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BackgroundImmune checkpoint inhibitors (ICIs) have become a mainstay of cancer treatment. Their immune-boosting quality has one major drawback, their proclivity to induce a broad array of immune-related adverse events (irAEs) affecting, among others, the liver and sharing some similarities with classic autoimmune liver diseases (AILD).We aimed to compare clinical, laboratory and histological features of patients with liver-related irAEs and AILD.MethodsWe systematically compared liver irAEs with AILD, namely autoimmune hepatitis (AIH) and primary biliary cholangitis, regarding their clinical, laboratory, and histological features.ResultsTwenty-seven patients with liver irAEs (ICI group) and 14 patients with AILD were identified. We observed three distinct ICI-induced histological liver injury patterns: hepatitic (52%), cholangitic (19%), and mixed (29%). When comparing the ICI and AILD groups, centrilobular injury as well as granuloma formation were more prevalent in the former (p=0.067 and 0.002, respectively). CD4+/CD8+ T cell ratios were heterogeneous between the two groups, without statistically significant difference but with a trend toward increased CD8+ T cells among hepatitic irAEs as compared with AIH. Pattern of liver function test alteration was predictive for the type of irAEs but did not correlate with histological severity.ConclusionsLiver irAEs have broad clinical, laboratory and histological presentations. Histological features of irAEs and AILD are distinct, likely underpinning their different immunological mechanisms.

OBJECTIVES Although video-assisted thoracic surgery (VATS) has shortened hospitalization duration for non-small-cell lung cancer (NSCLC) patients, the factors associated with early discharge remain unclear. This study aimed to identify patients eligible for a 72-h stay after VATS anatomical resection. METHODS Monocentric retrospective study including all consecutive patients undergoing VATS anatomical resection for NSCLC between February 2010 and December 2019. Two groups were defined according to the discharge: ‘early discharge’ (within 72 postoperative hours) and ‘routine discharge’ (at >72 postoperative hours). RESULTS A total of 660 patients with a median age of 66.5 years (interquartile range 60–73 years) (female/male: 321/339) underwent VATS anatomical pulmonary resection for NSCLC [segmentectomy in 169 (25.6%), lobectomy in 481 (72.9%), bilobectomy in 8 (1.2%) and pneumonectomy in 2 (0.3%) patients]. The cardiopulmonary and Clavien–Dindo III–IV postoperative complication rates were 32.6% and 7.7%, respectively. The median postoperative length of stay was 6 days (interquartile range 4–10 days). In total, 119 patients (18%) could be discharged within 72 h of surgery. On multivariable analysis, the factors significantly associated with an increased likelihood of early discharge were: body mass index >20 kg/m2 [odds ratio (OR) 2.37], absence of prior cardiopathy (OR 2), diffusing capacity of the lung for carbon monoxide >60% (OR 1.82), inclusion in an enhanced recovery after surgery protocol (OR 2.23), use of a single chest tube (OR 5.73) and postoperative transfer to the ward (OR 4.84). Factors significantly associated with a decreased likelihood of early discharge were: age >60 years (OR 0.53), American Society of Anaesthesiologists score >2 (OR 0.46) and use of an epidural catheter (OR 0.41). Readmission rates were not statistically different between both groups (5.9% vs 3.1%; P = 0.17). CONCLUSIONS Age, pulmonary functions and comorbidities may influence discharge after VATS anatomical resection. The early discharge does not increase readmission rates.

In recent years, new therapeutic strategies for non-small cell lung cancer (NSCLC) have been developed, stemming from a better understanding of oncogenic signaling pathways. The analysis of the alterations of genes involved in NSCLC oncogenesis is now an integral part of the diagnostic approach and opens the way to so-called "targeted" therapies. In this article, we will share the latest therapeutic advances by focusing on alterations of HER2, MET, EGFR and KRAS genes, for which new dedicated treatments have become available.Au cours de ces dernières années, de nouvelles stratégies thérapeutiques pour le cancer du poumon non à petites cellules (CPNPC) se sont développées, découlant d’une meilleure compréhension des voies de signalisation oncogéniques. L’analyse des altérations de gènes impliqués dans le développement de ce sous-type de maladie oncologique fait désormais partie intégrante de la démarche diagnostique et ouvre la voie à des thérapies dites « ciblées ». Nous partagerons dans cet article les dernières avancées thérapeutiques en nous intéressant aux altérations des gènes

Highlights • Abscopal effect is the ability of local RT to induce systemic antitumor effect. • Abscopal effect is increasingly frequent with concomitant immunotherapy and RT. • Abscopal effect remains a rare observation. • We report an abscopal effect in MPM treated with concomitant anti-PD-L1 and RT., The abscopal effect describes the ability of locally administered radiotherapy to induce systemic antitumor effects. Although mentioned for the first time in the 1950s, records of abscopal effects, considered to be immune-mediated, are scarce with radiotherapy alone. However, with the continued development and use of immunotherapy, reports on the abscopal effect have become increasingly frequent during the last decade. Here, we report a patient with advanced malignant pleural mesothelioma who had progressive disease while on the anti-PDL1 inhibitor pembrolizumab and showed an abscopal response after palliative radiotherapy.

Highlights • The first curative management of symptomatic cardiac metastasis of a lung cancer using SBRT. • A CR was obtained and no further specific treatment was needed., Although cardiac metastases (CM) are more common than primary cardiac malignant tumors, they remain a rare localization of metastatic cancer. Until recently, CM were surgically treated as a palliative approach because of a lack of ablative solutions even for oligometastatic patients. Technological advances in radiation therapy (RT) in thoracic oncology have led to high precision delivery that enlarged the indications for stereotactic body radiotherapy (SBRT). To date, there are limited reports of cardiac SBRT for CM. Herein, we report a cardiac SBRT performed in curative intent for a lung cancer patient metastatic to the heart.

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.

Highlights • Stereotactic body radiotherapy is a well-recognized option for treatment of early stage non-small cell lung cancer. • Locale relapse is rare but still remains a challenge to manage. • SBRT lung reirradiation is uncommon and few studies report its technique and the outcome. • SBRT lung reirradiation may be considered in an appropriate setting and in a well selected population., Introduction Local recurrence after lung SBRT for early stage NSCLC is rare but its treatment remains a challenge due to limited surgical options. We report a case series of 5 patients treated by stereotactic lung salvage reirradiation for local relapse after a previous lung SBRT. Material and methods Included patients presented an isolated primary lung relapse within at least the 50% isodose of the previous SBRT treatment. Typical reirradiation schedule was 60 Gy in 8 fractions at isodose 80% and was delivered by Cyberknife® using Synchrony® fiducial tracking system. Dose summations were performed to evaluate the safety of the reirradiation. Results We identified 5 patients presenting peripheral lesions. All reirradiated lesions were locally controlled after a median follow-up of 11.1 months (6,7–12,2), while PFS at 6 months was 60% (n = 3). We did not notice any Grade 3 or more acute or late adverse event. Conclusion We observed encouraging short-term outcome of lung SBRT reirradiation in patients presenting isolated local relapse of an early-stage NSCLC. Further studies are necessary to confirm the safety and efficiency of this salvage treatment approach.

Background: Stereotactic body radiotherapy (SBRT) is recommended for the treatment of inoperable early stage non-small-cell lung cancer and lung oligometastases. The radiation oncology department of the Lausanne University Hospital (CHUV) gathers three different radiotherapy devices able to treat pulmonary lesions in SBRT conditions: CyberKnife® (CK), Helical Tomotherapy® (HT), and volumetric modulated arc therapy (VMAT). The aim of this study is to define the patients’ outcome in terms of irradiation efficacy and toxicities after lung SBRT depending of the choice of the SBRT technique.Methods: We retrospectively analyzed the clinical, radiological, and dosimetric data of patients with primary lung tumor or pulmonary oligometastases treated with SBRT between January 2016 and February 2020. We analyzed descriptive data using the Chi-2 test for proportions and the T-test for means comparisons, survival data by the Kaplan-Meier method and comparisons between groups by the Log-rank test and Cox-regression.Results: We identified 111 patients mostly in good condition (82.9% PS 0-1) with a median age of 71.4 years. One hundred forty-two lesions were treated with a typical fractionation of 55 Gy in 5 fractions, delivered by CK (59.9%), VMAT (38.0%), or HT (2.1%). Compared to other techniques, CK technique allowed to treat comparable gross tumor volume (GTV; 2.1 vs 1.4cc, p = 0.84) with smaller planning treatment volume (PTV; 12.3 vs 21.9 cc, p = 0.013), and was associated with a lower mean lung dose (MLD; 2.6 vs 4.1 Gy, p < 0.001), a lower V5 (13.5 vs 19.9 cc, p = 0.002) and a lower V20 (2.3 vs 5.4 cc, p < 0.001). Local control rates at 2 years were not different depending on the irradiation device, respectively of 96.2% (range, 90.8-100) and 98.1% (range, 94.4-100), p = 0.68. Toxicity incidence was significantly increased with V5 value > 17.2% (56.0 vs 77.4%, p = 0.021). Conclusions: Compared to other SBRT techniques, CK treatments permitted to treat comparable GTV with reduced PTV, MLD, V20, and V5. The dosimetric benefit of CK SBRT was not associated with a clear clinical benefit, with comparable outcome in terms of control rates and toxicity. Toxicity incidence was less frequent when reducing the V5. The use of CK is particularly attractive in case of multiple courses of lung SBRT or in case of local relapse requiring lung re-irradiation.Trial registration: Registered on February 24th 2021, ID 2021-00267, with the authorization of the CER-VD ethics committee (Switzerland).

During the acute phase of the COVID-19 pandemic, hospitals faced a challenge to manage patients, especially those with other comorbidities and medical needs, such as cancer patients. Here, we use Process Mining to analyze real-world therapeutic pathways in a cohort of 1182 cancer patients of the Lausanne University Hospital following COVID-19 infection. The algorithm builds trees representing sequences of coarse-grained events such as Home, Hospitalization, Intensive Care and Death. The same trees can also show probability of death or time-to-event statistics in each node. We introduce a new tool, called Differential Process Mining, which enables comparison of two patient strata in each node of the tree, in terms of hits and death rate, together with a statistical significance test. We thus compare management of COVID-19 patients with an active cancer in the first vs. second COVID-19 waves to quantify hospital adaptation to the pandemic. We also compare patients having undergone systemic therapy within 1 year to the rest of the cohort to understand the impact of an active cancer and/or its treatment on COVID-19 outcome. This study demonstrates the value of Process Mining to analyze complex event-based real-world data and generate hypotheses on hospital resource management or on clinical patient care.

BACKGROUND The strengthening or substitution of intravenous cytotoxic chemotherapy cycles by oral targeted anticancer therapies, such as protein kinase inhibitors (PKIs), has provided impressive clinical benefits and autonomy as well as a better quality of life for patients with cancer. Despite these advances, adverse event management at home and medication adherence remain challenging. In addition, PKI plasma concentrations vary significantly among patients with cancer receiving the same dosage, which could explain part of the observed variability in the therapeutic response. OBJECTIVE The aim of this optimizing oral targeted anticancer therapies (OpTAT) study is to optimize and individualize targeted anticancer treatments to improve patient care and self-monitoring through an interprofessional medication adherence program (IMAP) combined with measurement PKI plasma concentrations. METHODS The OpTAT study has two parts: (1) a 1:1 randomized medication adherence program, in which the intervention consists of regular motivational interviewing sessions between the patient and the pharmacist, along with the delivery of PKIs in electronic monitors, and (2) a systematic collection of blood samples and clinical and biological data for combined pharmacokinetic and pharmacodynamic analysis. On the basis of the electronic monitor data, medication adherence will be compared between groups following the three operational definitions: implementation of treatment during the persistent period, persistence with treatment and longitudinal adherence. The implementation will be described using generalized estimating equation models. The persistence of PKI use will be represented using a Kaplan-Meier survival curve. Longitudinal adherence is defined as the product of persistence and implementation. PKI pharmacokinetics will be studied using a population approach. The relationship between drug exposure and efficacy outcomes will be explored using Cox regression analysis of progression-free survival. The relationship between drug exposure and toxicity will be analyzed using a pharmacokinetic-pharmacodynamic model and by logistic regression analysis. Receiver operating characteristic analyses will be applied to evaluate the best exposure threshold associated with clinical benefits. RESULTS The first patient was included in May 2015. As of June 2021, 262 patients had participated in at least one part of the study: 250 patients gave at least one blood sample, and 130 participated in the adherence study. Data collection is in process, and the final data analysis is planned to be performed in 2022. CONCLUSIONS The OpTAT study will inform us about the effectiveness of the IMAP program in patients with solid cancers treated with PKIs. It will also shed light on PKI pharmacokinetic and pharmacodynamic properties, with the aim of learning how to adapt the PKI dosage at the individual patient level to increase PKI clinical suitability. The IMAP program will enable interprofessional teams to learn about patients’ needs and to consider their concerns about their PKI self-management, considering the patient as an active partner. CLINICALTRIAL ClinicalTrials.gov NCT04484064; https://clinicaltrials.gov/ct2/show/NCT04484064. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/30090

Compared with the general population, oncology patients face a higher morbidity and mortality caused by the COVID-19 pandemic. As a result, health systems had to quickly adapt cancer care in order to maintain the best quality and patient safety. From March to May and from October to December 2020, 254 patients diagnosed with cancer and tested positive for SARS-CoV-2 benefited from a tele-health monitoring at the Oncology Department at CHUV. This article describes the key points of the development, implementation and operation of this tele-health monitoring, enabled by an interdisciplinary and inter-professional collaboration between different units and healthcare professionals.En comparaison de la population générale, les patients oncologiques font face à une augmentation de leur morbimortalité en lien avec la pandémie de Covid-19. Par conséquent, les systèmes de santé ont dû s’adapter rapidement dans ce contexte instable afin de poursuivre des soins de qualité tout en assurant la sécurité des patients. De mars à mai ainsi que d’octobre à décembre 2020, un total de 254 patients oncologiques testés positifs au SARS-CoV-2 ont bénéficié d’un suivi téléphonique au Département d’oncologie du CHUV. Cet article décrit les points clés de l’implantation et du fonctionnement de ce télésuivi, grâce à la collaboration entre différentes unités et une équipe interprofessionnelle.

The COVID-19 pandemic that has swept around the world in early 2020 has changed our daily practice and habits. Fortunately, however, 2020 also brings its share of new approaches and therapeutic combinations as well as new therapies. These advances are improving the outcomes and quality of life of our patients across the spectrum of oncological diseases. This article summarises the latest oncological advances and novelties for 2020 in the following tumor entities : lung, breast, digestive, gynecological, urological and ENT.La pandémie de Covid-19 survenue début 2020 dans le monde entier aura bouleversé notre pratique quotidienne et nos habitudes. Heureusement, sur le plan thérapeutique, l’année 2020 apporte également son lot de nouvelles approches et combinaisons thérapeutiques ainsi que l’introduction de nouvelles molécules, permettant d’améliorer le pronostic vital et la qualité de vie de nos patients, dans de nombreux domaines. Cet article résume les dernières avancées et nouveautés oncologiques de l’année 2020 dans les domaines suivants : poumon, sein, sphère digestive, gynécologique, urologique et ORL.

BACKGROUND Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy but frequently cause immune-related adverse events (irAEs). Description of late-onset and duration of irAEs in the literature is often incomplete. METHODS To investigate reporting and incidence of late-onset and long-lasting irAEs, we reviewed all registration trials leading to ICI's approval by the US FDA and/or EMA up to December 2019. We analysed real-world data from all lung cancer (LC) and melanoma (Mel) patients treated with approved ICIs at the University Hospital of Lausanne (CHUV) from 2011 to 2019. To account for the immortal time bias, we used a time-dependent analysis to assess the potential association between irAEs and overall survival (OS). RESULTS Duration of irAEs and proportion of patients with ongoing toxicities at data cut-off were not specified in 56/62 (90%) publications of ICIs registration trials. In our real-world analysis, including 437 patients (217 LC, 220 Mel), 229 (52.4%) experienced at least one grade ���2 toxicity, for a total of 318 reported irAEs, of which 112 (35.2%) were long-lasting (���6 months) and about 40% were ongoing at a median follow-up of 369 days [194-695] or patient death. The cumulative probability of irAE onset from treatment initiation was 42.8%, 51.0% and 57.3% at 6, 12 and 24 months, respectively. The rate of ongoing toxicity from the time of first toxicity onset was 42.8%, 38.4% and 35.7% at 6, 12 and 24 months. Time-dependent analysis showed no significant association between the incidence of irAEs and OS in both cohorts (log Rank p��=��0.67 and 0.19 for LC and Mel, respectively). CONCLUSIONS Late-onset and long-lasting irAEs are underreported but common events during ICIs therapy. Time-dependent survival analysis is advocated to assess their impact on OS. Real-world evidence is warranted to fully capture and characterise late-onset and long-lasting irAEs in order to implement appropriate strategies for patient surveillance and follow-up.

Small cell lung cancer is a recalcitrant malignancy with 5-year survival rates of less than 20%. In the majority of cases, patients have metastatic disease at diagnosis despite the new screening method by low-dose CT-scan. The high throughput sequencing has deepened our understanding of its biology. While the treatment of localized disease has changed little, the arrival of immune checkpoint inhibitors have revolutionized the management of extensive disease. At the same time, new strategies involving certain potential genetic targets are being analyzed on a large scale that could become valuable therapeutic alternatives in the future. Radiation therapy remains a very useful therapeutic modality in all stages of the disease. This article aims to review the epidemiology, molecular pathology, management and innovative therapies in small-cell lung cancer.Le cancer pulmonaire à petites cellules (CPPC) est une tumeur récalcitrante avec une survie à 5 ans de moins de 20 %. Il est fréquemment découvert à un stade métastatique malgré le nouveau dépistage par

In patients with primary or secondary lung tumour treated with immune checkpoint inhibitors, immune-related pneumonitis is a rare adverse event but may evolve to respiratory failure. Prompt management is required and usually consists of treatment interruption and immunosuppressive drug administration. The aim of this study was to evaluate relationships between immune-related pneumonitis and pre-existing parenchymal status, especially tumour location and history of chest radiotherapy. Computed tomography (CT) scans of patients with immune-related pneumonitis were retrospectively reviewed. Pattern, distribution and extent of pneumonitis were assessed in six lung regions. In patients who received radiotherapy, the extent of pneumonitis was evaluated according to the radiation field. Among 253 patients treated with immunotherapy, 15 cases of immune-related pneumonitis were identified. 10 had previous or concomitant chest radiotherapy in addition to immunotherapy. At CT scan, 29 (33%) out of 88 regions encompassed the primary tumour (n=4), a lung metastasis (n=4) and/or radiation fields (n=21). A significantly higher prevalence of parenchymal involvement by immune-related pneumonitis occurred within areas of primary or metastatic malignancy and/or radiation field (97%) as compared to other areas (3%, p=0.009). Lung regions affected by the primary tumour, metastasis or radiotherapy had a higher probability of immune-related pneumonitis than others (OR 10.8, p=0.024). An organising pneumonia (OP) pattern was more frequent after radiotherapy (70% versus 0%, p=0.024), whereas nonspecific interstitial pneumonia features were more commonly seen in radiotherapy-naive patients (100% versus 10%, p=0.002). In patients with primary or secondary lung tumour treated with immune checkpoint inhibitors, immune-related pneumonitis is preferentially located within lung areas involved by tumour and/or radiation fields., In patients with primary or secondary lung tumour treated by immune checkpoint inhibitors, immune-related pneumonitis induced by these agents is preferentially located within lung areas involved by tumour and/or radiation fields http://bit.ly/2NJZmGx

Introduction There is no approved second-line treatment for malignant pleural mesothelioma (MPM). On the basis of promising early results, pembrolizumab was used off-label in Switzerland and Australia. We investigated outcomes in association with clinicopathological features and expression of programmed death ligand 1 (PD-L1). Methods Registry data in Australia and Switzerland were pooled. Patient characteristics, including age, sex, histological subtype, and previous treatments were captured. Outcomes were assessed locally. PD-L1 expression was categorized as negative ( Results A total of 93 patients (48 from Switzerland and 45 from Australia) were treated; 68 patients (73%) had epithelioid MPM, and 67 (72%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Pembrolizumab was the second-line treatment in 48 of 93 patients (52%). PD-L1 expression results were available for 66 patients (71%). Most (68%) were negative, 18% were intermediate, and 14% were high for PD-L1 expression. In the full cohort, the overall response rate (ORR) was 18%, the median progression-free survival (mPFS) was 3.1 months, and the median overall survival was 7.2 months. In patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 and only one previous systemic treatment (n = 35), the ORR was 37%, the mPFS was 3.7 months, and the median overall survival was 10.2 months. The nonepitheloid histological subtype showed an improved ORR (24% versus 16% [p = 0.54) and mPFS (5.6 versus 2.8 months [p = 0.02]). Compared with intermediate and negative PD-L1 expression, high PD-L1 expression was associated with an improved ORR (44% versus 42% versus 11% [p = 0.01]) and mPFS (6.2 versus 3.9 versus 2.7 months [p = 0.04]). Toxicity was as expected. Conclusion These real-world data demonstrate similar response rates but inferior survival compared with those in early-phase trials. High PD-L1 expression and nonepitheloid histological subtype were associated with greater activity. Anti–PD-L1 immunotherapy is a reasonable second-line therapy in patients with MPM.

International audience; Purpose In the context of locally advanced oropharyngeal cancer (LAOC) treated with definitive radiotherapy (RT) (combined with chemotherapy or cetuximab), the aims of this study were: (1) to identify PET-FDG parameters correlated with overall survival (OS) from a first cohort of patients; then (2) to compute a prognostic score; and (3) finally to validate this scoring system in a second independent cohort of patients. Materials and methods A total of 76 consecutive patients (training cohort from Rennes) treated with chemoradiotherapy or RT with cetuximab for LAOC were used to build a predictive model of locoregional control (LRC) and OS based on PET-FDG parameters. After internal calibration and validation of this model, a nomogram and a scoring system were developed and tested in a validation cohort of 46 consecutive patients treated with definitive RT for LAOC in Lausanne. Results In multivariate analysis, the metabolic tumour volume (MTV) of the primary tumour and the lymph nodes were independent predictive factors for LRC and OS. Internal calibration showed a very good adjustment between the predicted OS and the observed OS at 24 months. Using the predictive score, two risk groups were identified (median OS 42 versus 14 months, p

e15095 Background: ICIs are effective in many tumors, but can cause severe irAEs, with potential long-term impact. Description of irAEs in literature is often insufficient, especially in terms of irAEs duration, and in terms of incidence of late-onset events. Namely, duration of irAEs and proportion of patients (pts) with toxicity still ongoing at data cut-off were not specified in 52 (89.6%) of 58 publications of trials leading to ICIs approval by US FDA and/or EMA up to August 2019. Real-world data are urgently needed to integrate this information. Methods: We retrieved the medical charts of all pts affected by lung cancer (LC) and melanoma (Mel) treated consecutively with approved ICIs at the Centre Hospitalier Universitaire Vaudoise (CHUV) from Jan 2012 to Dec 2019. We collected the following data: treatment setting, ICIs received, duration of each treatment, incidence of any irAEs of grade (G) ≥ 2 (according to CTCAE v5.0), time to onset and duration of irAEs. Pts with follow-up (FU) ≤ 28 days were excluded. Results: 345 pts were included (166 LC, 179 Mel), for a total of 455 ICIs treatment lines. 33 pts (7%, all with Mel) were treated in the adjuvant setting, while all the others were treated for advanced disease. 228 pts (50%) received anti-PD1, 43 (9%) anti-PD-L1, 56 (12%) anti-CTLA-4, 100 (22%) ICI-ICI combinations and 28 (6%) ICI–chemotherapy combinations. Median FU was 369 days (range 29-2903). Median duration of treatment was 71 days (range 1-1625). 196 pts (57%) experienced at least 1 G≥2 irAE for a total of 277 irAEs (22% skin, 18% gastro-intentinal [GI], 13% pneumonitis, 12% thyroid disorders, 11% hyphophisitis and 8% hepatitis). With 122/277 (44%) irAEs still on-going at our data cut-off, median duration of irAEs was 98 days; 104/277 irAEs (37%) lasted more than 6 month, of them 89% were considered irreversible. Out of 76 pts still on ICIs treatment at 6 months, incidence of G≥2 irAE with onset after 6 months was 51% (26% pneumonitis, 26% endocrine disorders, 15% skin disorders, 8% hepatitis and GI). Out of 32 pts still on ICIs treatment at 12 months, incidence of G≥2 irAE with onset after 12 months was 41% (38% pneumonitis, 23% endocrine and 15% skin disorders, 8% hepatitis and GI). Conclusions: Our real-world analysis shows that long-lasting and late-onset irAEs represent an important issue during ICIs treatment. A better description of toxicities in clinical trials is needed to allow a proper evaluation of treatment value and the impact on patients' quality of life.

Highlights • Radiation recall phenomenum. • Radiation recall dermatitis. • The observation suggested a threshold dose for the occurrence of the recall effect., Radiation recall is a rare phenomenon that can be observed in the field of radiotherapy, months or years after irradiation when a patient is exposed to certain pharmaceutical agents. In this report, we relate a case of radiation recall dermatitis induced after the application of a topical natural cream, 2 years after the initial radiotherapy treatment. Skin reactions were severe and limited to the irradiated volume, whereas a large part of the skin where the cream was applied outside the radiation field was strictly normal. More precisely, the radiation recall dermatitis matched with the isodose 20 Gy, whereas no recall reaction was observed in the lower dose areas (5, 10 or 15 Gy) despite these areas were also largely exposed to the cream. In conclusion, this is the first report that could provide a threshold dose for the occurrence of a radiation recall dermatitis, which was not observed below 20 Gy, in the context of this topical reagent.

Background The strengthening or substitution of intravenous cytotoxic chemotherapy cycles by oral targeted anticancer therapies, such as protein kinase inhibitors (PKIs), has provided impressive clinical benefits and autonomy as well as a better quality of life for patients with cancer. Despite these advances, adverse event management at home and medication adherence remain challenging. In addition, PKI plasma concentrations vary significantly among patients with cancer receiving the same dosage, which could explain part of the observed variability in the therapeutic response. Objective The aim of this optimizing oral targeted anticancer therapies (OpTAT) study is to optimize and individualize targeted anticancer treatments to improve patient care and self-monitoring through an interprofessional medication adherence program (IMAP) combined with measurement PKI plasma concentrations. Methods The OpTAT study has two parts: (1) a 1:1 randomized medication adherence program, in which the intervention consists of regular motivational interviewing sessions between the patient and the pharmacist, along with the delivery of PKIs in electronic monitors, and (2) a systematic collection of blood samples and clinical and biological data for combined pharmacokinetic and pharmacodynamic analysis. On the basis of the electronic monitor data, medication adherence will be compared between groups following the three operational definitions: implementation of treatment during the persistent period, persistence with treatment and longitudinal adherence. The implementation will be described using generalized estimating equation models. The persistence of PKI use will be represented using a Kaplan-Meier survival curve. Longitudinal adherence is defined as the product of persistence and implementation. PKI pharmacokinetics will be studied using a population approach. The relationship between drug exposure and efficacy outcomes will be explored using Cox regression analysis of progression-free survival. The relationship between drug exposure and toxicity will be analyzed using a pharmacokinetic-pharmacodynamic model and by logistic regression analysis. Receiver operating characteristic analyses will be applied to evaluate the best exposure threshold associated with clinical benefits. Results The first patient was included in May 2015. As of June 2021, 262 patients had participated in at least one part of the study: 250 patients gave at least one blood sample, and 130 participated in the adherence study. Data collection is in process, and the final data analysis is planned to be performed in 2022. Conclusions The OpTAT study will inform us about the effectiveness of the IMAP program in patients with solid cancers treated with PKIs. It will also shed light on PKI pharmacokinetic and pharmacodynamic properties, with the aim of learning how to adapt the PKI dosage at the individual patient level to increase PKI clinical suitability. The IMAP program will enable interprofessional teams to learn about patients’ needs and to consider their concerns about their PKI self-management, considering the patient as an active partner. Trial Registration ClinicalTrials.gov NCT04484064; https://clinicaltrials.gov/ct2/show/NCT04484064. International Registered Report Identifier (IRRID) DERR1-10.2196/30090

The year 2018 has been incredibly prolific regarding novelties. Several studies have given impressive results and offer new anticancer perspectives. Immunotherapy is gaining more and more place defining a new standard of care for different types of cancer. In parallel with a new approach combining immunotherapy and chemotherapy that is emerging, new forms of adoptive immunotherapy are on the path of approval by regulatory authorities. At the decision-making level, a large somatic genetic analysis is becoming dominant, whereas the addition of more specific biomarkers is still needed regarding immunotherapy. This article aims to summarize the significant new developments in oncology for 2018 concerning the five most common cancers and adoptive cellular immunotherapy.L’année 2018 a été extrêmement prolifique en termes de nouveautés. Plusieurs études ont amené des résultats intéressants et offrent de nouvelles perspectives anticancéreuses. L’immunothérapie prend de plus en plus de place définissant un nouveau standard pour le traitement des différents types de cancer. En parallèle d’une nouvelle approche combinant l’immunothérapie et la chimiothérapie qui voit le jour, des nouvelles formes d’immunothérapie adoptive se situent sur la voie d’approbation par les autorités réglementaires. Sur le plan décisionnel, l’analyse génétique somatique large des tumeurs devient prépondérante, alors que l’addition de biomarqueurs plus spécifiques est encore nécessaire concernant l’immunothérapie. Cet article a pour but de résumer les nouveautés majeures survenues en oncologie pour 2018 concernant les cinq cancers les plus fréquents et l’immunothérapie cellulaire adoptive.

Subsolid nodules represent almost 20% of all pulmonary nodules found incidentally at chest computed tomography (CT). Their detection is steadily rising, in parallel with the increasing number of CT scans performed. Subsolid nodules differ from solid lung nodules in several ways: morphology, course of progression, risk of malignancy and prognosis. Although they remain a diagnostic challenge, a good correlation has been established between radiological appearance and histopathology. Whilst 75% of persistent subsolid nodules represent a form of adenocarcinoma, their prognosis is generally excellent when resected. Non-resected subsolid nodules require a long follow-up of 3 to 5 years due to their slow-growing nature and high prevalence of malignancy. Specific guidelines have been published in 2013 and in 2015.Les nodules subsolides représentent près de 20% des nodules pulmonaires découverts fortuitement lors d’un scanner thoracique. Leur détection ne fait qu’augmenter, parallèlement au nombre croissant de scanners réalisés. Ils se distinguent des nodules solides par leur morphologie, leur comportement évolutif, leur risque de malignité et leur pronostic. Ils restent un challenge diagnostique, mais une bonne corrélation entre les présentations radiologiques et histologiques a été démontrée. Bien que 75% des nodules subsolides persistants soient une forme d’adénocarcinome, leur pronostic est en général excellent après résection. Un suivi prolongé de 3 à 5 ans est requis pour les nodules subsolides non opérés, étant donné leur croissance lente et la haute prévalence de malignité. Des recommandations spécifiques ont été publiées en 2013 et 2015.

BRAF inhibitory therapy is the mainstream treatment for BRAF mutant advanced melanoma. However vemurafenib, a type I mutant BRAF V600 inhibitor, induces an array of proliferative skin disorders from keratosis pilaris-like and keratoacanthoma-like lesions to locally aggressive cutaneous squamous cell carcinoma (cuSCC). Dual BRAF/MEK inhibition is known to lower the incidence of such manifestations, but it is not known whether it can counteract established lesions. Here we show, for the first time, a dramatic response and a restitution ad integro upon dual inhibition of a widespread proliferative affection induced by BRAF monotherapy. A 75-year-old woman was diagnosed with a BRAF V600E mutated metastatic melanoma. Following dacarbazine (DTIC) and ipilimumab, the patient was started on 960 mg twice daily vemurafenib (Zelboraf), which resulted in complete response, but the patient also developed grade IV skin toxicity. Despite dose-reduction to 720 mg twice daily the side effects persisted. We hypothesized that a switch to double inhibition of the mitogen-activated protein kinase pathway with dabrafenib and trametinib could lead to improvement of the skin lesions, while preserving tumor control. The patient was closely followed for changes in skin lesions. We witnessed a rapid regression followed by complete disappearance of all side effects of vemurafenib except for grade I fatigue. The biopsied skin lesions show regression of established keratoacanthoma-like lesions with signs of apoptosis. Switching from the current standard of care vemurafenib therapy to the double BRAF/MEK inhibition in BRAF mutant melanoma patients results in rapid disappearance of established proliferative skin disorders.

Autoimmune side effects are frequent in patients with cancer treated with immune checkpoint–targeting antibodies, but are rare with cancer vaccines. Here, we present a case report on a patient with metastatic melanoma who developed pulmonary sarcoid–like granulomatosis following repetitive vaccinations with peptides and CpG. Despite multiple metastases, including one lesion in the brain, the patient is alive and well more than 13 years after the diagnosis of metastatic disease. The strongly activated tumor-specific CD8+ T cells showed robust long-term memory and effector functions. It is possible that long-term survival and adverse autoimmune events may become more common for vaccines inducing robust anticancer immune responses as were present in this patient. Cancer Immunol Res; 2(12); 1148–53. ©2014 AACR.

Introduction: To presents the outcomes of our technique for medically inoperable both primary and secondprimary (SPLC) early stages non-small-cell lung cancer and to integrate the possibility of organising pneumonia (OP) within the irradiation field (IF) by the analysis of radiological changes. Materials and Methods: Retrospective analysis after the one-year (2011-2012) experience in our hospital. Seventeen patients were treated with the same delivery plan using tomotherapy as a total dose of 60 Gy in 5 fractions. Outcomes and toxicities were recorded and, for SPLC, were described separately. A single radiologist reviewed computed tomography scans. Results: Sixteen patients were included; five primary lung malignancies (31.3%), 10 SPLC (62.5%) and 1 isolated mediastinal metastasis of lung cancer (6.2%). A pathological proof was obtained for 72.2% of all lesions. The median radiological follow-up was 11.0 (10.5 months for SPLC). For all cases the 6and 12-months survival rates were 100% and 77.7% (100% and 71.4% for SPLC), and the 6and 12months loco-regional control rates counted both for (similarly to SPLC) 100%. Two of 16 patients developed grade 3 late transient (after steroids therapy) radiation pneumonitis and one presented asymptomatic infiltrates as comparable to OP opacities. Conclusions: The T-SBRT was safe and effective. Mild OP could probably be associated to radiation-induced anomalies into the IF and the knowledge of the possibility of migrating opacities, could help to discern relapse to radiation-induced opacities.

IMPORTANCE There are limited comparative data on the durability of neutralizing antibody (nAb) responses elicited by messenger RNA (mRNA) vaccines against the SARS-CoV-2 variants of concern (VOCs) in immunocompromised patients and healthy controls., OBJECTIVE To assess the humoral responses after vaccination with BNT162b2 (Pfizer- BioNTech) or mRNA-1273 (Moderna) vaccines., DESIGN, SETTING, AND PARTICIPANTS In this prospective, longitudinal monocentric comparative effectiveness study conducted at the Lausanne University Hospital, binding IgG anti-spike antibody and nAb levels were measured at 1 week, 1 month, 3 months, and 6 months after vaccination with mRNA-1273 (24.6% of participants) or BNT162b2 (753% of participants)., INTERVENTIONS All participants received 2 doses of either mRNA-1273 or BNT162b2 vaccines 4 to 6 weeks apart., MAIN OUTCOMES AND MEASURES The primary outcome of the study was the persistence of nAb responses against the original, nonvariant SARS-CoV-2 (2019-nCoV) and different VOCs at 6 months after vaccination. Key secondary outcomes were associations of the type of mRNA vaccine, the underlying disease, and the treatment with the response to vaccination., RESULTS Among the 841 participants enrolled between January 14 and August 8, 2021, the patient population comprised 637 participants (mean [SD] age, 61.8 [13.7] years; 386 [60.6%] female), and the healthy control population comprised 204 participants (mean [SD] age, 45.9 [12.0] years; 144 [70.6%] female). There were 399 patients with solid cancers, 101 with hematologic cancers. 38 with solid organ transplants, 99 with autoimmune diseases, and 204 healthy controls. More than 15 000 nAb determinations were performed against the original, nonvariant 2019-nCoV and the Alpha, Beta, Gamma, and Delta variants. The proportions of nAbs and their titers decreased in all study groups at 6 months after vaccination, with the greatest decreases for the Beta and Delta variants. For Beta, the proportion decreased to a median (SE) of 392% (5.5%) in those with hematologic cancers, 44,8% (2.7%) in those with solid cancers, 23.1% (8.3%) in those with solid organ transplants, and 22.7% (4.8%) in those with autoimmune diseases compared with 52.1% (4.2 degrees A.) in healthy controls. For Delta, the proportions decreased to 41.8% (5.6%) in participants with hematologic cancer, 51.9% (2.7%) in those with solid cancers, 26.9% (8.7%) in those with solid organ transplants, and 30.7% (5.3%) in those with autoimmune diseases compared with 56.9% (4.1%) healthy controls. Neutralizing antibody titers decreased 3.5- to 5-fold between month 1 and month 6, and the estimated duration of response was greater and more durable among those participants vaccinated with mRNA-1273. In participants with solid cancers, the estimated duration of nAbs against the Beta variant was 221 days with mRNA-1273 and 146 days with BNT162b2, and against the Delta variant, it was 226 days with mRNA-1273 and 161 with BNT162b2. The estimated duration of nAbs in participants with hematologic cancers was 113 and 127 days against Beta and Delta variants, respectively., CONCLUSIONS AND RELEVANCE This comparative effectiveness study suggests that approximately half of patients with hematologic cancers and solid cancers, about 70% of patients with solid organ transplants or autoimmune diseases, and 40% of healthy controls have lost nAbs against the circulating VOCs at 6 months after vaccination. These findings may be helpful for developing the best boosting vaccination schedule especially in immunocompromised patients.