marrow, thus increasing their production in one to two weeks. The effectiveness of EPO at increasing haemoglobin and improving patients’ quality of life has been demonstrated by several studies. However, its use in radiotherapy remains controversial. While tumour hypoxia caused by anaemia is a factor of radio resistance and thus a source of local failure, tumour expression of EPO receptors presents a significant risk for tumour progression and neo-angiogenesis, which would be increased during the administration of EPO. The purpose of this article is to answer the question: is there a place for EPO in combination with radiotherapy in the management of cancer? [Copyright &y& Elsevier]

We present the updated recommendations of the French Society for Radiation Oncology on benign intracranial tumours. Most of them are meningiomas, vestibular schwannomas, pituitary adenomas, craniopharyngiomas, and glomus tumours. Some grow very slowly, and can be observed without specific treatment, especially if they are asymptomatic. Symptomatic or growing tumours are treated by surgery, which is the reference treatment. When surgery is not possible, due to the location of the lesion, or general conditions, radiotherapy can be applied, as it is if there is a postoperative growing residual tumour, or a local relapse. Indications have to be discussed at a multidisciplinary panel, with precise evaluation of the benefit and risks of the treatments. The techniques to be used are the most modern ones, as multimodal imaging and image-guided radiation therapy. Stereotactic treatments, using fractionated or single doses depending on the size or the location of the tumours, are commonly realized, to avoid as much a possible the occurrence of late side effects. [ABSTRACT FROM AUTHOR]

• The miscalibration of pulmonary and esophageal toxicities in patients with lung cancer treated by (chemo)-radiotherapy is frequent. • Usual dose-volume histograms do not account for dose spatial distribution. • Radiomics based models contribute to a significant improvement in acute and late pulmonary toxicities prediction. For acute esophageal toxicity, dosimetric and radiomics based models achieve similar results. (Chemo)–radiotherapy (RT) is the gold standard treatment for patients with locally advanced lung cancer non accessible for surgery. However, current toxicity prediction models rely on clinical and dose volume histograms (DVHs) and remain unsufficient. The goal of this work is to investigate the added predictive value of the radiomics approach applied to dose maps regarding acute and late toxicities in both the lungs and esophagus. Acute and late toxicities scored using the CTCAE v4.0 were retrospectively collected on patients treated with RT in our institution. Radiomic features were extracted from 3D dose maps considering Gy values as grey-levels in images. DVH and usual clinical factors were also considered. Three toxicity prediction models (clinical only, clinical + DVH and combined , i.e., including clinical + DVH + radiomics) were incrementally trained using a neural network on 70% of the patients for prediction of grade ≥2 acute and late pulmonary toxicities (APT/LPT) and grade ≥2 acute esophageal toxicities (AET). After bootstrapping (n = 1000), optimal cut-off values were determined based on the Youden Index. The trained models were then evaluated in the remaining 30% of patients using balanced accuracy (BAcc). 167 patients were treated from 2015 to 2018: 78% non small-cell lung cancers, 14% small-cell lung cancers and 8% other histology with a median age at treatment of 66 years. Respectively, 22.2%, 16.8% and 30.0% experienced APT, LPT and AET. In the training set (n = 117), the corresponding BAcc for clinical only/clinical + DVH/combined were 0.68/0.79/0.92, 0.66/0.77/0.87 and 0.68/0.73/0.84. In the testing evaluation (n = 50), these trained models obtained a corresponding BAcc of 0.69/0.69/0.92, 0.76/0.80/0.89 and 0.58/0.73/0.72. In patients with a lung cancer treated with RT, radiomic features extracted from 3D dose maps seem to surpass usual models based on clinical factors and DVHs for the prediction of APT and LPT. [ABSTRACT FROM AUTHOR]

Radiomics is a field that has been growing rapidly for the past ten years in medical imaging and more particularly in oncology where the primary objective is to contribute to personalised and predictive medicine. This short review aimed at providing some insights regarding the potential value of radiomics for cancer patients treated with radiotherapy. Radiomics may contribute to each stage of the patients' management: diagnosis, planning, treatment monitoring and post-treatment follow-up (toxicity and response). However, its applicability in clinical routine is currently hindered by several factors, including lack of automation, standardisation and harmonisation. A major effort must be carried out to automate the workflow, standardise radiomics good practices and carry out large-scale studies before any transfer to daily clinical practice. [ABSTRACT FROM AUTHOR]

Résumé: Le réseau lymphatique dense de l’œsophage favorise une extension tumorale rapide le long de la paroi et vers les relais ganglionnaires locorégionaux. Une meilleure connaissance de l’envahissement microscopique par les cellules tumorales, fondée sur l’analyse anatomopathologique de pièces opératoires et de l’observation des sites de récidive, a permis de réduire les volumes cible. La délinéation du volume cible anatomoclinique dépend des caractéristiques tumorales (site, type histologique) et de l’extension en imagerie [écho-endoscopie, tomographie par émission de positons (TEP) au (18F)-fluorodésoxyglucose (FDG)]. Nous proposons d’utiliser les valeurs prédictives positive et négative de la TEP au FDG pour adapter le volume cible anatomoclinique en fonction du risque d’atteinte ganglionnaire. [ABSTRACT FROM AUTHOR]

Abstract: PET imaging is now considered a gold standard tool in clinical oncology, especially for diagnosis purposes. More recent applications such as therapy follow-up or tumor targeting in radiotherapy require a fast, accurate and robust metabolically active tumor volumes delineation on emission images, which cannot be obtained through manual contouring. This clinical need has sprung a large number of methodological developments regarding automatic methods to define tumor volumes on PET images. This paper reviews most of the methodologies that have been recently proposed and discusses their framework and methodological and/or clinical validation. Perspectives regarding the future work to be done are also suggested. [Copyright &y& Elsevier]

Abstract: Introduction: Curative therapy for patients with small-cell lung cancer (SCLC) is based on multidrug chemotherapy combinations and radiotherapy. After a long time follow-up, the aim of the study was to evaluate the efficacy and toxicity of sequential chemo-radiotherapy and the effect of prophylactic cranial irradiation (PCI). Methods: From 1995–2005, 96 patients with SCLC (64 limited-disease [LD], 32 extensive-disease [ED]; median age 61years [range 39–79]) were treated at our department with varying chemotherapy regimens and sequential mediastinal radiotherapy (50Gy+10Gy boost in case of residual disease after chemotherapy). Afterwards, 15 patients with LD, good general condition and at least partial response after local treatment received PCI (30Gy). Results: After a median follow-up of 78.6months, 20 patients remained alive (20.8%, median survival time 18.2months). The 2-/5-year overall survival rates were 33.8% and 12.6%, the 2-/5-year loco-regional control rates were 30.3% and 24.5%, respectively. Distant metastases occurred in 43 patients (24 cerebral). Cerebral metastasis occurred in 6.7% and 27.2% of the patients with PCI and without PCI respectively. Only tumor stage showed a statistically significant impact on overall survival and loco-regional control in multivariate analysis. Radiotherapy was well tolerated. Grade 3/4 toxicity occurred in seven patients. Prognosis of patients with SCLC remains poor. Administration of PCI in selected patients bears a decrease in the incidence of cerebral metastases. Alternative chemotherapy schemes as well as irradiation schemes and techniques should be the substance of future randomized trials. [Copyright &y& Elsevier]

Abstract: Inverted papilloma (IP) is a rare nasosinusal benign tumour, with epithelium surface inversion to inside the stroma. Extension to intracranial temporal fossa and middle ear has been reported in few cases in the literature. This involvement may be derived from either direct extension from sinonasal cavity via the Eustachian tube or primary middle ear involvement secondary to metaplastic changes of the middle ear mucosa. Here, we report a case of inverted papilloma in a male patient, with multiple recurrences, middle ear and intracranial involvement into the temporal fossa with posterior development of malignancy. This patient had received multiple surgeries and radiotherapy but despite of that, his disease recurred several times. As a conclusion, inverted papilloma is a benign tumour with an aggressive course, tendency to recurrence and progression to malignancy. Intracranial and temporal fossa involvements are rare and the treatment depends of the symptoms and the severity of the disease. [Copyright &y& Elsevier]

Abstract: Background: Recent studies give rise to the hypothesis, that adjuvant chemoradioimmunotherapy with 5-fluorouracil (5-FU), cisplatin and interferon-α (IFN-α) might be a possible new treatment of pancreatic cancer in resected patients. We report the up-to-now experience at our institution. Patients and methods: Eleven patients with histological diagnosis of localized carcinoma of the pancreas (n =7) or periampullary (n =4) were prospectively analyzed. Four patients were deemed unresectable because of local invasion of adjacent organs (neoadjuvant setting) and seven patients underwent curative resection (adjuvant setting). Eight patients were classified as T3 carcinomas and three T4 carcinomas. Fifty-five per cent (6/11) of the patients presented with positive lymph node involvement. One histological Grade I, six Grade II and three Grade III were detected. External conformal irradiation to a total dose of 50.4 Gy with 1.8 Gy per day was delivered. All patients received a concomitant chemotherapy with continuous 5-FU 200mg/m2 per day on 28 treatment days and intravenous bolus cisplatin 30mg/m2 per week (Day 2, 9, 16, 23, 30). A recombinant r-IFN-α was administered on three days weekly during Week one to five of the radiotherapy course as subcutanous injections with 3*3 Mio. I.U. weekly. Results: The four-year overall survival rate for all patients was 55%. In the neoadjuvant group, three of four patients died due to progressive disease; in the adjuvant group, combined chemoradioimmunotherapy lead to controlled disease in five of seven patients. The overall toxicity was well-managed. Conclusion: Our data strengthens the hypothesis of concomitant chemoradioimmunotherapy with 5-FU, IFN-α and cisplatin as a possible new treatment of pancreatic cancer in resected patients. [Copyright &y& Elsevier]

Abstract: Purpose: To describe the clinical results and tolerance of the combined treatment with radiotherapy and cetuximab for locally advanced head and neck cancer. Patients and methods: From August 2006 and October 2010, 36 patients with advanced squamous cell head and neck carcinoma were treated with radiotherapy (70Gy/35 fractions) and cetuximab (400mg/m2 one week before radiotherapy, following by 250mg/m2 once weekly, until week 7 of radiotherapy). Tolerance was evaluated every week. All patients were examined every 3months the first 3years after therapy, and then every year. Results: The median follow-up was 14months. The majority of patients were male (31 out of 36). Mean age was 59years. The tumours sites were: oral cavity (n =8); oropharynx (n =15); hypopharynx (n =5); larynx (n =8). Ninety percent of tumors were T3 or T4, and 45% were N2 or N3. Complete response was seen in 74% of patients, partial response in 17% and no response in 9% of patients. The overall survival was 44.4%. Relapse occurred in six patients. Anaphylactic reaction during the first infusion of cetuximab was observed in one patient. One patient developed severe aplasia after 48Gy and 5weeks of cetuximab, and died of sepsis. Eighty percent of patients presented acne, 16 patients developed a mucositis grade 2–3 and 23 patients a grade 2 skin reaction. Conclusion: The concomitant use of cetuximab and radiotherapy in locally advanced head and neck carcinoma is well tolerated in this group of patients. The results seem comparable to those in the literature. [Copyright &y& Elsevier]