Search

Second ipsilateral breast tumor event (2ndIBTE) occurring after primary radio-surgical treatment can be treated by either salvage mastectomy or 2nd conservative treatment (2ndCT) including an accelerated partial breast re-irradiation (APBrI). We analyzed the impact of the GEC-ESTRO APBI classification (GAC) on the oncological outcome after APBrI. Between 2000 and 2016, 159 patients (pts) underwent a 2ndCT. After lumpectomy, APBrI was performed using either low-dose (30–55 Gy reference isodose) or high-dose rate brachytherapy (28–34 Gy). Oncological outcome including 3rdIBTE, regional (RFS) or metastasis-free survival (MFS), specific (SS) and overall survival (OS) was analyzed according to GAC. Univariate (UVA) and multivariate analyses (MVA) were conducted to identify significant prognostic factors for 3rdIBTE. With a median follow-up of 71 months (range 62–85 months), 60 pts (42%), 61 pts (42.7%) and 22 pts (15.4%) were classified as low-risk (LR), intermediate-risk (IR) and high-risk (HR), respectively. For the whole cohort, 6-year 3rdIBTE-free survival, RFS, MFS, SS and OS rates were 97.4, 96.4, 90.3, 92.9 and 91.2%, respectively. Six-year 3rdIBTE-free survival rates for LR, IR and HR were 100, 95.8 and 92.9%, respectively (p = 0.003), while no significant differences were found between the three GAC groups for RFS, MFS, SS. In UVA, lympho-vascular invasion (p = 0.009), positive margins (p = 0.0001) and GAC high-risk group (p = 0.001) were considered as significant prognostic factors for 3rdIBTE, while, in MVA, high-risk group (p = 0.009) was the only prognostic factor. In case of 2ndIBTE, GAC could be used as a decision helping tool to discuss conservative or radical treatment options. Patient information remains crucial in order to accurately define the salvage therapy modalities.

Brachytherapy boost after external beam radiotherapy for intermediate and high-risk prostate cancer is presented as an attractive technique in numerous retrospective and prospective studies. Currently, three randomized controlled trials comparing brachytherapy versus external beam radiotherapy boost used non-homogenous irradiation features. Therefore, we analyzed the oncological outcomes by a systematic review with meta-analysis of the randomized controlled trials.We performed a systematic literature review of MEDLINE and COCHRANE databases up to 30/04/10 and we considered all published randomized controlled trials comparing brachytherapy versus external beam radiotherapy boost for intermediate and high-risk prostate cancer according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The review was assessed using Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool and the identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT). Eight publications from 3 RCTs were selected.There was a significant benefit in 5-year biochemical-progression-free survival in favor of BT versus EBRT boost (HR: 0.49 [95% CI, 0.37-0.66], p 0.01). There was no difference at 5 years in overall survival (HR: 0.92 [95% CI, 0.64-1.33], p = 0.65), ≥ grade 3 late genito-urinary (RR: 2.19 [95%CI, 0.76-6.30], p = 0.15) and late gastro-intestinal toxicities (RR: 1.85 [95%CI, 1.00-3.41] p = 0.05).This meta-analysis provides further evidence in favor of BT boost for intermediate and high-risk prostate cancer in terms of b-PFS improvement, leading to suggest BT boost as level I and grade A recommendation. However, the risk of grade ≥ 3 late toxicity must be carefully investigated.

Background Because of the rarity of the condition, studies concerning the management of patients with squamous cell carcinoma of the anus with distant metastasis are scarce. The available studies indicate poor outcomes with exclusive chemotherapy. Objective Our aim was to evaluate the impact of multidisciplinary treatment on overall survival among patients presenting with metastatic squamous cell carcinoma of the anus. Design This was a retrospective study. Settings The study was conducted at a single French institution between 2000 and 2014. Patients Consecutive patients with histologically proven, newly diagnosed, or recurrent metastatic squamous cell carcinoma of the anus were included. Interventions Study interventions included multimodal therapy combining systemic chemotherapy and local ablative treatment to remove all metastases through surgery, radiofrequency ablation, or radiotherapy. Main outcome measures The primary outcome measure was overall survival. Results Fifty patients (median age, 62 years; men/women: 8/42) fulfilled the inclusion criteria, and 39 were available for Response Evaluation Criteria in Solid Tumors. Forty had metastatic relapse after previous treatment of localized disease, and 10 presented with synchronous metastasis. P16 status was not available. Patients received at least 1 chemotherapy regimen, including 5-fluorouracil-mitomycin C (n = 22), cisplatin-5-fluorouracil (n = 20), or 5-fluorouracil alone (n = 3). Thirteen also had surgical metastasectomy, 11 had radiotherapy, and 6 had radiofrequency ablation. Median overall survival was 20.0 months (95% CI, 18.2-21.8 mo), and median time to failure of strategy was 6.0 months (95% CI, 2.9-9.1 mo). Overall response rate was 56% (95% CI, 40%-73%). Outcomes from the 5-fluorouracil-mitomycin C and cisplatin regimens did not statistically differ. Patients treated with multimodal therapy had a median overall survival of 22.0 months (95% CI, 15.3-28.6 mo) versus 13.0 months (95% CI, 9.5-16.5 mo; p = 0.002). Median time to failure of strategy was 10.0 months (95% CI, 4.2-15.7 mo) versus 5.0 months (95% CI, 2.8-7.2; p = 0.007). After 2 years, 40% of patients with multimodal treatment and 20% of those without ablative treatment were alive. Limitations This study is limited by its retrospective design and modest sample size. Conclusions Stage IV squamous cell carcinoma of the anus outcomes are poor, but first-line chemotherapy can enable good response rates. Other treatment modalities, including surgery, radiotherapy, and thermoablation, should be considered, because they may provide a survival advantage. See Video Abstract at http://links.lww.com/DCR/A336.

PD-1/PD-L1 inhibitors demonstrated durable clinical responses in patients with lung squamous cell carcinoma. However, the expression pattern of PD-L1 and the presence of CD8+ and PD-1+ tumor-infiltrating T cells in the basaloid variant of squamous cell carcinoma remain unknown. immunohistochemistry analysis of PD-L1 expression, with three recently validated monoclonal antibodies used in clinical trials (clones SP142, SP263, and 28-8), and detection of CD8+ and PD-1+ tumor-infiltrating T cells was performed on whole-tissue sections from 56 patients following surgery for basaloid squamous cell carcinoma. Data were correlated to clinicopathological parameters and outcome. Fair to poor concordance was observed between the SP142 vs SP263 clones, and SP142 vs 28-8 (κ range, 0.018-0.412), while the 28-8 and SP263 demonstrated a strong correlation in both the tumor cell and immune cell compartments (κ=0.883, and κ=0.721). Expression of PD-L1 correlated with a high content of CD8+ and PD-1+ tumor-infiltrating T cells when using SP142 (P=0.012; P=0.022), but not with SP263 or 28-8 (P=0.314; P=0.611). In the multivariate analysis, we found significantly better disease-free and overall survival rates for high PD-L1 expression with SP142, CD8+ and PD-1+ tumor-infiltrating T cells (P=0.003; P=0.007). No significant prognosis value was observed for SP263 and 28-8 clones, except a correlation between improved overall survival and SP263 in the univariate analysis (P=0.039), not confirmed in the multivariate model. In conclusion, we report that the expression of PD-L1 and the content of CD8+ and PD-1+ tumor-infiltrating T cells is an independent indicator of better outcome in basaloid squamous cell carcinoma patients, although the observed effect is dependent on the PD-L1 immunohistochemistry assay.

Resume Introduction Le score du MASCC, au moyen de criteres cliniques simples, permet de realiser une estimation du risque de survenue d’une complication grave au cours des neutropenies febriles induites par la chimiotherapie. Methodes Nous avons etudie une cohorte retrospective monocentrique francaise de patients pris en charge en hospitalisation pour une neutropenie febrile entre 2005 et 2012 et analyse les complications survenues au cours de l’hospitalisation en fonction des criteres definis par le MASCC. Resultats Au total, 81 episodes de neutropenie febrile concernant 71 patients ont ete repertories. Une documentation microbiologique etait obtenue dans 33 % des cas seulement. Pour 58 episodes de neutropenie febrile (72 %), le score MASCC etait superieur ou egal a 21 et les patients etaient consideres comme a faible risque de complications. Au total, 10 hospitalisations pour neutropenie febrile ont evolue vers le deces du patient, 7 dans le groupe a haut risque et 3 dans le groupe a bas risque, dont 2 patients presentant des comorbidites significatives non prises en compte par le score MASCC. Au sein du groupe a bas risque, la presence d’une maladie metastatique et l’existence d’au moins 2 comorbidites etaient associees a une duree significativement superieure d’hospitalisation. Conclusion Cette analyse suggere que les criteres du MASCC ne suffisent pas a identifier de maniere discriminante les patients a risque de complications et ceux pouvant etre traites en ambulatoire. La prise en compte des comorbidites et du stade tumoral doit donc contribuer a selectionner les patients susceptibles de recevoir un traitement ambulatoire.

Purpose To review current evidence of the role of proton therapy (PT) in other tumors than skull base, sinusal/parasinusal, spinal and pediatric tumors; to determine medico-economic aspects raised by PT. Material and methods A systematic review on Medline was performed with the following keywords: proton therapy, proton beam, protontherapy, cancer; publications with comparison between PT and photon-therapy were also selected. Results In silico studies have shown superiority (better dose delivery to the target and/or to organs at risk) of PT toward photon-therapy in most of thoracic and abdominal malignant tumors. Potential benefits of PT could be: reduction of toxicities (including radiation-induced cancer), increase of tumor control through a dose-escalation approach, hypofractionation. Cost of treatment is always cited as an issue which actually can be managed by a precise patient selection making PT a cost-effective procedure. Comparison plan with photon therapy may be useful to determine the dosimetric and clinical advantages of PT (Normal Tissue Complications Probability). Conclusion PT may be associated with a great advantage compared to the best photon-therapies in various types of cancers. Accumulation of clinical data is on-going and will challenge the in silico data analysis. Some indications are associated with strong superiority of PT and may be discussed as a new standard within prospective observational studies.

Introduction Prostate cancer local recurrence (PCLR) after definitive irradiation (external beam and/or brachytherapy) can be considered for local treatment in EAU-ESTRO-SIOG guidelines such as surgery, cryotherapy, high intensity ultra-sound or brachytherapy. We therefore performed a literature review of the role of stereotactic body radiation therapy (SBRT) in re-irradiation of PCLR.

Purpose The aim of this study was to evaluate the efficacy and toxicity of high-dose-rate brachytherapy (HDR-BT) boost in anal squamous cell carcinoma (ASCC). Material and methods This was a monocentric retrospective study involving patients treated by external irradiation (± chemotherapy), with HDR-BT boost, for a localized ASCC. Clinical evaluation was performed every six months. Oncological results were analyzed with: local relapse-free survival (LRFS), colostomy-free survival (CFS), metastatic-free survival (MFS), disease-free survival (DFS), and overall survival (OS). Acute and late toxicities were collected (CTCV4.0) and LENT/SOMA score was performed. Results From May 2005 to January 2018, 46 patients (pts) were analyzed. The median follow-up was 61 months (10-145 months), the median age was 65 years (34-84 years), with a sex ratio M/F = 0.24. The TNM classification was as follows: T1 - 13 pts (21.7%), T2 - 34 pts (73.9%), T3 - 2 pts (4.3%), N+ - 6 pts (13.1%). External beam radiotherapy (EBRT) delivered a median dose of 45 Gy (36-50.4 Gy) in 25 fractions, and HDR-BT 12 Gy (10-18 Gy) in 3 fractions. The median overall treatment time (OTT) was 58 days (41-101 days), with a median EBRT/brachytherapy interval of 17 days (4-60 days). Oncological findings showed 5-year rates of LRFS 81.2%, MFS 88.7%, DFS 70%, and OS 90%. All abdominoperineal amputations were performed in case of local relapse (4 pts, 8.7%), leading to a 5-year CFS of 79.5%. Acute urinary toxicities were frequent (G1 41.3%, G2 4.3%). The acute digestive toxicities were: G1 71.7%, G2 6.5%, and G3 2.2%. The late urinary toxicities were: G1 4.3%, G2 2.2%, and G3 2.2%. Late digestive toxicities were: G1 56.5%, G2 8.7%, G3 2.2%, and G4 2.2%. Conclusions In ASCC management, HDR-BT boost appears to be a treatment with a long-term acceptable toxicity profile, shorter than EBRT boost, with a reduction of side effects.

Objectives The effect of anti-PD-1/PD-L1 inhibitors on lung adenocarcinomas (LADCs) with KRAS mutations is debatable. We examined the association between specific mutant KRAS proteins and the immune infiltrates with the outcome of patients with LADCs. Patients and methods In 219 LADCs harboring either wild-type (WT) or mutated KRAS gene, we quantified the density of several immune markers by immunohistochemistry followed by automated digital image analysis. Data were correlated to clinicopathological parameters and outcome of patients. Results Tumors harboring mutant KRAS-G12 V had a significantly higher PD-L1 expression compared to other tumors (p = 0.044), while mutant KRAS-G12D tumors showed an increase in the density of CD66b+ cells (p = 0.001). High PD-L1 expression in tumor cells was associated to improved overall survival (OS) in KRAS mutant patients (p = 0.012), but not in the WT population (p = 0.385), whereas increased PD-L1 expression in immune cells correlated to poor OS of KRAS-WT patients (p = 0.025), with no difference in patients with KRAS mutations. Conclusions KRAS mutational status can affect the immune microenvironment and survival of LADC patients in a heterogeneous way, implying that specific mutant KRAS variants expressed by the tumor should be considered when stratifying patients for immunotherapy.

BACKGROUND AND PURPOSE Intensity-modulated radiation therapy (IMRT) is currently indicated to treat anal squamous cell carcinoma (ASCC). Conformal dose delivery and steep dose gradients may cause marginal misses. We analyzed patterns of locoregional recurrences (LRR) and delineation quality to determine IMRT-specific predictive factors. MATERIAL AND METHODS Lymph node area delineation was classified as "compliant" or "non-compliant" according to experts' workgroup recommendations. The recurrence volume (Vrecur) was delineated on initial planning-CT by recurrence imaging registration. The Vrecur was determined to be "in-field" (IF), "marginal" (ML), or "out-of-field" (OF) in regard to the 95% isodose coverage. RESULTS Out of 165 patients, 30 had LRR. Among the 27 local recurrences (LR), 20 (74%) were IF, 4 (15%) ML, and 2 (7%) OF. Fourteen patients had regional recurrence (RR), amounted to 33 separate recurrence sites (RS). RS were mostly localized in inguinal (n = 12;36,4%), external iliac (n = 7;21.1%), presacral (n = 4;12.1%) and common iliac (n = 3;9.1%) nodes. Eighteen (54.5%) RS were IF, 6 (18.2%) ML, and 9 (27.3%) OF. Performance status ≥2 (p = 0.007) and active smoking (p = 0.025) were predictors of LR. Immunodepression (p = 0.012), external iliac involvement (p

Purpose: There is no consensus for parametrial boost technic while both transvaginal and transperineal approaches are discussed. A prototype was developed consisting of a perineal template, allowing transperineal needle insertion. This study analyzed acute toxicity of concomitant cervical and transperineal parametrial high-dose-rate brachytherapy (HDRB) boost for locally advanced cervical cancer. Material and methods: From 01.2011 to 12.2014, 33 patients (pts) presenting a locally advanced cervical cancer with parametrial invasion were treated. After the first course of external beam radiation therapy with cisplatinum, HDRB was performed combining endocavitary and interstitial technique for cervical and parametrial disease. Post-operative delineation (CTV, bladder, rectum, sigmoid) and planification were based on CT-scan/MRI. HDRB was delivered in 3-5 fractions over 2-3 consecutive days. Acute toxicities occurring within 6 months after HDRB were retrospectively reviewed. Results: Median age was 56.4 years (27-79). Clinical stages were: T2b = 23 pts (69.7%), T3a = 1 pt (3%), T3b = 6 pts (18.2%), and T4a = 3 pts (9.1%). Median HDRB prescribed dose was 21 Gy (21-27). Median CTVCT (16 pts) and HR-CTV MRI (17 pts) were 52.6 cc (28.5-74.3), 31.9 cc (17.1-58), respectively. Median EQD2αβ10 for D90CTV and D90HR-CTV were 82.9 Gy (78.2-96.5), 84.8 Gy (80.6-91.4), respectively. Median EQD2αβ3 (CT/MRI) for D2cc bladder, rectum and sigmoid were 75.5 Gy (66.6-90.9), 64.4 Gy (51.9-77.4), and 60.4 Gy (50.9-81.1), respectively. Median follow-up was 14 months (ranged 6-51). Among the 24 pts with MFU = 24 months, 2-year LRFS rate, RRFS, and OS were 86.8%, 88.8%, and 94.1%, respectively. The rates of acute genitourinary and gastrointestinal toxicities were 36% (G1 dysuria = 8 pts, G2 infection = 2 pt, G3 infection = 2 pts), and 27% (G1 diarrhea = 9 pts), respectively. One patient presented vaginal bleeding at the time of applicator withdrawal (G3-blood transfusion); no bleeding was observed due to the parametrial implant. Conclusions : Concomitant cervical and transperineal parametrial HDRB boost for locally advanced cervical cancer appears feasible and safe with no specific acute toxicity compare to cervical HDRB alone. Longer follow-up and larger patient cohort will be needed.

Background: The elderly population in Western countries is growing and constitutes a public health issue. Concomitantly, age-related diseases such as cancer increase. There are few data on the efficacy, tolerability and toxicity of specific anticancer therapy in the very elderly patients; therefore, their management is not standardized. Methods: In this bi-institutional study, we reviewed medical records of patients who received or continued specific anticancer therapy beyond the age of 90 years. Geriatric assessment was not reported for our patients. Twelve patients were enrolled. Their general health condition was good, and half of them were living in elderly institutions. Ten patients had a solid tumor and 2 were treated for hematological malignancies. Most were diagnosed with a locally advanced or metastatic disease, and the goal of treatment was curative for only 1 patient. Six patients received chemotherapy as first-line treatment, 4 patients received targeted therapy and 2 received concomitant chemoradiation. Four patients received a second-line treatment. Results: Despite a significant reduction in treatment posology in half of the patients, 8 acute grade 3/4 toxicities were reported and 2 patients died of treatment-related septic shock. Median duration of first-line treatment was 3.2 months, and progression-free survival ranged from 18 to 311 days. Overall survival ranged from 18 days to 11 years. Conclusion: Aging is a heterogeneous process, and management of elderly patients is a multidisciplinary approach. Geriatric assessment helps to identify older patients with a higher risk of morbidity/mortality and allows to assess the risks and benefits of specific anticancer therapy. The choice of treatment should be based primarily on the expected symptomatic benefit, and treatment should not compromise the quality of life.

Lung cancer is a major public health concern worldwide. Progress in improving 5-year survival is lagging behind comparable survival rates in other common cancers. The majority of patients with locally advanced non-small cell lung cancer (NSCLC) are not suitable for surgical resection, hence the major role of radical radiotherapy. Advances in radiotherapy techniques allow targeted treatment of the disease, whilst minimizing the dose to organs at risk. Recent research into fractionation schedules, with hyperfractionated and accelerated radiotherapy regimens has been promising. Platinum-based chemotherapy has long been the standard of care for the initial treatment of advanced NSCLC. However, if radical radiotherapy remains the cornerstone of treatment for patients with unresectable advanced NSCLC either as single modality treatment or with concomitant chemotherapy, advances in understanding of tumor molecular biology and targeted drug development should bring targeted agents into the NSCLC management. The development of numerous therapeutic approaches has made the locally advanced NSCLC world change. An up-to-date overview of the current literature on updated chemotherapeutic agents, targeted therapy, immunotherapy, radiotherapy in stage III NSCLC is provided.

Background: Invasive fungal infections (IFIs) remain one of the worrying complications in patients with acute myeloid leukemia (AML) due to their incidence and high level of attributable mortality. In light of these risks, antifungal prophylaxis has always been debated. We conducted a single-center retrospective study of two prophylactic antifungal agents (fluconazole/posaconazole) in 91 consecutive patients receiving induction chemotherapy for AML between 2005 and 2009, in order to evaluate the impact on the incidence of IFI and on the mycological flora of the patients. Methods: In total, 39 patients received prophylactic fluconazole versus 52 who received posaconazole. The baseline characteristics of the two groups were comparable. Results: Overall, 17 patients developed an IFI, with no difference in frequency between the two groups. Utilization of empirical or pre-emptive therapy was similar irrespective of the type of prophylaxis used. Mycological examination of stools revealed an increase in non- albicans Candida colonization in the fluconazole group during hospitalization and the appearance of Saccharomyces cerevisiae colonization in patients receiving posaconazole. Conclusion: The present study does not distinguish between fluconazole and posaconazole as a primary effective prevention against fungal infections. More prospective studies and meta-analyses are warranted.

There are only scarce data on the optimal management of patients who present with a bladder carcinoma and who are aged 90 years and older. We retrospectively reviewed records from radiotherapy departments from two university hospitals, two private centers and one public center to identify patients who underwent radiotherapy for bladder cancer over the past decade and who were aged 90 years or older. From 2003 to 2013, 14 patients aged 90 years or older receiving RT for bladder malignant tumors were identified. Mean age was 92.7 years. Ten patients (71 %) had a general health status altered (PS 2–3) at the beginning of RT. A total of 14 RT courses were delivered, including six treatments (43 %) with curative intent and eight treatments (57 %) with palliative intent. Palliative intent mainly encompassed hemostatic RT (36 %). At last follow-up, two patients (14 %) experienced complete response, one patient (7 %) experienced partial response, three patients (21 %) had their disease stable, and three patients (21 %) experienced tumor progression, of whom two patients with the progression of symptoms. There was no reported high-grade acute local toxicity in 14 patients (100 %). One patient experienced delayed grade 2 toxicity with pain and lower urinary tract symptoms. At last follow-up, seven patients (50 %) were deceased. Cancer was the cause of death for five patients. Hypofractionated radiotherapy remains feasible for nonagenarians with bladder cancer. Further investigations including analysis of geriatric comorbidities and impact of treatments on quality of life should be conducted.

Purpose Currently, there are no recommendations for the management of a second local recurrence of prostate adenocarcinoma except for the introduction of androgen deprivation therapy (ADT). Case report A 69-year-old man underwent a third salvage local treatment with high-dose-rate brachytherapy (HDRB), for a second biochemical relapse for local recurrence. Thirty-five Grays in 5 fractions were delivered on the whole prostate extended to the proximal part of left seminal vesicle. Given the availability of new treatment techniques in our radiation therapy department, a dosimetric comparison between HDRB and stereoatactic radiosurgery (SRS) was performed. Results Immediate tolerance of HDRB was acceptable with achievement of prostate specific antigen (PSA) nadir in 24 months (0.03 ng/ml). Observed late toxicities were only grade 2 urinary incontinence. Dosimetric comparison showed a slight advantage on clinical target volume coverage and rectum protection for the SRS. The HDRB showed an advantage on bone irradiation including femoral heads and the volume receiving 0.5 Gy (EQD2 = 1 Gy with α/β = 3). Conclusions A third local treatment with good tolerance could be a therapeutic option in case of a second local prostate cancer recurrence in order to delay, as long as possible, the chemical castration. Both techniques (HDRB and SRS) seem valid and should be chosen based on the availability and experience in a treatment center.

No consensus exists regarding the role of radiotherapy in the management of gynecologic cancer in nonagenarian patients. We retrospectively reviewed the outcomes of 19 consecutive nonagenarian patients with gynecologic cancer (6 endometrial cancers, 6 cervical cancers, 4 vulvar cancers, and 3 vaginal cancers) who were treated with radiotherapy. Radiotherapy was performed mainly in a palliative setting (n = 12; 63.2%), with a median dose of 45 Gy (range, 6–76 Gy). Infrequent major acute or late toxicities were reported. Among 19 patients, 9 (47.4%) experienced tumor progression, 5 (26.3%) experienced complete response, 2 (10.5%) experienced stable disease and/or partial response. At last follow-up, 12 patients (63.2%) had died; most deaths (n = 9) occurred because of the cancer. These results suggest that radiotherapy is feasible in the treatment of nonagenarian patients with gynecologic cancer.

Objective: Several studies have demonstrated that daily physical activity (PA) prevents the development of breast cancer. Our objective was to examine the relationship between PA and clinical and biological tumor characteristics in breast cancer patients in order to determine the impact of energy expenditure (EE) on tumor prognosis. Methods: We pooled data from two prospective studies, including a total of 121 breast cancer patients. The measure of PA was done using the self-completion Population Physical Activity Questionnaire, which was answered by each patient. Results: Ten patients harbored triple negative (TN) tumors. The mean body mass index (BMI) in the general population and in patients with TN tumors was 24.3 and 25.6, respectively. The mean daily EE (DEE) was 10,266 kJ × 24 h-1 in the general population and 11,212 kJ × 24 h-1 in patients with TN tumors. In the whole population, there was an inverse statistical correlation between BMI and DEE, rest, low PA, and high PA (p = 0.0002, p = 0.003, p < 0001, and p = 0.03, respectively). There was a positive correlation between negative estrogen receptor status and intensive PA (p = 0.041) and DEE (p = 0.007). For TN tumors, there was no significant correlation between BMI and categories of EE. Conclusions: Lifestyle (weight regulation, PA) should be adapted and personalized according to biological, clinical, and epidemiological characteristics of the tumors.

The advent of genomic based precision medicine led to the implementation of biomarker testing in metastatic non-small cell lung cancer (NSCLC) patients. Next generation sequencing (NGS) has been recently implemented to routine diagnostic requirements in lung oncology. Areas covered: Two cases of patients with metastatic NSCLC for whom NGS analysis performed on both tumor and liquid biopsy has not improved the clinical course of their disease are reported. These cases illustrate the difficulty of the so-called 'personalized or precision' medicine in clinical routine practice for metastatic NSCLC. Expert commentary: Discovery and detection of critical cancer-gene alterations better indicates targeted therapies that must be administered to improve the care of NSCLC patients in the personalized medicine era. There has been much interest in the literature and the scientific community for NGS tailored therapies approach for patients. However, there may be a gap between this theoretical stratified medicine and clinical practice. The advantages and drawbacks of NGS on tumor tissue and cell-free DNA for metastatic NSCLC are discussed.

Purpose Dose escalation for prostate cancer can be achieved with a combination of external beam radiotherapy (EBRT) and brachytherapy (BT) boost to increase local control. For high-dose-rate (HDR)-BT, optimal fractionation remains under debate. The objective was to assess the clinical outcome of three schemes of HDR-BT boost. Methods and Materials Retrospective single institution data collection was performed. Patients received 46 Gy EBRT then an HDR-BT boost: 3 × 6 Gy, 2 × 9 Gy, or 1 × 14 Gy. HDR needles were placed under general anesthesia with endorectal ultrasonography guidance. CT-scan and treatment were performed postoperatively. Results Between 2009 and 2012, 159 patients were included. Nine patients (5.7%) were low, 32 (20.1%) intermediate, and 118 (74.2%) high risk (D'Amico classification) without significant difference between the three BT schemes. With a median followup of 61 months, 5-year biochemical relapse–free survival, 5-year local relapse–free survival, 5-year metastases-free survival, and 5-year overall survival rates were 86.6% (SE 2.7%), 98.3% (SE 1%), 95.3% (SE 1%), and 96.5% (SE 1.5%), respectively, with no significant difference between the BT schemes. The rates of acute ≥ G2 genitourinary and ≥G2 gastrointestinal toxicities were 11.3% and 6.3%, respectively (p = NS). The rates of late genitourinary ≥ G2 and gastrointestinal ≥ G2 toxicities (at last followup) were 9.4% and 0.6% with, respectively, 0.6% and 0% of G4 (p = NS). Conclusions Hypofractionation up to a single-fraction HDR-BT boost for prostate cancer yields similar results in terms of biochemical control and late toxicity compared with two or three-fraction schemes. Single fraction HDR-BT appears acceptable for boosting prostate cancer after definitive EBRT.

Glioblastoma is one of the most common types of primary brain tumor. In situations of local recurrence, physicians can suggest either specific palliative anticancer treatments (SPAT; surgery, chemotherapy, radiotherapy) or best supportive care (BSC). The objective of the present study was to identify clinical factors that may have influenced the continuation or cessation of SPAT during the final 3 months of life in patients with glioblastoma. In the present retrospective single-center study, all records of patients treated for glioblastoma, who succumbed to the disease between June 2006 and February 2014, were assessed. All selected patients were divided into two groups, according to treatments received during the last 3 months of life: The SPAT and BSC groups. A total of 148 patients were included: 81 patients in the SPAT group (group A) and 67 patients in the BSC group (group B). A performance status equal to 0 was observed for 17.3% of patients in group A vs. 6% in group B. Following progression, chemotherapy was administered in 39.5% of cases in group A vs. 20.9% of cases in group B (P=0.0149). The mean number of lines of chemotherapy administered in group A was equal to 1.44±0.77 as compared with 1.06±0.67 in group B (P=0.0017). SPAT are utilized frequently among patients approaching mortality due to a glioblastoma. Certain factors, including the utilization of novel chemotherapy after the first progression or number of lines of chemotherapy previously administered, may have influenced physicians' decisions whether to continue with the SPAT or not.

Introduction: Hepatocholangiocarcinoma (HCC-ICC) is a rare tumor presenting the histologic characteristics of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). As there is no consensus on it management, the therapeutic strategy rests on the specific treatments for HCC or ICC. Programmed cell death 1 (PD-1) inhibitors showed encouraging results in the second line treatment of HCC after sorafenib but it efficacy in HCC-ICC has never been reported. Methods and results: We present the case of a 72-year-old male patient treated for metastatic HCC-ICC due to a viral hepatitis C cirrhosis in progression after two lines of treatment. Tumor was characterized by a PDL-1 status of 85%. Patient received pembrolizumab at doses of 200 mg every 21 days by intravenous infusion. After one injection he was presented an immediate clinical benefit, a partial response was observed after two months of treatment and a complete response two months later. This response was maintained over time along with toxicity-free tumor control after 18 months treatment. Conclusion: To our knowledge, we reported for the first time the efficacy of a PD1 inhibitor treatment in a patient presenting metastatic HCC-ICC due to viral cirrhosis and overexpressing PDL-1 after failure of two lines of treatment.

Squamous cell carcinomas of the upper aerodigestive tract or head and neck cancers, are localized in a complex anatomical region with a major lymphohilic locoregional cervical extension. Cervical lymph node surgery is systematized and drainage areas are sectorized with an increasingly conservative attitude. Improving imaging techniques allow the realization of selective neck dissection; sentinel node techniques are being evaluated. The traditional dissection is reserved to the lymph in capsular rupture or cervical interstitial mass.

The purpose of new radiotherapy techniques is to better deliver dose conformation in the tumour volume while diminishing organs at risk exposition. Their development is soaring in the breast cancer field in the adjuvant setting with intensity-modulated radiation therapy but also in cerebral and extracerebral oligometastastic presentation. Their usage is still being debated for breast cancer care. The objective of this narrative review is to list and discuss clinical data at our disposal for these news technologies.

In clinical practice and the literature, malignant melanoma usually appears in typical sites where melanocytes can be found: skin, eyes meninges and anal region. Malignant melanomas of the esophagus-gastrointestinal (EGI) tract are usually metastatic. Primary and diffuse EGI tract melanoma is rare and only a few descriptions of this presentation have been found in the literature. The prognosis of EGI tract melanoma is frightening because of late diagnosis and high malignancy potential. Treatment is based essentially on surgery. The objective of the present study is to specify the clinical and therapeutic aspects of primary digestive melanoma.

There are only scarce data on the management of nonagenarians with breast cancer, and more particularly on the place of radiation therapy (RT). We report a retrospective study on patients aged 90 years old or older, with breast cancer, receiving RT. Records from RT departments from five institutions were reviewed to identify patients 90 years old of age and older undergoing RT over past decade for breast cancer. Tumors' characteristics were examined, as well treatment specificities and treatment intent. 44 patients receiving RT courses were identified, mean age 92 years. Treatment was given with curative and palliative intent in 72.7% and 27.3% respectively. Factors associated with a curative treatment were performance status (PS), place of life, previous surgery, and tumor stage. Median total prescribed dose was 40 Gy (23–66). Hypo fractionation was used in 77%. Most toxicities were mild to moderate. RT could not be completed in 1 patient (2.3%). No long-term toxicity was reported. Among 31 patients analyzable for effectiveness, 24 patients (77.4%) had their diseased controlled until last follow-up, including 17 patients (54.8%) experiencing complete response. At last follow-up, 4 patients (12.9%) were deceased, cancer being cause of death for two of them. The study shows that breast/chest RT is feasible in nonagenarians. Although the definitive benefit of RT could not be addressed here, hypofractionated therapy allowed a good local control with acceptable side effects.

Information concerning management of anal canal cancer among the elderly is scarce and much less abundant than for younger subjects.We retrospectively analysed 115 patients treated for anal epidermoid cancer between 2000 and 2010. The population was divided according to age (70 years and ≥70 years).Of the 115 patients, 81 (70.4%) were70 years old and 34 were ≥70 years (29.6%). Tumour characteristics were identical between the two groups and median follow-up was 62 months. Elderly patients had a less favourable performance status (p=0.001) and fewer had received radiochemotherapy (61.8% vs 82.5%, p=0.004). Treatment-related grade 3 and 4 hematologic toxicity was observed more often among elderly subjects. The results at 5 years were less favourable for overall, disease-specific, and disease-free survival (respectively p=0.002, p=0.001, and p=0.001). For patients treated with a curative intent, at 5 years there was no difference between the two groups in terms of overall survival (p=0.2). However, there was a statistically significant difference in favour of the younger group for disease-free survival and metastasis-free survival.If radiochemotherapy can be delivered to elderly subjects with a good general status, the effects appear less favourable than in younger patients.

Introduction et but de l’etude Des donnees cliniques et precliniques suggerent un benefice de l’association d’irradiation et d’inhibiteurs de checkpoint de l’immunite (de PD1 ou CTLA4). Le meilleur schema d’irradiation reste a determiner. Le but de cette etude etait d’analyser l’impact de l’irradiation sur la survie des patients pris en charge pour un carcinome bronchique non a petites cellules ou un melanome evolue. Materiel et methodes Cinquante-huit patients ont ete inclus. Ils etaient traites par inhibiteurs de checkpoint de l’immunite, avec une irradiation au cours du traitement ou a la progression prendant le traitement (a visee abscopale). Outre les facteurs classiques, une analyse de correlation avec la survie sans progression ou de survie globale a aussi ete faite avec les parametres de radioterapie suivants : nombre de cibles traitees, nombre d’organes, volume total irradie, dose par seance, dose totale, sequence du traitement par inhibiteurs de checkpoint de l’immunite/radiotherapie, type de cible irradiee, radiotherapie de toutes les cibles ou pas. Resultats et analyse statistique Trente-sept patients etaient atteints de melanome, 21 d’un cancer bronchique non a petites cellules ; en tout 119 cibles ont ete irradiees, 26 patients ont recu une radiotherapie concomitante a l’ inhibiteurs de checkpoint de l’immunite, 32 a visee abscopale, apres progression sous inhibiteurs de checkpoint de l’immunite. Il n’y avait pas de difference de survie sans progression ni de survie globale entre les patients irradies en meme temps ou a visee abscopale. En analyse multifactorielle, les facteurs de meilleure probabilite de survie sans progression etaient : la radiotherapie pulmonaire, l’histologie de melanome, le statut oligometastatique, le nombre de polynucleaires neutrophiles inferieur a 7000/mm3 et la concentration normale de lactate deshydrogenase (LDH). En analyse multifactorielle, les facteurs independants de survie globale etaient l’histologie de melanome et la concentration normale de LDH. Parmi les patients irradies au moment de la progression tumorale sous inhibiteurs de checkpoint de l’immunite, le maintien de l’inhibiteur a ete possible chez 19 des 32 patients (59,4 %), et ce pendant une moyenne de 70 jours (extremes : 0-874 jours). Deux effets abscopaux ont ete observes parmi les 21 patients traites “a visee” abscopale (et evaluables dans cette situation). Conclusion La radiotherapie d’une cible pulmonaire sous inhibiteur de checkpoint de l’immunite pourrait allonger la survie sans progression des patients atteints de cancer bronchique non a petites celllules ou de melanome. La neutrophilie est confirmee comme facteur defavorable dans cette association. Une irradiation a “visee abscopale” a permis de prolonger la duree de l’inhibiteur de checkpoint de l’immunite chez la plupart des patients.

Radiotherapy for epithelioid hemangioendothelioma (EHE) using volumetric intensity-modulated arc radiotherapy (VMAT). A 48-year-old woman was referred for curative irradiation of a vertebral EHE after failure of surgery. A comparison between VMAT and conventional conformal tridimensional (3D) dosimetry was performed and potential advantage of VMAT for sparing critical organs from irradiation׳s side effects was discussed. The total delivered dose on the planning target volume was 54 Gy in 27 fractions. The patient was finally treated with VMAT. The tolerance was excellent. There was no acute toxicity, including no increase in pain. With a follow-up of 18 months, no delayed toxicity was reported. The clinical response consisted of a decrease in the dorsal pain. The Dmax for the spinal cord was reduced from 55 Gy (3D-radiotherapy [RT]) (which would be an unacceptable dose to the spine because of the risk of myelopathy) to 42.8 Gy (VMAT), which remains below the recommended dose threshold (45 Gy). The dose delivered to 20% of organ volume (D20) was reduced from 47 Gy (3D-RT) to 3 Gy (VMAT) for the spinal cord. The study shows that VMAT allows the delivery of curative treatment for vertebral EHEs because of critical organ sparing.

Concomitant radiotherapy and cetuximab association has shown superiority to exclusive radiotherapy for head and neck cancers. Data on this association are scarce for the elderly population despite its rising incidence. A retrospective monocentric data collection was performed in the Antoine Lacassagne Cancer Center in France. Inclusion criteria were: age >70 years at time of diagnosis, histologically proven head and neck epidermoid carcinoma, treated with radiotherapy combined with cetuximab. Thirty-five patients were included between 2008 and 2012. Median follow-up was 22 months. Median age was 74 years (70–86). Median performance status was 1 (0–2). Female/male sex ratio was 0.34. Tumor sites were: oropharynx (57.1 %), larynx (20 %), hypopharynx (14.3 %), oral cavity (2.9 %), nasopharynx (2.9 %), and lymph node with unknown primary (2.9 %). Using TNM classification, tumors were: T1 (5.9 %), T2 (35.3 %), T3 (35.3 %), T4 (22.9 %), N0 (28.6 %), N1 (8.6 %), N2 (48.6 %), and N3 (14.3 %). Median radiotherapy dose was 70 (60–70). RT was interrupted in 94 % of patients and the dose of cetuximab was reduced in 29 %. Median survivals were, respectively: 49 months for overall survival (standard error (SE) = 8) and 32 months for relapse-free survival (SE = 10). Two-year local–regional relapse and metastatic relapse-free survivals were, respectively, 59 % (SE = 10) and 74 % (SE = 10). Concomitant radiotherapy and cetuximab seem to be an effective therapy in the elderly population with encouraging results similar to the literature concerning its efficacy and toxicity. This treatment should be considered for patients >70 years.

PD-1/PD-L1 inhibitors demonstrated durable clinical responses in patients with lung squamous cell carcinoma. However, the expression pattern of PD-L1 and the presence of CD8

Pulsed-dose-rate (PDR) brachytherapy is a recent brachytherapy modality combining the radiobiological advantages of low-dose-rate (LDR) brachytherapy with increased possibilities of dose optimization and radiation safety. However, treatment duration remains protracted, as the prescribed dose is typically delivered through pulses that do not exceed 0.5 Gy/h for critical organs. It is frequently used for the treatment of gynaecological malignancies. Although, the relationship between thrombosis and cancer is well known, specific data on thromboembolic events during brachytherapy are scarce. We report two cases of major thromboembolic events during brachytherapy treatment for gynaecological malignancies. We discuss the possible causal relationship between brachytherapy procedures and the occurrence of thromboembolic events, drawing a preventive practical attitude.

Objectif de l’etude La curietherapie des cancers de prostate apres radiotherapie externe permet d’escalader la dose pour ameliorer le taux de controle local. Pour la curietherapie interstitielle de haut debit de dose, le fractionnement optimal reste inconnu. L’objectif etait d’evaluer l’efficacite et la toxicite de trois schemas therapeutiques de curietherapie interstitielle de haut debit de dose pour des cancers de la prostate localises. Materiel et methode Nous avons realise une etude retrospective monocentrique au centre Antoine-Lacassagne, Nice, France. Les patients ont ete traites par irradiation externe puis ont recu une surimpression par curietherapie interstitielle de haut debit de dose de trois seances de 6 Gy, deux de 9 Gy ou une de 14 Gy. Les aiguilles ont ete inserees sous anesthesie generale et controle echographique. La scanographie dosimetrique et le traitement ont ete realises en situation postoperatoire. Resultats Un total de 159 dossiers de patients pris en charge entre 2009 et 2012 ont ete analyses. Neuf cancers (5,7 %) etaient de risque bas, 32 (20,1 %) de risque intermediaire et 118 (74,2 %) de haut risque sans difference significative entre les schemas de curietherapie. Le suivi median etait de 61 mois. Les probabilites de survies a 5 ans etaient de 86,6 % (erreur standard [ES] : 2,7 %), 98,3 % (ES : 1 %), 95,3 % (ES 1 %) et 96,5 % (ES : 1 %) respectivement pour la survie sans recidive biochimique, la survie sans recidive locale, la survie sans recidive metastatique et la survie globale, sans difference significative entre les differents schemas de curietherapie. Les taux de toxicite aigue genito-urinaires de grade 2 ou plus et gastro-intestinales de grade 2 ou plus etaient respectivement de 11,3 % et 9,4 %, sans difference significative entre les schemas. Les taux de toxicite tardive genito-urinaire et gastro-intestinale de grade 2 ou plus etaient respectivement de 9,4 % et 0,6 %, avec 0,6 % et 0 % de cas de toxicite de grade 4, sans difference significative entre les schemas de curietherapie. Conclusion La seance unique de curietherapie interstitielle de haut debit de dose apres une radiotherapie externe pour le cancer de la prostate permet d’obtenir des resultats equivalents en termes de controle biochimique et toxicite tardive compare aux schemas bi- ou trifractionnes. Afin de limiter la duree d’hospitalisation du patient et pour minimiser les couts, la seance unique pourrait etre proposee pour le complement d’irradiation.

Objectif de l’etude La curietherapie en boost est proposee comme une technique de choix pour les cancers de la prostate de risques intermediaire et defavorable dans beaucoup d’etudes retrospectives et prospectives. Actuellement, trois essais randomises comparent la curietherapie et la radiotherapie externe, mais avec des differences de techniques, de doses, de fractionnement et de duree d’hormonotherapie. Ainsi, nous avons realise une meta-analyse des essais randomises pour analyser les resultats carcinologiques. Materiel et methode Il a ete fait une revue systematique des bases de donnees Medline et Cochrane jusqu’au 30/4/18 et seuls les essais randomises comparant la curietherapie et la radiotherapie externe en boost ont ete inclus pour une analyse selon PRISMA (Preferred reporting items for systematic review and meta-analysis). La qualite de la revue a ete evaluee selon AMSTAR (Assessing the methodological quality of systematic reviews) et les articles individuels selon CONSORT (Consolidated standards of reporting trials). Huit articles sur les trois essais randomises ont ete analyses. Resultats Il y avait une difference significative de rechutes biochimiques en faveur de la curietherapie hazard ratio [HR] : 0,49 ; intervalle de confiance a 95 %[IC 95 %] : 0,37–0,66 ; p Conclusion Cette meta-analyse apporte un niveau de preuve supplementaire en faveur de la curietherapie en boost pour les cancers de la prostate de risques intermediaire et defavorable, pouvant la proposer en niveau de preuve 1 et grade de recommandation A. En revanche, l’analyse de la toxicite doit etre evaluee avec prudence.

Objectif de l’etude Evaluer l’efficacite et la toxicite d’une curietherapie de haut debit de dose de complement dans les carcinomes epidermoides du canal anal. Materiel et methode Etude retrospective monocentrique portant chez des patients traites par irradiation externe (avec ou sans chimiotherapie), avec complement de curietherapie de haut debit de dose, pour un carcinome epidermoide du canal anal localise. La surveillance clinique a ete realisee tous les six mois. Les resultats oncologiques sont analyses avec : les survies sans recidive locale, sans colostomie, sans metastase, sans evenement et globale. La toxicite aigue et tardive a ete recueillie (Common Terminology Criteria for Adverse Events V4.0). Resultats De mai 2005 a janvier 2018, 46 patients ont ete traites. La mediane de suivi etait de 61 mois (extremes : 10–145 mois), l’âge median de 65 ans (extremes : 34–84 ans) avec une sex-ratio hommes/femmes de 0,24. Il s’agissait de 13 tumeurs de stade T1 (21,7 %), 34 T2 (73,9 %), deux T3 (4,3 %), six N+ (13,1 %). La radiotherapie externe a delivre a une dose mediane de 45 Gy (extremes : 36–52 Gy) en 25 fractions et la curietherapie de haut debit de dose de 12 Gy (extremes : 10–18 Gy) en trois fractions. L’etalement median etait de 58 jours (extremes : 41–101 j) avec un intervalle median entre la radiotherapie externe et la curietherapie de 17 jours (extremes : 4–60 j). L’analyse des resultats carcinologiques a montre des taux a 5 ans de survie sans recidive locale de 81,2 %, de survie sans maladie de 88,7 %, de survie sans evenement de 70 % et de survie globale de 90 %. Toutes les amputations abdominoperineales ont ete realisees en cas de rechute locale (quatre patients, 8,7 %) conduisant a un taux de survie sans colostomie a 5 ans de 79,5 %. La toxicite urinaire aigue etait frequente (grade 1 : 41,3 % ; grade 2 : 4,3 %). La toxicite digestive aigue etait : grade 1 : 71,7 % ; grade 2 : 6,5 % ; grade 3 : 2,2 %. La toxicite urinaire tardive etait : grade 1 : 4,3 % ; grade 2 : 2,2 % ; grade 4 : 2,2 %. La toxicite digestive tardive etait : grade 1 : 56,5 % ; grade 2 : 8,7 % ; grade 3 : 2,2 % ; grade 4 : 2,2 %. Conclusion Dans la prise en charge du carcinome du canal anal, le complement par curietherapie de haut debit de dose semble etre un traitement presentant un profil de toxicite acceptable sur le long terme, plus court qu’un complement de radiotherapie externe avec une irradiation partielle du canal anal.

The aim of this study was to report the first cases of salvage radiotherapy (RT) using the intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) targeted on choline positron emission tomography (PET) uptake in a local recurrent prostate cancer, after a radical prostatectomy.Four patients received salvage irradiation for biochemical relapse that occurred after the initial radical prostatectomy. The relapse occurred from 10 months to 6 years with PSA levels ranging from 2.35 to 4.86 ng ml(-1). For each patient, an (18)F-choline PET-CT showed a focal choline uptake in prostatic fossa, with standardized uptake value calculated on the basis of predicted lean body mass (SUL) max of 3.3-6.8. No involved lymph node or distant metastases were diagnosed. IMRT doses were of 62.7 Gy (1.9 Gy/fraction, 33 fractions), with a SIB of 69.3 Gy (2.1 Gy/fraction, 33 fractions) to a PET-guided target volume.Acute toxicities were limited. We observed no gastrointestinal toxicity ≥grade 2 and only one grade 2 genitourinary toxicity. At 1-month follow-up evaluation, no complication and a decrease in PSA level (6.8-43.8% of the pre-therapeutic level) were reported. After 4 months, a decrease in PSA level was obtained for all the patients, ranging from 30% to 70%. At a median follow-up of 15 months, PSA level was controlled for all the patients, but one of them experienced a distant lymph node recurrence.Salvage irradiation to the prostate bed with SIB guided by PET-CT is feasible, with biological efficacy and no major acute toxicity.IMRT with PET-oriented SIB for salvage treatment of prostate cancer is possible, without major acute toxicity.

Objectives: Glioblastoma is one of the most frequent primitive brain tumors. Patients who experience tumor relapse after surgery and concomitant radiochemotherapy have a dismal prognosis. The objective of this study is to analyze efficacy data in terms of overall survival (OS) and progression- free survival (PFS) following combination therapy with bevacizumab (BVZ) and irinotecan among patients with relapsed glioblastoma. Safety data will also be reviewed and all results will be compared with data of the literature. Methods: In this single-center retrospective study, all records of patients treated with BVZ and irinotecan for a relapsed glioblastoma were analyzed. Each chemotherapy cycle was repeated every 15 days until progression. Magnetic resonance imaging and neurologic examination were repeated every 6 weeks during treatment. Results: Forty-five patients were analyzed. The median number of BVZ-irinotecan cycles was 8 (range 1-38). Median PFS was 26 weeks and median OS was 28 weeks. Eighteen of the 45 patients (40% of cases) had an objective response 6 months after initiation of treatment. Two patients had to discontinue treatment due to toxicity. Conclusions: The results of the SV1 study are consistent with those found in phase II studies evaluating the same treatment. The irinotecan-BVZ combination is effective in relapsed glioblastoma with acceptable toxicity. Biomarkers predictive of response to BVZ should help in the selection of patients who could benefit from treatment.

Background: We studied the efficacy and safety of cabazitaxel in unselected real-life patients. Patients and Methods: We retrospectively investigated all patients with metastatic prostate cancer (mPC) treated with cabazitaxel 25 mg/m2 i.v. every 3 weeks combined with oral prednisolone (10 mg once daily) after first-line docetaxel chemotherapy. Study issues were to report patient characteristics and cabazitaxel data in terms of tolerance and efficacy. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method. All data were compared with TROPIC results. Results: From 2011 to 2014, 41 patients received cabazitaxel; 15 patients (37%) had a performance status (PS) ≥2 versus 7% (p < 0.0001) in TROPIC, and 38 patients (93%) presented a Gleason score ≥7 at baseline (vs. 60%; p < 0.0001). All patients had metastatic disease at baseline. Previous therapies were radiotherapy in 17 patients (41 vs. 61%; p = 0.01) and surgery in 24 patients (59 vs. 52%; p = 0.4). The median number of cabazitaxel cycles was 5 (1-10) versus 6 (3-10) in TROPIC. Five patients completed 10 cycles of cabazitaxel (12%) versus 28% in TROPIC (p = 0.03). Toxicities were anemia (12 patients, 29%), diarrhea (9 patients, 22%), nausea (7 patients, 17%), pain (6 patients, 15%), sepsis (4 patients, 10%), neutropenia (3 patients, 7%) and urinary tract infection (1 patient, 2%). The tumor response rate was 19.5 versus 14.4% in TROPIC (nonsignificant). PFS was 4.5 months (95% CI 3.3-6.4) in our analysis and 2.8 months (95% CI 2.4-3.0) in TROPIC. OS was 12.1 months (95% CI 9.2 to not reached) and 15.1 months (95% CI 14.1-16.3), respectively. Conclusion: In our unselected mPC patients with poorer baseline clinical conditions and aggressive disease, cabazitaxel seems efficient and not more toxic than in the TROPIC study.

We retrospectively assessed the outcome of patients receiving emergency spinal radiation therapy (RT) concurrently with bevacizumab. Clinical records of 18 consecutive patients receiving emergency spinal RT for symptomatic vertebral metastases during the course of bevacizumab-based therapy were examined. Patients were receiving biweekly bevacizumab combined with paclitaxel (n=17) or with docetaxel/carboplatin (n=1) or as a single agent (n=1) for advanced metastatic carcinoma. RT was delivered at doses of 30 Gy in 10 fractions (n=8), 20 Gy in five fractions (n=9) or 18 Gy in nine fractions (n=1). In 10 patients (56%), irradiation field encompassed the thoracic vertebrae. The median time interval between the bevacizumab infusion and the RT course was 1.5 days (0-8 days). The median follow-up was 8.3 months (2 days-42 months). A clinical benefit of RT was reported in 13 patients (72%), including four patients with complete pain relief. Two of the three patients with neurological impairment at the time of RT experienced a partial improvement in their symptoms. No pain recrudescence was reported within the irradiated field after RT completion. All toxicities were mild to moderate, with no acute toxicity reported in 13 patients (72%). No RT disruption was necessary because of acute toxicity. No delayed toxicity was reported within RT fields among 11 patients with at least 6 months of follow-up. Spinal RT during the course of bevacizumab-based therapy was not associated with the occurrence of unexpected adverse effects. This suggests that emergency RT should not be contraindicated in these patients, provided that doses and treatment volumes are defined carefully.

Summary The number of nonagenarian people in the world is steadily growing. This phenomenon will increase in future years: in 2050, world population prospects estimate 71.16 million people aged 90 years or older. The two main causes of death among people aged 85 years or more in Europe in 2003 were cardiovascular and cerebrovascular diseases and cancers. However, the elderly are often excluded from clinical trials; they are underrepresented in clinical registries and especially nonagenarians. Care (medical, surgical, oncology) of these very elderly is currently insufficiently based on scientific recommendations. For the physician, the choice to treat or not to treat very elderly patients (for fear of side effects) is difficult. Oncology is particularly affected by this problem. Here we review these different fields of internal medicine management of nonagenarian patients with a special focus on oncology and on comprehensive geriatric assessment as a base for all care decision taking.

We report the case of an 80-year-old patient who presented with a progressive prostate metastatic cancer with poor performance status. The patient had already benefitted from docetaxel and abiraterone. A new line of chemotherapy by cabazitaxel was started with good response, and there was a dramatic improvement in general status and pain symptoms. Age and performance status alone should not be limiting decision factors for elderly cancer patients.

The aim of the study was to analyze the medical and economic interest of OSNA molecular technique, compared to conventional postoperative histopathologic evaluation for sentinel lymph node exploration in breast cancer patients. This retrospective cost-benefit study was conducted in the French Universitary Hospital of Saint Etienne on patients who received sentinel lymph node exploration between July 1, 2007 and December 31, 2009. Lymph nodes were analyzed by conventional postoperative histological evaluation in group 1 (82 patients) and OSNA in group 2 (86 patients). Costs were analyzed in three different ways: surgery cost, hospitalization cost and histopathologic cost. Average operating time was slightly shorter for group 1 (histology) [71.9 vs. 76.8 min for group 2 (OSNA)]. Time and operating costs were not significantly different (p = 0.293). The average cost of pathological examination was significantly higher in group 2 (35.04 euros per node in group 1 vs. 291.84 euros per node in group 2 p

International audience; Head and neck squamous cell carcinomas (HNSCC) represent a multifactorial disease of poor prognosis. They have lagged behind other cancers in terms of personalized therapy. With expansion and high throughput sequencing methods, recent landmark exonic studies and Cancer Genome Atlas data have identified genes relevant to carcinogenesis and cancer progression. Mutational profiles and rates vary widely depending on exposure to carcinogens, anatomic subsites and human papilloma virus (HPV) infection. Tumors may exhibit specific, tissue-specific, not exclusively HPV-related, gene alterations, such those observed in oral cavity cancers in Asia or Occident. Except for the PI3K pathway, the rate of mutations in HPV+ cancers is much lower than in tobacco/alcohol-related cancers. Somatic driver mutation analyses show that relatively few driver genes are druggable in HNSCC and that tumor suppressor gene alterations prevail. More mature for therapeutic applications is the oncogenic PI3K pathway, with preclinical human xenograft models suggesting that PI3KCA pathway mutations may be used as predictive biomarkers and clinical data showing efficacy of mTOR/Akt inhibitors. Therapeutic guidance, to date, relies on classical histoprognostic factors, anatomic subsite and HPV status, with integration of hierarchized supervised mutational profiling to provide additional therapeutic options in advanced HNSCC in a near future. Unsupervised controlled genomic analyses remain necessary to unravel potentially relevant genes.

Glioblastoma multiform is the most common and aggressive brain tumor with a worse prognostic. Ionizing radiation is a cornerstone in the treatment of glioblastome with chemo-radiation association being the actual standard. As a paradoxal effect, it has been suggested that radiotherapy could have a deleterious effect on local recurrence of cancer. In vivo studies have studied the effect of radiotherapy on biological modification and pathogenous effect of cancer cells. It seems that ionizing radiations with photon could activate oncogenic pathways in glioblastoma cell lines. We realized a review of the literature of photon-enhanced effect on invasion and migration of glioblastoma cells by radiotherapy.

Purpose The mainstay of first line treatment in metastatic sarcomas is chemotherapy with response rates of ≈25% but the optimal management of further events is debated. We assessed the benefit of local metastatic treatment in metastatic sarcomas. Results Local control of local treatment strategies (≈85%) is excellent but highly institution-dependent and subject to selection biases. Formal evidence of an improvement of survival with local ablative treatments has been limited to retrospective studies. On the other hand, some chemotherapy trials are inconclusive because about 20% of patients receive local metastatic ablation as it is considered unethical to omit local treatment in these patients. Further, technology has made surgery, stereotactic irradiation and radiofrequency ablation highly effective on local control with limited morbidity. Conclusion The benefit on survival of metastatic ablation deserves prospective studies integrating quality of life, cost effectiveness and patient-reported outcomes assessment.