Cet article passe en revue les études précliniques concernant les effets non ciblés de la radiothérapie et les mécanismes biologiques impliqués

Radiation-induced bystander and abscopal effects: important lessons from preclinical models

Daguenet, Elisabeth ; Louati, Safa ; Wozny, Anne-Sophie ; Vial, Nicolas ; Gras, Mathilde ; Guy, Jean-Baptiste ; Vallard, Alexis ; Rodriguez-Lafrasse, Claire ; Magne, Nicolas

Radiotherapy is a pivotal component in the curative treatment of patients with localised cancer and isolated metastasis, as well as being used as a palliative strategy for patients with disseminated disease. The clinical efficacy of radiotherapy has traditionally been attributed to the local effects of ionising radiation, which induces cell death by directly and indirectly inducing DNA damage, but substantial work has uncovered an unexpected and dual relationship between tumour irradiation and [...]

Menée in vitro et à l'aide de modèles murins de cancer, cette étude met en évidence l'intérêt d'activer la voie de détection de l'ADN cytosolique "cGAS-STING" dans les lymphocytes T CD8+ pour améliorer l'efficacité des immunothérapies par transfert adoptif de lymphocytes T

cGAS-STING–mediated DNA sensing maintains CD8+ T cell stemness and promotes antitumor T cell therapy

Li, Wenwen ; Lu, Lu ; Lu, Juanjuan ; Wang, Xinran ; Yang, Chao ; Jin, Jingsi ; Wu, Lingling ; Hong, Xiaochuan ; Li, Fanlin ; Cao, Dongqing ; Yang, Yuanqin ; Wu, Meng ; Su, Bing ; Cheng, Jinke ; Yang, Xuanming ; Di, Wen ; Deng, Liufu

Stimulator of interferon genes (STING) agonism is an area of active exploration for cancer immunotherapy. Li et al. examined the cGAS-STING DNA sensing cascade in antitumor CD8+ T cells. They observed dampened STING activity in CD8+ T cells from patients with cancer or mice implanted with tumors. STING signaling supported a stem-like memory phenotype in the T cells, which is known to be beneficial for responses to immunotherapy. Cytosolic DNA was enriched in activated T cells, and STING agonism [...]

Menée sur des modèles murins et des macaques, cette étude met en évidence l'intérêt d'anticorps bispécifiques ciblant l'antigène CD28 pour augmenter l'efficacité antitumorale des anti-PD-1

Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy

Waite, Janelle C. ; Wang, Bei ; Haber, Lauric ; Hermann, Aynur ; Ullman, Erica ; Ye, Xuan ; Dudgeon, Drew ; Slim, Rabih ; Ajithdoss, Dharani K. ; Godin, Stephen J. ; Ramos, Ilyssa ; Wu, Qi ; Oswald, Erin ; Poon, Patrick ; Golubov, Jacquelynn ; Grote, Devon ; Stella, Jennifer ; Pawashe, Arpita ; Finney, Jennifer ; Herlihy, Evan ; Ahmed, Hassan ; Kamat, Vishal ; Dorvilliers, Amanda ; Navarro, Elizabeth ; Xiao, Jenny ; Kim, Julie ; Yang, Shao Ning ; Warsaw, Jacqueline ; Lett, Clarissa ; Canova, Lauren ; Schulenburg, Teresa ; Foster, Randi ; Krueger, Pamela ; Garnova, Elena ; Rafique, Ashique ; Babb, Robert ; Chen, Gang ; Stokes Oristian, Nicole ; Siao, Chia-Jen ; Daly, Christopher ; Gurer, Cagan ; Martin, Joel ; Macdonald, Lynn ; MacDonald, Douglas ; Poueymirou, William ; Smith, Eric ; Lowy, Israel ; Thurston, Gavin ; Olson, William ; Lin, John C. ; Sleeman, Matthew A. ; Yancopoulos, George D. ; Murphy, Andrew J. ; Skokos, Dimitris

Although immunotherapy has been achieving increasing prominence in cancer treatment, these methods are not perfect, and many tumors still do not respond to treatment. One approach used for cancer immunotherapy is bispecific antibodies, which recognize a receptor on the surface of T cells and a tumor antigen, helping to bring the two types of cells together and activate the T cells. Building on recent advances in this field, Waite et al. used bispecific antibodies targeting CD28 on T cells and [...]

Menée notamment à l'aide de modèles murins, cette étude démontre que le récepteur leurre IL-18BP, sécrété par les cellules mononuclées, constitue un point de contrôle immunitaire et limite l'activité antitumorale de l'interleukine IL-18

IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy

Zhou, Ting ; Damsky, William ; Weizman, Orr-El ; McGeary, Meaghan K. ; Hartmann, K. Patricia ; Rosen, Connor E. ; Fischer, Suzanne ; Jackson, Ruaidhri ; Flavell, Richard A. ; Wang, Jun ; Sanmamed, Miguel F. ; Bosenberg, Marcus W. ; Ring, Aaron M.

Cytokines were the first modern immunotherapies to produce durable responses in patients with advanced cancer, but they have only modest efficacy and limited tolerability1,2. In an effort to identify alternative cytokine pathways for immunotherapy, we found that components of the interleukin-18 (IL-18) pathway are upregulated on tumour-infiltrating lymphocytes, suggesting that IL-18 therapy could enhance anti-tumour immunity. However, recombinant IL-18 previously did not demonstrate efficacy in [...]

Menée à l'aide de lignées cellulaires et d'un modèle murin de leucémie myéloïde, cette étude met en évidence l'intérêt d'un vaccin utilisant un peptide synthétique dérivé de la kinase PLK1 pour contourner l'hétérogénéité clonale du complexe majeur d'histocompatibilité des cellules leucémiques

An effective peptide vaccine strategy circumventing clonal MHC heterogeneity of murine myeloid leukaemia

Shin, A. Ri ; Lee, Sang-Eun ; Choi, Haeyoun ; Sohn, Hyun-Jung ; Cho, Hyun-Il ; Kim, Tai-Gyu

Background : Therapeutic cancer vaccines are an attractive approach for treating malignant tumours, and successful tumour eradication depends primarily on controlling tumour immunosuppression status as well as heterogeneity of tumour cells driven by epigenetic alterations. Methods : Peptide-loaded dendritic cell (DC) prime and non-infectious peptide booster heterologous immunisations were assessed for the immunogenicity of polo-like kinase-1 (PLK1)-derived peptides. Heterologous vaccination [...]

Menée à l'aide de lignées cellulaires et de xénogreffes de cancer du pancréas sur des modèles murins, cette étude met en évidence l'intérêt d'un traitement combinant inhibiteurs de CDK4/6 et MEK pour retarder la progression tumorale

Targeting dual signalling pathways in concert with immune checkpoints for the treatment of pancreatic cancer

Knudsen, Erik S. ; Kumarasamy, Vishnu ; Chung, Sejin ; Ruiz, Amanda ; Vail, Paris ; Tzetzo, Stephanie ; Wu, Jin ; Nambiar, Ram ; Sivinski, Jared ; Chauhan, Shailender S. ; Seshadri, Mukund ; Abrams, Scott I. ; Wang, Jianmin ; Witkiewicz, Agnieszka K.

Objective : This study exploits the intersection between molecular-targeted therapies and immune-checkpoint inhibition to define new means to treat pancreatic cancer. Design Patient-derived : cell lines and xenograft models were used to define the response to CDK4/6 and MEK inhibition in the tumour compartment. Impacts relative to immunotherapy were performed using subcutaneous and orthotopic syngeneic models. Single-cell RNA sequencing and multispectral imaging were employed to delineate [...]

Menée in vitro et à l'aide d'une xénogreffe de cancer de la prostate sur un modèle murin, cette étude met en évidence l'intérêt d'une stratégie thérapeutique consistant à cibler les sites d'épissage 5' et 3' de l'exon 4 de ERG (un oncogène codant pour un facteur de transcription de la famille ETS) à l'aide d'oligonucléotides synthétiques qui agissent comme des antisens

Targeting the ERG oncogene with splice-switching oligonucleotides as a novel therapeutic strategy in prostate cancer

Li, Ling ; Hobson, Lisa ; Perry, Laura ; Clark, Bethany ; Heavey, Susan ; Haider, Aiman ; Sridhar, Ashwin ; Shaw, Greg ; Kelly, John ; Freeman, Alex ; Wilson, Ian ; Whitaker, Hayley ; Nurmemmedov, Elmar ; Oltean, Sebastian ; Porazinski, Sean ; Ladomery, Michael

Background : The ERG oncogene, a member of the ETS family of transcription factor encoding genes, is a genetic driver of prostate cancer. It is activated through a fusion with the androgen-responsive TMPRSS2 promoter in 50% of cases. There is therefore significant interest in developing novel therapeutic agents that target ERG. We have taken an antisense approach and designed morpholino-based oligonucleotides that target ERG by inducing skipping of its constitutive exon 4. Methods : We designed [...]

Menée à l'aide d'un modèle murin de cancer mammaire avec métastases pulmonaires, de techniques d'imagerie et d'une modélisation mathématique, cette étude analyse le transport, la distribution intratumorale et les interactions d'une nanoparticule radiomarquée, composée de microparticules de silicone et chargée en doxorubicine

Sequential deconstruction of composite drug transport in metastatic breast cancer

Goel, Shreya ; Zhang, Guodong ; Dogra, Prashant ; Nizzero, Sara ; Cristini, Vittorio ; Wang, Zhihui ; Hu, Zhenhua ; Li, Zheng ; Liu, Xuewu ; Shen, Haifa ; Ferrari, Mauro

It is challenging to design effective drug delivery systems (DDS) that target metastatic breast cancers (MBC) because of lack of competent imaging and image analysis protocols that suitably capture the interactions between DDS and metastatic lesions. Here, we integrate high temporal resolution of in vivo whole-body PET-CT, ex vivo whole-organ optical imaging, high spatial resolution of confocal microscopy, and mathematical modeling, to systematically deconstruct the trafficking of injectable [...]

Mené sur 40 puis 24 patients atteints d’une tumeur solide, cet essai de phase I évalue la dose maximale tolérée et l’efficacité, du point de vue du taux de réponse objective, du mogamulizumab (un anticorps anti-CCR4) en combinaison avec le durvalumab ou le trémélimumab

Mogamulizumab in Combination with Durvalumab or Tremelimumab in Patients with Advanced Solid Tumors: a Phase I Study

Dmitriy Zamarin, Omid Hamid, Asha Nayak-Kapoor, Solmaz Sahebjam (et al.)

Purpose: The study goal was to determine safety, antitumor activity, and pharmacodynamic profile of mogamulizumab, an anti-CCR4 monoclonal antibody (mAb) targeting effector regulatory T cells (eTregs), in combination with mAb checkpoint inhibitors durvalumab or tremelimumab. Experimental Design: This was a multicenter, phase I, dose-escalation study, followed by disease specific cohort expansion (NCT02301130). Mogamulizumab dose escalation proceeded with concurrent dose escalation of durvalumab [...]

Mené aux Etats-Unis sur 46 patients atteints d’une tumeur solide de stade avancé, cet essai de phase I évalue la dose maximale tolérée du talétrectinib (un inhibiteur de ROS1/TRK) et analyse ses caractéristiques pharmacocinétiques

US phase 1 first-in-human study of taletrectinib (DS-6051b/AB-106), a ROS1/TRK inhibitor, in patients with advanced solid tumors

Kyriakos P. Papadopoulos, Erkut Borazanci, Alice T Shaw (et al.)

PURPOSE: Taletrectinib (DS-6051b/AB-106) is an oral, tyrosine kinase inhibitor of ROS1 and NTRK with potent pre-clinical activity against ROS1 G2032R solvent-front mutation among others. We report the first-in-human US-phase 1 results of taletrectinib. PATIENTS AND METHODS: Patients -18 years old with neuroendocrine tumors, with tumor-induced pain, or tumors harboring ROS1/NTRK rearrangements were eligible. Accelerated titration followed by modified continuous reassessment method and escalation [...]

Mené sur 184 patients atteints d’un myélome multiple (âge médian : 68 ans) et souffrant de néphropathie et de lésion rénale aiguë, cet essai randomisé compare l’intérêt, du point de vue du taux de réponse au niveau du rein, et la toxicité d’un doublet et d’un triplet à base de bortézomib

Randomized Trial Comparing Double Versus Triple Bortezomib-Based Regimen in Patients With Multiple Myeloma and Acute Kidney Injury Due to Cast Nephropathy

Frank Bridoux, Bertrand Arnulf, Lionel Karlin (et al.)

PURPOSE : We report a multicenter controlled trial comparing renal recovery and tolerance profile of doublet versus triplet bortezomib-based regimens in patients with initial myeloma cast nephropathy (CN) and acute kidney injury (AKI) without need for dialysis. METHODS : After symptomatic measures and high-dose dexamethasone, patients were randomly assigned to receive bortezomib plus dexamethasone (BD), or BD plus cyclophosphamide (C-BD). In patients with < 50% reduction of serum free light [...]

A partir d’une revue systématique de la littérature, cette étude présente des recommandations pour la prise en charge des effets indésirables induits par l’axitinib dispensé en combinaison avec un inhibiteur de points de contrôle immunitaire (pembrolizumab ou avélumab) en traitement de première ligne chez des patients atteints d'un cancer, notamment d’un carcinome à cellules rénales de stade avancé

Axitinib plus immune checkpoint inhibitor: evidence- and expert-based consensus recommendation for treatment optimisation and management of related adverse events

Viktor Grünwald, Martin H. Voss, Brian I. Rini, Thomas Powles (et al.)

With the recent approval of the combinations of axitinib with the immune checkpoint inhibitor (ICI) pembrolizumab or avelumab for first-line treatment of advanced renal cell carcinoma, guidance on how to distinguish between immune-related adverse events (AEs) caused by ICI versus axitinib-related AEs is necessary to optimise therapy with axitinib–ICI combinations. The recommendations here are based on (1) systematic review of published evidence, (2) discussion among experts in the field and (3) [...]

Mené en Espagne sur 166 patientes atteintes d’un cancer du sein HER2+ de stade métastatique, cet essai de phase III analyse leurs préférences concernant le mode d’administration du trastuzumab (voie sous-cutanée ou intraveineuse)

Phase III study to evaluate patient’s preference of subcutaneous versus intravenous trastuzumab in HER2-positive metastatic breast cancer patients: Results from the ChangHER study (GEICAM/2012-07)

Eva M. Ciruelos, Alvaro Montaño, César A. Rodríguez (et al.)

Objective : We compared patients’ preferences for intravenous (IV?t) versus subcutaneous (SC?t) trastuzumab administration. Methods : Phase III, open-label, multicentre study in HER2-positive metastatic breast cancer. Patients were receiving IV?t for at least 4 months without progression. Randomisation was 1:1 to administer 2 cycles of SC?t with vial followed by 2 cycles with single injection device (SID) or the reverse sequence (600mg SC?t every 3 weeks for 4 cycles). Primary objective: [...]

Mené sur des patientes atteintes d’un cancer métastatique du sein ERBB2+, cet essai de phase I/II évalue la dose maximale tolérée du trastuzumab emtansine, seul ou en combinaison avec la capécitabine, puis évalue son efficacité, du point de vue du taux de réponse objective

Efficacy and Safety of Trastuzumab Emtansine Plus Capecitabine vs Trastuzumab Emtansine Alone in Patients With Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer : A Phase 1 and Randomized Phase 2 Trial

Javier Cortés, Véronique Diéras, Sylvie Lorenzen (et al.)

Importance : ERBB2 (HER2)-targeted therapy provides benefits in metastatic breast cancer (mBC) and gastric cancer, but additional treatments are needed to maximize efficacy and quality of life. Objective : To determine maximum tolerated doses (MTDs) of trastuzumab emtansine (T-DM1) plus capecitabine in patients with previously treated ERBB2-positive mBC and locally advanced/metastatic gastric cancer (LA/mGC) (phase 1) and the efficacy and safety of this combination vs T-DM1 alone in patients [...]

Mené sur 184 patients atteints d’un cancer médullaire de la thyroïde symptomatique et de stade progressif, cet essai de phase III évalue l’efficacité, du point de vue de la survie sans progression, et la toxicité du vandétanib

Efficacy and Safety of Vandetanib in Progressive and Symptomatic Medullary Thyroid Cancer: Post Hoc Analysis From the ZETA Trial

Michael C. Kreissl, Lars Bastholt, Rossella Elisei (et al.)

PURPOSE : We conducted a post hoc analysis of the vandetanib phase III trial involving patients with advanced medullary thyroid cancer (MTC) to assess the efficacy and safety of vandetanib in patients with progressive and symptomatic MTC. The primary objective of the analysis was to determine progression-free survival (PFS) of these patients. PATIENTS AND METHODS : Eligible patients from the ZETA trial were divided into 4 disease severity subgroups: progression and symptoms, symptoms only, [...]

Mené sur 61 patientes atteintes d’un carcinome séreux de l’utérus surexprimant Her2/Neu, de stade avancé ou récidivant, cet essai de phase II évalue l’efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité de l’ajout du trastuzumab à un traitement combinant carboplatine et paclitaxel (durée médiane de suivi : 25,9 mois)

Randomized Phase II Trial of Carboplatin–Paclitaxel Compared with Carboplatin–Paclitaxel–Trastuzumab in Advanced (Stage III–IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis

Amanda N. Fader, Dana M. Roque, Eric Siegel, Natalia Buza (et al.)

Purpose: Uterine-serous-carcinoma (USC) is an aggressive variant of endometrial cancer. On the basis of preliminary results of a multicenter, randomized phase II trial, trastuzumab (T), a humanized-mAb targeting Her2/Neu, in combination with carboplatin/paclitaxel (C/P), is recognized as an alternative in treating advanced/recurrent HER2/Neu-positive USC. We report the updated survival analysis of NCT01367002. Patients and Methods: Eligible patients had stage III to IV or recurrent disease. [...]

Menée à partir de données portant sur 30 patientes atteintes d'un cancer métastatique du sein traité entre 2017 et 2019 (durée minimale de suivi : 6 mois), cette étude évalue la toxicité d'un traitement combinant de manière concomitante palbociclib et radiothérapie

Concurrent use of palbociclib and radiation therapy: single-centre experience and review of the literature

Beddok, Arnaud ; Xu, Hao Ping ; Henry, Alexandre Arsène ; Porte, Baptiste ; Fourquet, Alain ; Cottu, Paul ; Kirova, Youlia

Palbociclib in combination with endocrine therapy increases progression-free survival in patients with ER-positive, HER2-negative advanced breast cancer (BC). In this study, we retrospectively evaluated safety in the first patient treated with concurrent use of palbociclib and radiation therapy (RT) in the Curie Institute. Between April 2017 and August 2019, 30 women with metastatic BC received locoregional and/or symptomatic irradiation at a metastatic site concurrently with palbociclib. The [...]

Menée à partir de données portant sur 936 patients atteints d'un carcinome épidermoïde de l'anus et inclus dans un essai de phase III évaluant une chimioradiothérapie concomitante, cette étude évalue l'effet de l'observance thérapeutique sur la survie des patients

Impact of compliance to chemoradiation on long-term outcomes in squamous cell carcinoma of the anus. Results of a post-hoc analysis from the randomized phase III ACT II trial

Glynne-Jones, R. ; Meadows, H. M. ; Lopes, A. ; Muirhead, R. ; Sebag-Montefiore, D. ; Adams, R.

Purpose : Concurrent chemoradiation is standard-of-care for patients with squamous cell carcinoma of the anus (SCCA). Poor compliance to chemotherapy, radiotherapy treatment interruptions and unplanned breaks may impact adversely on long-term outcomes. Methods : The ACT II trial recruited 940 patients with localized SCCA, and assigned patients to mitomycin (week 1) or cisplatin (weeks 1 and 5), with fluorouracil (weeks 1 & 5) and radiotherapy (50·4Gy in 28 fractions over 38 days). This post-hoc [...]

Cet article présente les recommandations de l'"European Society for Medical Oncology" pour l'optimisation et la standardisation du processus d'identification et de sélection des néoantigènes dans le cadre d'immunothérapies

Neoantigen prediction and computational perspectives towards clinical benefit: recommendations from the ESMO Precision Medicine Working Group

De Mattos-Arruda, L. ; Vazquez, M. ; Finotello, F. ; Lepore, R. ; Porta, E. ; Hundal, J. ; Amengual-Rigo, P. ; Ng, C. K. Y. ; Valencia, A. ; Carrillo, J. ; Chan, T. A. ; Guallar, V. ; McGranahan, N. ; Blanco, J. ; Griffith, M.

Background : The use of next-generation sequencing technologies has enabled the rapid identification of non-synonymous somatic mutations in cancer cells. Neoantigens are mutated peptides derived from somatic mutations not present in normal tissues that may result in the presentation of tumour-specific peptides capable of eliciting antitumour T-cell responses. Personalised neoantigen-based cancer vaccines and adoptive T-cell therapies have been shown to prime host immunity against tumour cells [...]

Cet article passe en revue les études concernant les fonctions et la structure du récepteur clever-1 ainsi que son rôle dans la résistance aux immunothérapies, la croissance et la propagation tumorales

New tools to prevent cancer growth and spread: a ‘Clever’ approach

Hollmén, Maija ; Figueiredo, Carlos R. ; Jalkanen, Sirpa

Clever-1 (also known as Stabilin-1 and FEEL-1) is a scavenger receptor expressed on lymphatic endothelial cells, sinusoidal endothelial cells and immunosuppressive monocytes and macrophages. Its role in cancer growth and spread first became evident in Stab1–/– knockout mice, which have smaller primary tumours and metastases. Subsequent studies in mice and humans have shown that immunotherapeutic blockade of Clever-1 can activate T-cell responses, and that this response is mainly mediated by a [...]

Cet article présente une nouvelle approche, consistant à recréer à partir de l'auto-assemblage et de la prolifération de différents types de cellules issues de patients (cellules immunitaires, fibroblastiques et épithéliales) des tumeurs possédant les caractéristiques structurelles et fonctionnelles des tumeurs d'origine, pour évaluer in vitro la réponse tumorale à des anticancéreux

Patient-derived tumor-like cell clusters for drug testing in cancer therapy

Yin, Shenyi ; Xi, Ruibin ; Wu, Aiwen ; Wang, Shu ; Li, Yingjie ; Wang, Chaobin ; Tang, Lei ; Xia, Yuchao ; Yang, Di ; Li, Juan ; Ye, Buqing ; Yu, Ying ; Wang, Junyi ; Zhang, Hanshuo ; Ren, Fei ; Zhang, Yuanyuan ; Shen, Danhua ; Wang, Lin ; Ying, Xiangji ; Li, Zhongwu ; Bu, Zhaode ; Ji, Xin ; Gao, Xiangyu ; Jia, Yongning ; Jia, Ziyu ; Li, Nan ; Li, Ziyu ; Ji, Jia-Fu ; Xi, Jianzhong Jeff

Despite recent advances in medicine, identifying the optimal treatment regimen for each patient with cancer remains difficult and often imprecise. There are now multiple methods for analyzing a tumor’s drug sensitivity, including tumor organoids and patient-derived xenografts, but each has its own drawbacks such as a lack of tumor stroma or the time required to obtain results. The approach designed by Yin et al., patient-derived tumor-like cell clusters, aims to overcome some of these [...]

Cet article présente la mise à jour 2020 des recommandations de l'"European Association of Urology" concernant notamment le diagnostic et le traitement d'un carcinome urothélial des voies urinaires supérieures

European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2020 Update

Rouprêt, Morgan ; Babjuk, Marko ; Burger, Maximilian ; Capoun, Otakar ; Cohen, Daniel ; Compérat, Eva M. ; Cowan, Nigel C. ; Dominguez-Escrig, Jose L. ; Gontero, Paolo ; Hugh Mostafid, A. ; Palou, Joan ; Peyronnet, Benoit ; Seisen, Thomas ; Soukup, Viktor ; Sylvester, Richard J. ; Rhijn, Bas W. G. van ; Zigeuner, Richard ; Shariat, Shahrokh F.

Objective : To provide an overview of the EAU guidelines on UTUC as an aid to clinicians. Evidence acquisition : The recommendations provided in the current guidelines are based on a thorough review of available UTUC guidelines and articles identified following a systematic search of Medline. Data on urothelial malignancies and UTUC were searched using the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract carcinoma, renal pelvis, ureter, bladder cancer, [...]