Immune phenotype-genotype associations in primary clear cell renal cell carcinoma and matched metastatic tissue.

Adjuvant immunotherapy has been recently recommended for patients with metastatic ccRCC, but there are no tissue biomarkers to predict treatment response in ccRCC. Potential predictive biomarkers are mainly assessed in primary tumor tissue, whereas metastases remain understudied. To explore potential differences between genomic alterations and immune phenotypes in primary tumors and their matched metastases, we analyzed primary tumors (PTs) of 47 ccRCC patients and their matched distant metastases (METs) by comprehensive targeted parallel sequencing, whole-genome copy number variation (CNV) analysis, determination of microsatellite instability (MSI) and tumor mutational burden (TMB). We quantified the spatial distribution of tumor-infiltrating CD8+ T cells, and co-expression of the T-cell-exhaustion marker TOX by digital immunoprofiling and quantified tertiary lymphoid structures (TLS). Most METs were pathologically "cold". Inflamed, pathologically "hot" PTs were associated with a decreased disease-free survival (DFS), worst for patients with high levels of CD8+TOX+ T cells. Interestingly, inflamed METs showed a relative increase of exhausted CD8+TOX+ T cells and increased accumulative size of TLS compared to PTs. Integrative analysis of molecular and immune phenotypes revealed BAP1 and CDKN2A/B deficiency to be associated with an inflamed immune phenotype. Our results highlight the distinct spatial distribution and differentiation of CD8+ T cells at metastatic sites, and the association of an inflamed microenvironment with specific genomic alterations.

Spatial Distribution of Recurrence and Long-Term Toxicity Following Dose Escalation to the Dominant Intra-Prostatic Nodule for Intermediate-High-Risk Prostate Cancer: Insights from a Phase I/II Study.

Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intra-prostatic nodule (DIN). Materials and methods: In 33 patients with intermediate-high-risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and 68Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25-74% for partial overlap, were assessed. Long-term toxicity is reported. Results: All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17-76 months), affecting 13 out of 33 patients (39.4%). Intra-prostatic recurrences occurred in 7 patients (21%), with ≥75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patients. Notably, five patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intra-prostatic recurrences. Extended follow-up revealed late grade ≥ 2 GU and GI toxicity in 18% (n = 6) and 6% (n = 2) of the patients. Conclusions: Among patients with intermediate-high-risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: Focal dose-escalated prostate SBRT prevented recurrences in the dominant nodule; however, extra-prostatic recurrence sites were frequent.

[Oncology: what's new in 2023]. / Oncologie: ce qui a changé en 2023.

The oncology field continues its remarkable evolution over the years, with promising advances leading to innovative and individualized treatments. The development of new molecules, the identification of new therapeutic targets and the search for new sequences or combinations promise to revolutionize cancer treatments and contribute to improving survival rates, patients' quality of life and to open new perspective in oncology research. In this article, the newest data released in 2023 are reviewed.

Le domaine de l'oncologie poursuit son évolution remarquable au fil des années, avec des avancées prometteuses ouvrant la voie à des traitements novateurs et individualisés. L'élaboration de nouvelles molécules, l'identification de nouvelles cibles thérapeutiques et la recherche de nouvelles séquences ou combinaisons de traitements promettent de révolutionner la prise en charge du cancer et de contribuer à améliorer les taux de survie, la qualité de vie des patients et à ouvrir de nouvelles perspectives dans la recherche en oncologie. Dans cet article, les nouveautés parues en 2023 sont passées en revue.

Perioperative Chemoimmunotherapy With Durvalumab for Muscle-Invasive Urothelial Carcinoma: Primary Analysis of the Single-Arm Phase II Trial SAKK 06/17.

PURPOSE: The integration of immunotherapy in the perioperative setting of muscle-invasive urothelial carcinoma (MIUC) appears promising. SAKK 06/17 investigated the addition of neoadjuvant durvalumab to gemcitabine/cisplatin (GC) chemotherapy followed by radical surgery and adjuvant checkpoint inhibition with durvalumab. PATIENTS AND METHODS: SAKK 06/17 was an investigator-initiated, open-label, single-arm phase II study including cisplatin-fit patients with stage cT2-T4a cN0-1 operable MIUC. Four cycles of neoadjuvant GC in combination with four cycles of durvalumab (start with GC cycle 2) were administered, followed by radical surgery. Adjuvant durvalumab was given for 10 cycles. The primary end point was event-free survival (EFS) at 2 years. RESULTS: Sixty one patients were accrued at 12 sites. The full analysis set consisted of 57 patients, 54 (95%) had bladder cancer. Median follow-up was 40 months. The primary end point was met, with EFS at 2 years of 76% (one-sided 90% CI [lower bound], 67%; two-sided 95% CI, 62 to 85). EFS at 3 years was 73% (95% CI, 59 to 83). Complete pathologic response in resected patients (N = 52) was achieved in 17 patients (33%), and 31 (60%) had pathologic response

Interdisciplinary Swiss consensus recommendations on staging and treatment of advanced prostate cancer.

The management of prostate cancer is undergoing rapid changes in all disease settings. Novel imaging tools for diagnosis have been introduced, and the treatment of high-risk localized, locally advanced and metastatic disease has changed considerably in recent years. From clinical and health-economic perspectives, a rational and optimal use of the available options is of the utmost importance. While international guidelines list relevant pivotal trials and give recommendations for a variety of clinical scenarios, there is much room for interpretation, and several important questions remain highly debated. The goal of developing a national consensus on the use of these novel diagnostic and therapeutic strategies in order to improve disease management and eventually patient outcomes has prompted a Swiss consensus meeting. Experts from several specialties, including urology, medical oncology, radiation oncology, pathology and nuclear medicine, discussed and voted on questions of the current most important areas of uncertainty, including the staging and treatment of high-risk localized disease, treatment of metastatic hormone-sensitive prostate cancer (mHSPC) and use of new options to treat metastatic castration-resistant prostate cancer (mCRPC).

[Prostate cancer in the era of precision medicine: a new horizon]. / Cancer de la prostate à l'ère de la médecine de précision : un nouvel horizon.

Precision medicine is playing an increasingly crucial role in the treatment of prostate cancer. By tailoring treatments to the unique characteristics of patients and their tumors, this approach enables more targeted and personalized care, ultimately improving patient survival. In this article, we discuss the targeted therapies that have recently changed the management of this cancer.

La médecine de précision joue un rôle de plus en plus crucial dans le traitement du cancer de la prostate. En adaptant les traitements aux caractéristiques individuelles des patients et de leurs tumeurs, cette approche permet une prise en charge plus ciblée et personnalisée, contribuant ainsi à améliorer la survie des patients. Dans cet article, nous abordons les traitements ciblés qui ont récemment transformé la prise en charge de ce cancer.

Toxicity, quality of life, and PSA control after 50 Gy stereotactic body radiation therapy to the dominant intraprostatic nodule with the use of a rectal spacer: results of a phase I/II study.

OBJECTIVES: We conducted a phase I/II prospective trial to determine whether stereotactic dose escalation to the dominant intra-prostatic nodule (DIN) up to 50 Gy incorporating a rectal balloon spacer is safe, does not affect patient quality of life, and preserves local control in patients with intermediate-high risk PCa. METHODS: Eligible patients included males with stage ≤T3b localized disease, a prostate-specific antigen (PSA) level ≤50 , International Prostate Symptom Score (IPSS) ≤14, and a gland volume ≤70 cm3. Patients underwent perirectal spacer placement, followed by a planning MRI and were subsequently treated with SBRT doses of 36.25 Gy in five fractions to the whole prostate while simultaneously escalating doses to the magnetic resonance image visible DIN up to 50 Gy. Primary endpoint: safety. Secondary endpoints: biochemical control, quality of life (QofL), and dosimetry outcome. RESULTS: Nine patients were treated in the Phase I part of the study. Dose limiting toxicities (DLTs) were not observed. Further characterization of tolerability and efficacy was conducted in the subsequent 24 patients irradiated at the recommended Phase II dose (50 Gy, RP2D). At a median follow-up of 61 months, biochemical control is 69%. Grade 1 and 2 acute GU and GI toxicity was 57.5 and 15%, and 24.2 and 6.1%, respectively. Grade 1 and 2 late GU and GI toxicity was 66.6 and 12.1%, and 15.1 and 3%, respectively. No Grade 3 or higher toxicity was reported. QofL data confirmed physician's reported side effects. Dosimetry analysis showed adherence to the doses prescribed in the protocol. CONCLUSIONS: SBRT of the whole prostate with 36.25 Gy in 5 fractions and dose escalation to 50 Gy to the DIN, when combined with a peri-rectal balloon spacer, was tolerable and established the RP2D. QofL analysis showed minimal negative impact in GU, GI, and sexual domains. ADVANCES IN KNOWLEDGE: Extreme hypofractionated prostate radiation therapy with focal dose escalation to the DIN is well tolerated with efficacy comparable to normal fractionated radiation therapy.

[Oncology: what's new in 2022]. / Oncologie : ce qui a changé en 2022.

The past year has brought several innovations in medical oncology, opening up promising new options for many solid tumors, both localized and metastatic. Immunotherapy, a real spearhead of emerging therapies in metastatic diseases, is seeing its use extend to adjuvant and neoadjuvant modalities, particularly in colon and lung cancers. 2022 also sees a great deal of focus on targeted therapies, as well as on antibody-drug conjugates, which creates new standards in both breast and lung cancers. Here we present the major advances in solid tumors.

L'année écoulée a apporté son lot d'innovations en oncologie médicale, ouvrant de nouvelles options prometteuses pour bon nombre de tumeurs solides, qu'elles soient localisées ou métastatiques. L'immunothérapie, véritable fer de lance des thérapies émergentes dans les maladies métastatiques, voit son usage s'étendre à des modalités adjuvantes et néoadjuvantes, notamment dans les cancers du côlon et du poumon. 2022 donne également la part belle aux thérapies ciblées mais aussi aux conjuguées anticorps-médicaments qui apportent de nouveaux standards tant pour les cancers du sein que du poumon. Nous vous présentons ici les avancées majeures concernant les tumeurs solides.

Single-dose carboplatin followed by involved-node radiotherapy for stage IIA and stage IIB seminoma (SAKK 01/10): a single-arm, multicentre, phase 2 trial.

BACKGROUND: Standard treatment options for patients with stage IIA or stage IIB seminoma include either para-aortic and pelvic radiotherapy or three to four cycles of cisplatin-based combination chemotherapy. These options result in 3-year progression free survival rates of at least 90%, but bear risks for acute and late toxic effects, including secondary malignancies. We tested a novel approach combining de-escalated chemotherapy with de-escalated involved node radiotherapy, with the aim of reducing toxicity while preserving efficacy. METHODS: In the single-arm, multicentre, phase 2 SAKK 01/10 trial, patients with stage IIA or IIB classic seminoma (either at primary diagnosis or at relapse during active surveillance for stage I) were enrolled at ten centres of the Swiss Group for Clinical Cancer Research and ten centres of the German Testicular Cancer Study Group. WHO performance status 0-2, age 18 years or older, and adequate bone marrow and kidney function were required for eligibility. Treatment comprised one cycle of carboplatin (area under the curve 7) followed by involved-node radiotherapy (30 Gy in 15 fractions for stage IIA disease and 36 Gy in 18 fractions for stage IIB disease). The primary endpoint was 3-year progression-free survival. Efficacy analyses were done on the full analysis set, which comprised all patients who signed the informed consent, were registered in the trial, initiated trial treatment, and met all medically relevant inclusion or exclusion criteria. Safety was assessed in all patients who were treated at least once with one of the trial treatments. The study is ongoing but no longer recruiting, and is registered with Clinicaltrials.gov, NCT01593241. FINDINGS: Between Oct 18, 2012, and June 22, 2018, 120 patients were registered in the study. 116 patients were eligible and started treatment according to the study protocol (46 patients with stage IIA disease and 70 with stage IIB disease). After a median follow-up of 4·5 years (IQR 3·9-6·0), 3-year progression-free survival was 93·7% (90% CI 88·5-96·6). With a target progression-free survival of 95% at 3 years, the primary endpoint was not met. Acute treatment-related adverse events of any grade were noted in 58 (48%) of 116 patients, and grade 3 or 4 treatment-related adverse events occurred in the form of neutropenia in five (4%) patients, thrombocytopenia in three (3%) patients, and vomiting in one (1%) patient. No treatment-related deaths and no late treatment-related adverse events were reported. Serious adverse events were reported in five (4%) of 116 patients (one transient creatinine increase and four second primary tumours). INTERPRETATION: Despite the fact that the primary endpoint was not met, we observed favourable 3-year progression-free survival with single-dose carboplatin area under the curve 7 and involved-node radiotherapy, with minimal toxic effects. Our findings might warrant discussion with patients about the SAKK 01/10 regimen as an alternative to standard-of-care treatment, but more research on this strategy is needed. FUNDING: Swiss State Secretariat for Education, Research and Innovation and Rising Tide Foundation for Clinical Cancer Research.

First-in-human phase I/II, open-label study of the anti-OX40 agonist INCAGN01949 in patients with advanced solid tumors.

BACKGROUND: OX40 is a costimulatory receptor upregulated on antigen-activated T cells and constitutively expressed on regulatory T cells (Tregs). INCAGN01949, a fully human immunoglobulin G1κ anti-OX40 agonist monoclonal antibody, was designed to promote tumor-specific immunity by effector T-cell activation and Fcγ receptor-mediated Treg depletion. This first-in-human study was conducted to determine the safety, tolerability, and preliminary efficacy of INCAGN01949. METHODS: Phase I/II, open-label, non-randomized, dose-escalation and dose-expansion study conducted in patients with advanced or metastatic solid tumors. Patients received INCAGN01949 monotherapy (7-1400 mg) in 14-day cycles while deriving benefit. Safety measures, clinical activity, pharmacokinetics, and pharmacodynamic effects were assessed and summarized with descriptive statistics. RESULTS: Eighty-seven patients were enrolled; most common tumor types were colorectal (17.2%), ovarian (8.0%), and non-small cell lung (6.9%) cancers. Patients received a median three (range 1-9) prior therapies, including immunotherapy in 24 patients (27.6%). Maximum tolerated dose was not reached; one patient (1.1%) receiving 350 mg dose reported dose-limiting toxicity of grade 3 colitis. Treatment-related adverse events were reported in 45 patients (51.7%), with fatigue (16 (18.4%)), rash (6 (6.9%)), and diarrhea (6 (6.9%)) being most frequent. One patient (1.1%) with metastatic gallbladder cancer achieved a partial response (duration of 6.3 months), and 23 patients (26.4%) achieved stable disease (lasting >6 months in one patient). OX40 receptor occupancy was maintained over 90% among all patients receiving doses of ≥200 mg, while no treatment-emergent antidrug antibodies were detected across all dose levels. Pharmacodynamic results demonstrated that treatment with INCAGN01949 did not enhance proliferation or activation of T cells in peripheral blood or reduce circulating Tregs, and analyses of tumor biopsies did not demonstrate any consistent increase in effector T-cell infiltration or function, or decrease in infiltrating Tregs. CONCLUSION: No safety concerns were observed with INCAGN01949 monotherapy in patients with metastatic or advanced solid tumors. However, tumor responses and pharmacodynamic effects on T cells in peripheral blood and post-therapy tumor biopsies were limited. Studies evaluating INCAGN01949 in combination with other therapies are needed to further evaluate the potential of OX40 agonism as a therapeutic approach in patients with advanced solid tumors. TRIAL REGISTRATION NUMBER: NCT02923349.

Overcoming Immune Resistance With Radiation Therapy in Prostate Cancer.

Prostate cancer is the second most common cancer in men and represents a significant healthcare burden worldwide. Therapeutic options in the metastatic castration-resistant setting remain limited, despite advances in androgen deprivation therapy, precision medicine and targeted therapies. In this review, we summarize the role of immunotherapy in prostate cancer and offer perspectives on opportunities for future development, based on current knowledge of the immunosuppressive tumor microenvironment. Furthermore, we discuss the potential for synergistic therapeutic strategies with modern radiotherapy, through modulation of the tumor microenvironment. Emerging clinical and pre-clinical data suggest that radiation can convert immune desert tumors into an inflamed immunological hub, potentially sensitive to immunotherapy.

Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476).

Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multiarm, multistage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3 years after the first results. Standard-of-care (SOC) was androgen deprivation therapy. The comparison randomised patients 1:1 to SOC-alone with or without daily abiraterone acetate 1000 mg + prednisolone 5 mg (SOC + AAP), continued until disease progression. The primary outcome measure was overall survival. Metastatic disease risk group was classified retrospectively using baseline CT and bone scans by central radiological review and pathology reports. Analyses used Cox proportional hazards and flexible parametric models, accounting for baseline stratification factors. One thousand and three patients were contemporaneously randomised (November 2011 to January 2014): median age 67 years; 94% newly-diagnosed; metastatic disease risk group: 48% high, 44% low, 8% unassessable; median PSA 97 ng/mL. At 6.1 years median follow-up, 329 SOC-alone deaths (118 low-risk, 178 high-risk) and 244 SOC + AAP deaths (75 low-risk, 145 high-risk) were reported. Adjusted HR = 0.60 (95% CI: 0.50-0.71; P = 0.31 × 10-9 ) favoured SOC + AAP, with 5-years survival improved from 41% SOC-alone to 60% SOC + AAP. This was similar in low-risk (HR = 0.55; 95% CI: 0.41-0.76) and high-risk (HR = 0.54; 95% CI: 0.43-0.69) patients. Median and current maximum time on SOC + AAP was 2.4 and 8.1 years. Toxicity at 4 years postrandomisation was similar, with 16% patients in each group reporting grade 3 or higher toxicity. A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC + abiraterone acetate + prednisolone, irrespective of metastatic disease risk group.

Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design.

BACKGROUND: Current standard of care for metastatic castration-sensitive prostate cancer supplements androgen deprivation therapy with either docetaxel, second-generation hormonal therapy, or radiotherapy. We aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to standard of care. METHODS: We conducted an open-label, randomised, phase 3 study with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland. Eligible patients were male, aged 18 years or older, with histologically confirmed or cytologically confirmed de novo metastatic prostate adenocarcinoma, and an Eastern Cooperative Oncology Group performance status of 0-1 (or 2 due to bone pain). Participants were randomly assigned (1:1:1:1) to standard of care (androgen deprivation therapy alone or with intravenous docetaxel 75 mg/m2 once every 3 weeks), standard of care plus radiotherapy, standard of care plus abiraterone (oral 1000 mg abiraterone once daily plus oral 5 mg prednisone twice daily), or standard of care plus radiotherapy plus abiraterone. Neither the investigators nor the patients were masked to treatment allocation. The coprimary endpoints were radiographic progression-free survival and overall survival. Abiraterone efficacy was first assessed in the overall population and then in the population who received androgen deprivation therapy with docetaxel as standard of care (population of interest). This study is ongoing and is registered with ClinicalTrials.gov, NCT01957436. FINDINGS: Between Nov 27, 2013, and Dec 20, 2018, 1173 patients were enrolled (one patient subsequently withdrew consent for analysis of his data) and assigned to receive standard of care (n=296), standard of care plus radiotherapy (n=293), standard of care plus abiraterone (n=292), or standard of care plus radiotherapy plus abiraterone (n=291). Median follow-up was 3·5 years (IQR 2·8-4·6) for radiographic progression-free survival and 4·4 years (3·5-5·4) for overall survival. Adjusted Cox regression modelling revealed no interaction between abiraterone and radiotherapy, enabling the pooled analysis of abiraterone efficacy. In the overall population, patients assigned to receive abiraterone (n=583) had longer radiographic progression-free survival (hazard ratio [HR] 0·54, 99·9% CI 0·41-0·71; p<0·0001) and overall survival (0·82, 95·1% CI 0·69-0·98; p=0·030) than patients who did not receive abiraterone (n=589). In the androgen deprivation therapy with docetaxel population (n=355 in both with abiraterone and without abiraterone groups), the HRs were consistent (radiographic progression-free survival 0·50, 99·9% CI 0·34-0·71; p<0·0001; overall survival 0·75, 95·1% CI 0·59-0·95; p=0·017). In the androgen deprivation therapy with docetaxel population, grade 3 or worse adverse events occurred in 217 (63%) of 347 patients who received abiraterone and 181 (52%) of 350 who did not; hypertension had the largest difference in occurrence (76 [22%] patients and 45 [13%], respectively). Addition of abiraterone to androgen deprivation therapy plus docetaxel did not increase the rates of neutropenia, febrile neutropenia, fatigue, or neuropathy compared with androgen deprivation therapy plus docetaxel alone. INTERPRETATION: Combining androgen deprivation therapy, docetaxel, and abiraterone in de novo metastatic castration-sensitive prostate cancer improved overall survival and radiographic progression-free survival with a modest increase in toxicity, mostly hypertension. This triplet therapy could become a standard of care for these patients. FUNDING: Janssen-Cilag, Ipsen, Sanofi, and the French Government.

[2021 Oncology update]. / Oncologie.

Despite COVID-19 pandemic, which is still deeply affecting world economy and global health, medical oncology specialists keep pursuing their effort for the identification of new therapeutic options to improve patients' life expectancy and quality of life. 2021 confirms the immunotherapy efficacy, alone or in combination with other modalities, across several indications. This year, we are summarizing the new approaches in the following sectors: lung, breast, melanoma, gynecological, digestive, urological and ENT areas.

En dépit de la pandémie de Covid-19 qui continue à grandement impacter l'économie mondiale et la santé, l'oncologie médicale poursuit sa quête d'identification de nouvelles options thérapeutiques ayant pour buts la prolongation de l'espérance de vie et l'amélioration de la qualité de vie de ses patients, en nombre croissant. L'année 2021 confirme également l'efficacité de l'immunothérapie, seule ou en combinaison à d'autres modalités, dans de nombreuses indications. Cette année, nous vous résumons les nouvelles approches dans les domaines suivants: poumon, sein, mélanome, sphères gynécologique, digestive, urologique et ORL.

Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy.

Developing strategies to inflame tumors is critical for increasing response to immunotherapy. Here, we report that low-dose radiotherapy (LDRT) of murine tumors promotes T-cell infiltration and enables responsiveness to combinatorial immunotherapy in an IFN-dependent manner. Treatment efficacy relied upon mobilizing both adaptive and innate immunity and depended on both cytotoxic CD4+ and CD8+ T cells. LDRT elicited predominantly CD4+ cells with features of exhausted effector cytotoxic cells, with a subset expressing NKG2D and exhibiting proliferative capacity, as well as a unique subset of activated dendritic cells expressing the NKG2D ligand RAE1. We translated these findings to a phase I clinical trial administering LDRT, low-dose cyclophosphamide, and immune checkpoint blockade to patients with immune-desert tumors. In responsive patients, the combinatorial treatment triggered T-cell infiltration, predominantly of CD4+ cells with Th1 signatures. Our data support the rational combination of LDRT with immunotherapy for effectively treating low T cell-infiltrated tumors. SIGNIFICANCE: Low-dose radiation reprogrammed the tumor microenvironment of tumors with scarce immune infiltration and together with immunotherapy induced simultaneous mobilization of innate and adaptive immunity, predominantly CD4+ effector T cells, to achieve tumor control dependent on NKG2D. The combination induced important responses in patients with metastatic immune-cold tumors.This article is highlighted in the In This Issue feature, p. 1.

[Cancer center clinical nurse: The experience of the CHUV Prostate Cancer Center]. / Infirmière clinicienne de centre du cancer : l'expérience du Centre de la prostate du CHUV.

The University Hospital of Lausanne has heavily invested in the development of interdisciplinary oncology centers to improve the quality of care, and structure research and training. By integrating specialist nurses, it follows international recommendations. These specialists' nurses rephrase the information given by the doctor and ensure patients' understanding. They assess the patient's psychosocial situation and provides guidance if necessary. They support the patient in making informed choices about treatment and coping strategies. In addition to the outpatient clinics planned in accordance with the care pathway, she can be contacted between appointments to answer questions or concerns of any kind. This article shows the added value of these nurses in the care of oncology patients.

Le CHUV s'est fortement investi dans le développement de centres interdisciplinaires en oncologie afin d'améliorer la qualité de la prise en charge, de structurer la recherche et la formation. En y intégrant des infirmières cliniciennes, il suit les recommandations internationales. Ces infirmières reprennent les informations données par le médecin et s'assurent de la compréhension du patient. Elles évaluent sa situation psychosociale et l'orientent au besoin. Elles soutiennent le patient dans ses choix de traitement ainsi que dans ses stratégies d'adaptation. Outre les entretiens planifiés en fonction du parcours de soins, elles sont joignables entre les rendez-vous pour répondre à des questions ou préoccupations de tout ordre. Cet article montre la plus-value que la présence de ces infirmières offre à la prise en charge des patients oncologiques.

Swiss germ-cell cancer consensus recommendations.

Approximately 420 men are diagnosed with germ-cell cancer (GCC) in Switzerland each year. Recent international guidelines outline management issues, but many aspects remain controversial in an area of highly individualised treatments. Even more than in other tumour types, in GCC the challenge is to choose exactly the correct treatment for an individual patient. Overtreatment in patients likely to be cured must be avoided to reduce long-term toxicities. On the other hand, treatment intensification is required in patients presenting with adverse prognostic factors. Therefore, referral to expert centres or consultations with an expert for a second opinion is strongly recommended. In 2020, Swiss experts discussed their strategies in a consensus meeting during the virtual Swiss Oncology and Haematology Congress (SOHC) in order to harmonise their concepts and to suggest optimal strategies for the management of GCC patients in Switzerland. Votes on controversial issues were obtained and are presented in this review wherever applicable.

A new method to visualize and to spare the ureters during SBRT for oligo metastatic patients.

This article describes a ureter-sparing procedure used to treat lymph node metastases with SBRT. We delivered 35 Gy in 5 fractions of 7 Gy to patients with lesions located less than 7 mm from the ureters using a urography CT scan for planification. Two dosimetry plans were created, one using a CT scan urography-based contour and the other using the native phase. PTV coverage were not statistically different but this technique was able to significantly reduce median delivered Dmax to the ureters. These preliminary results demonstrate the feasibility of locating the ureters in a planning CT scan to protect them.

Active surveillance in males with low- to intermediate-risk localized prostate cancer: A modern prospective cohort study.

PURPOSE: To compare the clinical outcome of males with low-risk and favorable intermediate-risk prostate cancer managed within a standardized modern protocol of active surveillance. MATERIALS AND METHODS: This was a prospective cohort study with strict and expanded active surveillance criteria in males with prostate cancer. Baseline assessment included multiparametric magnetic resonance imaging (mpMRI), extended systematic biopsy, and software-based MR-targeted biopsy. Follow-up included biannual prostate-specific antigen (PSA) check, mpMRI, and control biopsy once a year for the first 2 years, and afterward mpMRI every 2 years with additional tests as clinically indicated. The primary outcome was the transition rate to active treatment. RESULTS: A total of 51 patients were included: 17 (33%) and 34 (67%) followed protocols of strict (study arm 1) and expanded (study arm 2) active surveillance criteria, respectively. Median age and PSA were 65 years (IQR, 60-69 years) and 5.3 ng/mL (IQR, 4.5-7.7 ng/mL), respectively. At baseline, a median of 2 (IQR, 1-3) cores were positive out of 13 (IQR, 12-14) cores; 22 males (43%) had visible mpMRI lesions. Eight males (24%) in study arm 2 had Gleason score 3+4. After a median follow-up of 36 months (IQR, 24-48 mo), no patient in study arm 1 compared with 17 patients (33%) in arm 2 underwent active treatment (p<0.0005). CONCLUSIONS: Although expanding eligibility criteria leads to a greater transition rate to active treatment, active surveillance should be contemplated in well-selected males with favorable intermediate-risk prostate cancer as the curability window seems to be maintained.

[Immunotherapy for bladder cancer in 2021]. / Immunothérapie dans le cancer de la vessie : mise à jour 2021.

Intravesical immunotherapy with Calmette-Guerin bacillus (BCG) have been used since decades for the treatment of non-muscle invasive bladder cancer and is a proof of principle that immunotherapy works for this malignancy. Since 2016, immune checkpoint inhibitors (ICI) demonstrated clinical benefits in locally advanced or metastatic bladder cancer, providing potentially durable tumor control in first line therapy or upon relapse after standard treatments. Ongoing clinical trials aim to demonstrate the efficiency of ICI for the treatment of localized disease.

L'immunothérapie par instillation de bacille de Calmette-Guérin est utilisée depuis plusieurs décennies dans le cancer de la vessie non musculo-invasif. Cette forme d'immunothérapie locale est témoin de l'efficacité de cette approche thérapeutique. Depuis 2016, les inhibiteurs de points de contrôle immunitaire (IPCI) complètent l'arsenal thérapeutique notamment lors d'une maladie localement avancée ou métastatique. Ils permettent d'obtenir des résultats bénéfiques potentiellement durables en première ligne de traitement et après échec des traitements standards. Des efforts sont en cours afin de démontrer le bénéfice des IPCI dans la prise en charge de la maladie localisée.