This review updates the radiotherapy indications for non-malignant diseases, except those treated by radiosurgery. Since the last 2005 review, there have been no major changes in the indications: the prevention of heteropic bone formation and keloids remain classical indications, while the treatment of macular degeneration or the prevention of coronary restenosis are now past history. Nevertheless, the radiation treatment for benign diseases should have the same criteria as for malignant diseases: information of the patient on risks, benefits and treatment quality.

Our purpose was to provide a state-of-the-art regarding the different non-surgical treatment modalities available for urologists in the modern management of upper urinary tract carcinoma (UTUC).

Ferroptosis is a form of cell death that has recently been reported during exposure to erastin, a chemical compound identified in a screen for molecules able to kill cancer cells carrying an active Ras oncogene. In cells exposed to inducers of ferroptosis, a catastrophic alteration of the cellular redox metabolism occurs, resulting in massive lipid peroxidation in the plasma membrane and loss of cell viability. We present our recent observations suggesting that sorafenib, the only medical treatment with proven efficacy against hepatocellular carcinoma, induces ferroptosis, a new anti-oncogenic mode of action of this drug. The discovery of ferroptosis sheds light on the critical adaptations of the redox metabolism in cancer cells. It might also foster the discovery of new biomarkers and innovative approaches for the treatment of cancer.

Secondary localization to vagina had a severe prognosis, suggesting a disseminated metatastic disease. We report the case of prevalent vaginal metastasis of adenocarcinoma of the transverse colon. A 65 years old patient has consulted for vaginal mass. After delayed diagnosis, she presented with disseminated metastatic disease with peritoneal carcinomatosis. After neoadjuvant chemotherapy, the following treatment consisted of complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy and vaginal adjuvant radiotherapy. No recurrence occurred after one year. Vaginal metastasis of colon cancer are rare. The dark prognosis might justify a systematic gynecological examination of women presenting colorectal neoplasy.

Autoimmune diseases may reveal or occur during the course of a neoplasia or its treatment. Autoimmune cytopenia, especially haemolytic anaemia, is common in lymphoproliferative disorders such as chronic lymphoid leukemia. The link between cancer and myositis is well established. Dermatomyositis is associated with an increased relative risk of cancer of 3.4 to 4.4. A combination of detection of antibodies against p155 and TEP-computed tomography may be the best approach to ascertain the presence of occult malignancy in patients with dermatomyositis. A cutaneous or a systemic vascularitis may reveal a cancer, most often a haematological malignancy such as hairy cell leukemia. Paraneoplastic polyarthritis have been described in particular with adenocardinoma of the lungs. Underlying neoplasia should be considered in male smokers patients with new onset polyarthritis and poor health status. The prevalence of autoimmune conditions in myelodysplastic syndromes is 10 to 30%. Vasculitis and relapsing polychondritis are the most commonly reported manifestations. Immune manifestations can also be related to treatment. The most common treatment complications are autoimmune haemolytic anaemia with fludarabine and thyroiditis related to interferon and cervical radiotherapy.

Fifteen to 20% of breast cancers display HER2 amplification. Many therapeutic successes have been obtained for this subtype in the last decade since trastuzumab approval for metastatic and localized diseases. Pertuzumab, a new anti-HER2 antibody, has been approved in 2013 by the European Medicine Agency. This drug can be used in combination with trastuzumab and docetaxel for the first line treatment of metastatic or locally recurrent non resecable HER2-positive breast cancers not previously treated by chemotherapy or HER2-inhibitors in the metastatic setting. This approval has been done after the CLEOPATRA trial results. This was a randomized, double-blind, multicentre, phase III trial evaluating the standard treatment (trastuzumab plus docetaxel) associated to pertuzumab or placebo. The authors have reported a statistically significant and clinically relevant benefit for the pertuzumab-based treatment. Median progression-free survival was 18.4 for the pertuzumab arm versus 12.5 months for the control group (p<0.001). They also observed benefits concerning the secondary endpoints: overall response rate and overall survival. Patients receiving pertuzumab presented more frequent diarrhea and febrile neutropenia but no increase in cardiac events. This drug has already been evaluated in the neoadjuvant setting with a FDA approval recently obtained. Its use in the adjuvant setting is under evaluation.

There is an increasing number of therapeutic options in breast cancer management. While prognosis improves, the cardiac toxicity related to treatments remains a significant issue. This toxicity has several clinical presentations and can be explained by complex and diverse molecular mechanisms. Systemic treatments (anthracyclines, inhibitors of HER2 signaling pathway, hormone therapy, antiangiogenic agents) and radiotherapy have their own cardiac toxicity. However, the toxicities associated with these treatments may potentiate together and the existence of pre-existing cardiovascular risk factors should be taken into account. The assessment of cardiac hazard evolves toward a multifactorial approach. Several possibilities exist to minimize the incidence of cardiac complications. Those include pharmacological and technological innovations, but also a more accurate selection of patients and a growing involvement of practitioners in the field of cardiac toxicity, which is prerequisite for an early management of cardiac events.

This overview focuses on the follow up after uterine cervix and corpus cancers. At early stage, both are associated with good prognosis. Screening for recurrence is mainly based on clinical examination. Screening for a second cancer after endometrial cancer is already planned according to the French recommendations for systematic breast and colon cancer screening. Screening for a second cancer after cervical cancer requires a close examination of organs close to the cervix receiving high doses of radiations and HPV exposed (anus, vulva, vagina and perineum). Late chemotherapy related toxicity after both cancers is rarely encountered and mainly comprise neurological peripheral effects. Late surgical and/or radiation related side effects are more frequent. However, no more than 10% of patients are affected and in such cases, digestive, urinary and lymphatic systems are impaired. Prevalence of sexual dysfunction in patients with uterine cancers is particularly high but the radiotherapy related anatomical modifications (vaginal stenosis for example) might not be the sole reason. Fertility preservation is possible for uterine cancers but requires a rigorous selection of candidates and should be coordinated by specialized team.

In this retrospective study, the tolerance to subcutaneus mistletoe injections (Viscum album L.), adverse reactions and possible indications have been evaluated in feline patients of a small animal clinic. Among the 22 cats treated between 2008 and 2013, 4 did not accept the injections done by the owner, 7 showed slight short time adverse reactions, that disappeared spontaneously. No long term (more than 70 days) adverse reaction directly related to the Viscum album treatment could be identified. This study shows that Iscador(®) can be injected subcutaneously without a risk of worsening of the clinical signs or exacerbation of tumors. The antitumoral, but also immune-modulating and anti-inflammatory properties offer interesting treatment opportunities for dermatologic, odonto-stomatologic or allergic patients.

The evaluation of quality of life has become essential in gynecological oncology. Recent guidelines have been published to improve the collection, analysis and publication of the data quality of life that will make them more reliable, reproducible and integrate them into the final treatment decision. This year at ASCO, in breast cancer, the benefit of sentinel lymph node dissection compared to the quality of life has been demonstrated. New data on cognitive function in patients treated for breast cancer show the importance of the evaluation of these disorders especially among elderly patients who are at-risk populations. Medical strategies including targeted therapies can improve survival without impairing the quality of life, also with improved gastrointestinal symptoms in case of combination chemotherapy with bevacizumab in patients with ovarian cancer in a situation early recurrence. Similarly, the addition of a pathway inhibitor M- Tor (everolimus) with hormonal therapy does not induce degradation of the quality of life in women with metastatic breast cancer.

Tyrosine kinase inhibitors (TKI) that block epidermal growth factor receptor (EGFR) pathway have demonstrated a clinical benefit for patients with non-small-cell lung cancer (NSCLC) harboring EGFR mutations. The currently available TKI (gefitinib and erlotinib) are EGFR reversible inhibitors. Afatinib is an oral, irreversible ErbB family blocker that covalently binds and blocks signaling from EGFR (ErbB1), HER2 (ErbB2) and ErbB4. The compound inhibits also the transphosphorylation of ErbB3. With this mode of action, afatinib is thought to have a mechanistic advantage over EGFR blockade alone, in that it provides a sustained, covalent inhibition of ErbB homo- and hetero-dimers. In the pivotal LUX-Lung 3 study, afatinib demonstrated a prolonged progression free survival over standard pemetrexed plus cisplatin chemotherapy (11.1 versus 6.9 months; HR = 0.58, 95% CI: 0.43-0.78; P = 0.001) in EGFR mutation positive NSCLC patients. The compound has recently been granted a marketing authorization (MA) for the treatment of patients with locally advanced or metastatic NSCLC with activating EGFR mutation(s) and EGFR TKI-naive. In this paper are summarized the efficacy and safety data in this indication.

The role of angiogenesis in the physiopathology of renal cell carcinoma is fundamental. Strategies targeting angiogenesis have been developed including VEGF and VEGFR inhibitors for the treatment of metastatic renal cell carcinoma (mRCC), in first and second line. Pazopanib is an angiogenesis inhibitor targeting VEGF receptor, PDGF receptor and c-KIT receptor. This treatment is a treatment option recommended for patients with mRCC, would be in first line or after cytokines failure. Pazopanib has been recently approved for patients with metastatic soft tissue sarcoma, after failure of at least one line of chemotherapy.

Since 2006, new treatments as targeted therapies (anti angiogenic and mTOR inhibitors) are prescribed in renal cell cancer. Toxicity of these treatments is well known by clinicians. Occurrence of these side effects has been associated with anti tumoral efficacy. High blood pressure, hypothyroïdie and hand foot syndrome were reported to be predictive of anti tumoral response. Fatigue and hyponatremia are still largely discussed. Moreover, non infectious pneumonia, which frequently occurs with mTOR inhibitors, is associated with clinical benefit. The main objective of treatment of advanced kidney cancer, specially renal cell cancer, is obtaining clinical benefit (stabilization and response) with a chronic evolution of the disease. This prolong exposure to drugs, according to their toxicity profile, often contributes to dose reduction, moreover interruption of treatment, potentially associated with a loss of control of disease. Thus, the adverse effects, described hereby, may be considered as « positive events », predicting efficacy, and thus looked for… Moreover, the sequential approach, with new drugs, emphasizes the need of defining the optimal sequence. Thus, because of the lack of molecular biomarkers to date, this predictives secondary effects may help for selecting the therapeutic strategy.

Irinotecan is a cytotoxic agent administered by IV infusion in the treatment of advanced colorectal cancer. Its anticancer activity results from its bioactivation into SN-38 metabolite, which is cleared through glucuronidation by the hepatic enzyme uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1). In the general population, there is wide inter-subject variability in UGT1A1 enzyme activity related to UGT1A1 gene polymorphisms. The French joint workgroup coming from the National Pharmacogenetic Network (RNPGx) and the Group of Clinical Oncologic Pharmacology (GPCO) herein presents an updated review dealing with efficacy and toxicity clinical studies related to UGT1A1 genetic variants. From a critical analysis of this review it clearly emerges that, for doses higher than 180 mg/m(2), hematologic and digestive irinotecan-induced toxicities could be prevented in daily clinical practice by generalizing the use of a simple pharmacogenetic test before starting treatment. The clinical relevance of this test is also discussed in terms of treatment efficacy improvement, with the possibility of increasing the irinotecan dose in patients not bearing the deleterious allele. This test involves using a blood sample to analyze the promoter region of the UGT1A1 gene (UGT1A1*28 allele). Best execution practices, laboratory costs, as well as results interpretation are described with the aim of facilitating the implementation of this analysis in clinical routine. The existence of a French laboratories network performing this test in clinical routine makes it possible to generalize UGT1A1 deficiency screening, so as to guarantee equal access to safe treatment and optimized irinorecan-based therapy for the many patients receiving irinotecan-based therapy in advanced colorectal cancer.

To assess the prognostic value of clinical and biological variables in the era of targeted therapies, especially induced toxicity in patients treated for metastatic renal cell carcinoma (RCC).

Alopecia is a side effect of chemotherapies used in breast cancer. Scalp cooling is a technique preventing alopecia, but its use remains controversial. We conducted a survey about knowledge of scalp cooling and interest in conducting a randomized clinical trial (RCT). An invitation was sent to 1,022 participants and a total of 139 individuals responded to the survey. The majority knew about the existence of scalp cooling. Ninety per cent thought that an RCT was needed and would participate. The survey revealed different potential problems associated with the increased chair time, limited space, and safety. We concluded that an RCT is needed and that the trial must include evaluation on the impact on health care system resources and safety.