Real-world outcomes with durvalumab after chemoradiotherapy in patients with unresectable stage III NSCLC: interim analysis of overall survival from PACIFIC-R.

BACKGROUND: Based on the findings of the PACIFIC trial, consolidation durvalumab following platinum-based chemoradiotherapy (CRT) is a global standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC). An earlier analysis from the ongoing PACIFIC-R study (NCT03798535) demonstrated the effectiveness of this regimen in terms of progression-free survival (PFS). Here, we report the first planned overall survival (OS) analysis. PATIENTS AND METHODS: PACIFIC-R is an observational/non-interventional, retrospective study of patients with unresectable, stage III NSCLC who started durvalumab (10 mg/kg intravenously every 2 weeks) within an AstraZeneca-initiated early access program between September 2017 and December 2018. Primary endpoints are OS and investigator-assessed PFS, estimated using the Kaplan-Meier method. RESULTS: By 30 November 2021, the full analysis set included 1154 participants from 10 countries (median follow-up in censored patients: 38.7 months). Median OS was not reached, and the 3-year OS rate was 63.2% (95% confidence interval 60.3% to 65.9%). Three-year OS rates were numerically higher among patients with programmed death-ligand 1 (PD-L1) expression on ≥1% versus <1% of tumor cells (TCs; 67.0% versus 54.4%) and patients who received concurrent CRT (cCRT) versus sequential CRT (sCRT) (64.8% versus 57.9%). CONCLUSIONS: PACIFIC-R data continue to provide evidence for the effectiveness of consolidation durvalumab after CRT in a large, diverse, real-world population. Better outcomes were observed among patients with PD-L1 TCs ≥1% and patients who received cCRT. Nevertheless, encouraging outcomes were still observed among patients with TCs <1% and patients who received sCRT, supporting use of consolidation durvalumab in a broad population of patients with unresectable, stage III NSCLC.

White Blood Cells in Patients Treated with Programmed Cell Death-1 Inhibitors for Non-small Cell Lung Cancer.

PURPOSE: To investigate whether eosinophils and other white blood cell subtypes could be used as response and prognostic markers to anti-Programmed cell Death-1 or anti-PD-Ligand-1 treatments in non-small cell lung cancer patients. METHODS: We retrospectively analyzed data from the NSCLC patients consecutively treated at our hospital with a PD-1/PD-L1 inhibitor in monotherapy for advanced disease. A total of 191 patients were evaluated at three time-points to investigate any relation between tumor response and WBC counts. RESULTS: Baseline WBC and subtypes did not differ according to the type of response seen under treatment. A higher relative eosinophil count (REC) correlated with more objective responses (p = 0.019 at t1 and p = 0.014 at t2; OR for progression = 0.54 and 0.53, respectively) independently of the smoking status, PD-L1 status, and immune-related toxicity (IRT). Higher REC was also associated with a longer duration of treatment (p = 0.0096). Baseline absolute neutrophil count was prognostic (p = 0.049). At t1 relative lymphocytes, absolute and relative neutrophils, and neutrophil-to-lymphocyte ratio were prognostic (p = 0.044, p = 0.014, p = 0.0033, and p = 0.029, respectively). CONCLUSION: Our results show that in NSCLC patients anti-PD-1/PD-L1 therapy induces an early increase only in blood eosinophils, more prominent in responding patients and independent of the smoking status, PD-L1 status, and IRT. Eosinophils are also associated with a longer duration of treatment. Furthermore, our data support a prognostic role of neutrophils, lymphocytes, and their ratio for NSCLC patients with advanced disease treated with PD(L)-1 blockade.

[Managing of dyspnea in oncology]. / Prise en charge de la dyspnée en oncologie.

The perception of ventilatory effort is common in oncology, especially but not exclusively in the advanced stages of neoplastic disease. Dyspnea is a symptom whose discomfort and anguish it generates in the patient and his/ her entourage require constant management throughout the illness. The first step is to identify and optimize the treatment of comorbidities associated with tumour disease. Relief of respiratory oppression as a symptom requires a multidisciplinary approach. Opiates and benzodiazepines are at the forefront of pharmacological management. The mechanical obstruction that limits ventilatory flow and/or chest ampliation may justify more invasive management, including endoscopic techniques. Oxygen therapy will be considered on a case-by-case basis. Finally, global management includes respiratory revalidation, psychological support and improvement of environmental quality.

La perception d'un effort ventilatoire est fréquente en oncologique en particulier, mais non exclusivement, aux stades avancés de la maladie néoplasique. La dyspnée constitue un symptôme dont l'inconfort et l'angoisse qu'elle génère chez le patient et son entourage nécessitent une prise en charge constante tout au long de la maladie. La première étape est d'identifier et d'optimaliser le traitement des pathologies dyspnéisantes conjointes à la maladie tumorale. Le soulagement de l'oppression respiratoire en tant que symptôme nécessite une approche pluridisciplinaire. Les opiacés et les benzodiazépines sont au premier plan de la prise en charge pharmacologique. La levée d'un obstacle mécanique limitant les débits ventilatoires et/ou l'ampliation thoracique peut justifier des techniques plus invasives, notamment endoscopiques. L'oxygénothérapie sera envisagée au cas par cas. Enfin, la prise en charge globale inclut la revalidation respiratoire, le support psychique et l'amélioration de la qualité de l'environnement.

[Pre-cancerous lung lesions and lung cancer screening]. / Les lésions pulmonaires pré-cancéreuses et le dépistage du cancer pulmonaire.

Lung cancer remains the deadliest cancer. It is the result of genetic aberrations in the cells of the respiratory tract exposed to carcinogenic agents, responsible for their anarchic multiplication. It is necessary to study these abnormalities in order to better understand the early stages and the mechanisms of evolution, thereby to establish new screening, monitoring and treatment strategies. The NELSON study confirms that systematic screening for lung cancer in target populations leads to a reduction in mortality from this disease. Despite this, there is currently no consensus in Belgium between medical experts and politicians for systematic lung cancer screening.

Le cancer pulmonaire reste le cancer le plus mortel. Il est le résultat d'aberrations génétiques au niveau de cellules des voies respiratoires exposées aux agents carcinogènes, responsables de leur multiplication anarchique. Il est nécessaire d'étudier ces anomalies pour mieux comprendre les stades précoces et les mécanismes d'évolution afin d'établir de nouvelles stratégies de dépistage, de suivi et de traitement. L'étude NELSON confirme qu'un dépistage systématique des cancers pulmonaires de populations cibles permet une diminution de la mortalité liée à cette pathologie. Malgré cela, il n'y a, actuellement, pas de consensus en Belgique entre les experts médicaux et le monde politique pour un dépistage systématique du cancer pulmonaire.

[Small cell lung cancer : update of therapy]. / Le cancer pulmonaire à petites cellules : mise au point thérapeutique.

Small cell lung cancer is a malignant tumour with a poor prognosis. Standard treatment of metastatic stages has been a platinum doublet since 1980, but the addition of immunotherapy has improved prognosis. For locally advanced stages, the combination of radio-chemotherapy remains the treatment of choice, with no evidence at present of the value of immunotherapy in consolidation, and for localized stages, surgery is the first-line therapy. Unfortunately, in the second line, we have no other molecule than the topotecan despite several studies. Prophylactic brain irradiation remains debated even if it has been validated in localized forms. Finally, there is hope with targeted therapy following the development of subtypes of small cell lung cancer but studies remain difficult to conduct.

Le cancer pulmonaire à petites cellules est une tumeur maligne de mauvais pronostic. Le traitement standard des stades métastatiques était un doublet à base de sels de platine depuis 1980, mais l'ajout de l'immunothérapie a, quand même, permis d'améliorer le pronostic. Pour les stades localement avancés, l'association d'une radiochimiothérapie reste le traitement de choix, sans évidence actuellement de l'intérêt d'une immunothérapie en consolidation, et pour les stades localisés, la chirurgie. Malheureusement, en deuxième ligne, nous n'avons pas d'autre molécule que le topotécan malgré plusieurs études. L'irradiation cérébrale prophylactique reste débattue, même si elle a été validée dans les formes localisées. Enfin, il existe un espoir avec une thérapie ciblée suite à la mise en évidence de sous-types de cancers pulmonaires à petites cellules, mais les études restent difficiles à mener.

[Non small cell lung carcinoma in never-smokers at the Liege University Hospital : a retrospective cohort study, 2017-2018]. / Cancer pulmonaire non à petites cellules chez les patients non fumeurs au CHU de Liège : étude rétrospective entre début 2017 et fin 2018.

Lung cancer is the third most common cancer in Belgium in 2017 and remains the leading cause of cancer death worldwide. There is no longer any doubt that the main cause of lung cancer is smoking. However, the prevalence of lung cancer in never-smokers has been increasing overtime. Moreover, it is now recognized that the lung cancer of non-smoker patients has very distinct characteristics. In this retrospective cohort study (N = 520), we describe the characteristics of non-smoker patients and their non-small cell lung carcinoma and compare them to those of smokers. The patients included in this study were whose with a new diagnostic of lung cancer made at the Liège University Hospital of Liège over 2 years round. Non small cell lung cancer occurring in never-smokers patients is more often seen in young and very old patients, more frequent in female, essentially adenocarcinoma and often associated with mutations. This work confirms that lung cancer in never-smokers shows different features than lung cancer seen in patients with a smoking history.

Le cancer pulmonaire est le troisième cancer le plus fréquent en Belgique en 2017 et reste la première cause de décès par cancer dans le monde. Il ne fait plus aucun doute que la cause principale de cancer du poumon est le tabagisme. Il est toutefois apparu, ces dernières décennies, que le pourcentage de patients non fumeurs augmente parmi les patients présentant un cancer du poumon. Par ailleurs, il est dorénavant reconnu que le cancer pulmonaire du patient non fumeur présente des caractéristiques bien distinctes. Dans ce contexte, nous présentons une étude rétrospective reprenant les caractéristiques cliniques et néoplasiques de l'ensemble des patients ayant présenté un carcinome pulmonaire non à petites cellules dans notre institution sur une période de 2 ans (N = 520). Les cancers non à petites cellules observés chez les nonfumeurs sont plus fréquents chez les sujets jeunes ou très âgés, plus fréquents dans le sexe féminin, en très grande majorité des adénocarcinomes, et souvent associés à des mutations. Nous confirmons ainsi qu'il s'agit d'un cancer aux caractéristiques différentes des cancers pulmonaires des patients fumeurs.

[Targeted therapies for non-small cell lung cancer : state of the art in 2021]. / Traitements ciblés et cancer bronchique non à petites cellules : le point en 2021.

The majority of non-small cell lung cancers are diagnosed as advanced disease. Subsets of adenocarcinomas and of squamous cell carcinomas in nonsmokers present a molecular aberration leading to tumour survival. Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK) and Repressor Of Silencing1 (ROS1) have been identified and targeted with good efficacy for fifteen years. Newer inhibitors brought even greater efficacy with a generally better tolerability. Other molecular aberrations (Kirsten Rat Sarcoma, Rearranged during Transfection, MET, NeuroTrophic Receptor yrosine kinase) are targets for newly developed, more selective drugs. As more and more patients will benefit from targeted therapies, the identification of molecular aberration is more than ever crucial for optimal lung cancer patient care.

La majorité des cancers pulmonaires non à petites cellules se présentent à un stade avancé. Une faible proportion des adénocarcinomes et des cancers épidermoïdes des non-fumeurs est porteur d'(une) anomalie(s) génétique (s) et moléculaire(s) dont dépend leur survie. Depuis une quinzaine d'années, les anomalies de l'«Epidermal Growth Factor Receptor¼ (EGFR), «Anaplastic Lymphoma Kinase¼ (ALK) et Repressor Of Silencing1 (ROS1) sont connues et ciblées par des inhibiteurs efficaces. De nouvelles générations permettent actuellement d'augmenter leur efficacité thérapeutique pour une toxicité globalement moindre. De nouvelles anomalies («Kirsten Rat Sarcoma¼, «Rearranged during Transfection¼, MET, «NeuroTrophic Receptor tyrosine kinase¼) sont, elles aussi, à présent ciblées de manière efficace. La recherche des anomalies moléculaires dans ces sous-types histologiques est devenue incontournable car elle modifie fondamentalement la prise en charge thérapeutique et le pronostic d'une proportion grandissante de patients.

[How I manage... Malignant pleural mesothelioma in 2019]. / Comment je traite Le mésothéliome pleural malin en 2019.

Malignant pleural mesothelioma is a rare disease originating from mesothelial cells of the pleura and is related to asbestos exposure. The tumor is generally extended at the time of diagnosis and the treatment consists of a systemic palliative therapy. Radical approach is limited to very selected patients and is performed in expert centers but without validated schema. Radiotherapy alone is mainly used in palliative intent. Platinum-based chemotherapy in association with pemetrexed is the frontline standard of care and provides a 12-month overall survival. The addition of bevacizumab, an antiangiogenic drug, shows an improvement in median survival. To date, there is no second-line treatment approved for this disease and therefore inclusion in trials is recommended. Currently, various studies are investigating target therapy, immunotherapy and intrapleural perioperative treatment.

Le mésothéliome pleural malin est une tumeur rare, issue des cellules mésothéliales de la plèvre et liée à un contact avec l'amiante. Au moment du diagnostic, la maladie est souvent de stade avancé et est prise en charge par un traitement systémique palliatif. Un traitement radical est réservé pour de rares cas très sélectionnés, au sein de centres experts et ce, sans qu'aucun schéma de prise en charge ne soit validé. La radiothérapie seule est essentiellement utilisée à titre palliatif antalgique. Le traitement systémique de référence consiste en une chimiothérapie à base de cisplatine et pemetrexed permettant une survie globale de 12 mois. L'ajout à la chimiothérapie d'une thérapie ciblée anti-angiogénique, le bévacizumab, a permis une amélioration significative de la survie. A ce jour, il n'y a pas de traitement de 2ème ligne validé et il est donc recommandé d'inclure les patients dans des études cliniques. Actuellement, de multiples études évaluent des thérapies ciblées, des immunothérapies et des traitements intrapleuraux peropératoires.

[An unusual cause of kidney disease in a diabetic patient]. / Le cas clinique du mois. Piège diagnostique d'une protéinurie chez un patient diabétique.

Diabetic nephropathy is a complication of diabetes that affects 25-40 % of diabetic patients. This complication is usually associated with other microangiopathic disorders. We describe a case of a patient suffering from type 2 diabetes with proteinuria, and no signs of retinopathy. This case allows us to discuss and review different etiologies of proteinuria in diabetic patients, particularly in patients who don't suffer from retinopathy.

La néphropathie diabétique est une complication qui affecte 25 à 40 % des patients diabétiques. Cette complication est classiquement associée à d'autres atteintes microangiopathiques. Nous rapportons ici l'histoire d'un patient diabétique de type 2 présentant une protéinurie sans signes de rétinopathie. Ce cas permet de discuter des différentes étiologies d'une protéinurie chez les patients diabétiques, en particulier chez les patients sans rétinopathie.

[PROGNOSTIC FACTORS IN NON SMALL CELL LUNG CANCER]. / FACTEURS PRONOSTIQUES DU CANCER PULMONAIRE NON À PETITES CELLULES.

Non small cell lung cancer is the most frequent type of lung cancer and its prognosis is still very poor. Relapse is frequent and can be observed even in early stages of the disease, in spite of a surgical management with curative intent. This paper gives an overview of the main prognostic factors, the two most important of which remain the staging and tumor histology. These also determine the therapeutic strategy. Other factors of poor prognosis might also be useful for clinicians, particularly in their decision to refer patients for adjuvant therapies.

[MANAGEMENT OF NON-SMALL CELL LUNG CANCER]. / PRISE EN CHARGE DU CANCER BRONCHIQUE NON À PETITES CELLULES.

Already known as the first cause of mortality in men, non-small cell lung cancer (NSCLC) is nowadays a major cause of cancer-related death in women. Its approach relies on a thorough locoregional and extra-thoracic assessment allowing a precise staging which not only has prognostic value, but also determines the therapeutic options. This review presents the current multidisciplinary strategy agreement or the treatment of NSCLC.

[MANAGEMENT OF THYMIC EPITHELIAL TUMORS]. / PRISE EN CHARGE DES TUMEURS ÉPITHÉLIALES THYMIQUES.

Thymic epithelial tumors (TET) are rare. Their optimal care is still poorly defined because of their rarity and of the resulting difficulty to conceive large clinical trials. This review of the literature presents the current clinical and therapeutic data on this form of tumors and underlines the need for a multidisciplinary approach to advanced stage TET. Three clinical situations can be encountered: encapsuled tumors lead to radical surgery; tumors associated with capsular invasion justify a postoperative radiotherapy; advanced stages require a multimodal treatment by chemotherapy, possibly completed by surgery and adjuvant radiotherapy. Besides systemic chemotherapies, the place of new therapeutic strategies, such as somatostatin analogues and targeted treatments, requires to be defined. Treatment of late stage TET is based upon a multidisciplinary dialogue, ideally by a reference team.

An easier method for percutaneous endoscopic gastrojejunostomy tube placement.

BACKGROUND: The current procedures for percutaneous endoscopic gastrojejunostomy (PEG-J) tube placement require fluoroscopy and are time consuming. We describe a new, simple method. METHODS: Ten patients had a PEG-J tube placed by the new method. After placement of a percutaneous endoscopic gastrostomy (PEG) tube using standard technique, the PEG tube was pushed up to the pylorus to make it easier to place the jejunal tube into the duodenum without looping in the stomach. Fluoroscopy was not used. The position of the tube was confirmed by a plain x-ray film of the abdomen. RESULTS: The mean time required for PEG placement and jejunal tube placement was 9.0 and 8.2 minutes, respectively. In all patients the tip of the jejunal tube was at the ligament of Treitz. In one patient the jejunal tube formed a loop in the duodenum, but this was reduced by spontaneous forward migration. In another patient, the tube migrated back into the stomach after 1 week. CONCLUSION: The method described allows easier PEG-J placement without fluoroscopy.

Ex vivo clinical measurement of the optical penetration depth in digestive tissues.

The optical penetration depth of 120 biopsy samples taken from normal or neoplastic digestive tissues is measured by means of a device which can be used in a clinical environment, is easy to handle and delivers results quickly. It is seen that, at 655 nm, values of the penetration depth are centred around 1.1 mm and that they can vary by roughly a factor of 2 between samples of a given kind of tissue. This latter result suggests performing individual measurements immediately before carrying out photodynamic therapy.

Endoscopic Nd:YAG treatment of superficial gastric carcinoma: experience in 18 Western inoperable patients.

Endoscopic treatment of superficial gastric cancer has been reported to be effective by many Japanese teams. In this study, the Nd:YAG laser was used to treat superficial gastric carcinoma in inoperable Caucasian patients with the aim of obtaining a complete response, i.e., disappearance of the lesion endoscopically and biopsy specimens negative for cancer. Eighteen patients unsuitable for surgery with various endoscopic patterns of superficial gastric cancer were treated with the Nd:YAG laser. The endoscopic pattern was type I in 4 patients, type II in 10 (5 type IIa, 1 type IIb, 2 type IIc, 2 mixed IIa + IIc), and type III in 4. Staging by echoendoscopy was performed in 11 patients (T1N0). Nd:YAG laser destruction of the gastric tumor was performed in all cases, with a mean of 4.4 laser sessions per patient. Tumor response was assessed by endoscopy and biopsy. Follow-up averaged 33 +/- 23 (SD) months. Five patients died of diseases unrelated to gastric cancer. An initial complete response was obtained in 16 (89%) patients after a mean of 1.7 laser sessions; histologic evidence of cancer persisted in 2 patients during the entire follow-up period. Among patients with an initial complete response, recurrence was observed in 2. One of them was successfully re-treated. At the end of the follow-up period, 14 (77.7%) of the 18 patients had a complete tumoral response; only 4 patients had histologic evidence of cancer. In 3 of these 4 patients, pretherapeutic echoendoscopic staging had not been performed. Among the 14 patients exhibiting a complete response, 3 had negative biopsy results more than 5 years after diagnosis. No complications occurred. In gastric cancer classified as T1N0 on the basis of pretherapeutic echoendoscopy, a high tumor response rate and even 5-year disease-free survival can be obtained with endoscopic Nd:YAG laser treatment. Endoscopic laser destruction thus appears to be a valuable therapeutic alternative to surgery in inoperable patients with superficial gastric cancer.

Extracorporeal high-intensity focused ultrasound for VX2 liver tumors in the rabbit.

High-Intensity Focused Ultrasound (HIFU) can produce radical tissue necrosis. We wanted to assess tumor destruction, proliferation, and tumorigenesis after HIFU, in an animal model of hepatic tumor. New Zealand rabbits bearing VX-2 solitary liver tumors were treated with extracorporeal HIFU under ultrasound (US) guidance and standardized conditions. Groups differed only for the administration of either one or two consecutive HIFU procedures. Tissue destruction was assessed by stereomicroscopy and planimetry, cell proliferation was estimated by in vivo intra-arterial injection of 1200 muCi [3H]thymidine, and tumorigenesis was tested by reimplantation of treated or untreated pieces of liver tumors into the thighs of nontumor-bearing animals. Mortality was 0. Tumor destruction rates were 76.3% +/- 16% after one procedure and 94.2% +/- 7.3% after two procedures. Nuclear staining was heavy in control tumors and was absent in treated tumors. Untreated hepatic tumors induced measurable tumors at 3 weeks in thighs of all recipients, 7.8 +/- 2.4 cm3 in volume. Hepatic tumors treated with one HIFU procedure induced tumors in the thigh of recipients in 31.3% of cases (0.47 +/- 0.06 cm3), and those treated with two HIFU procedures induced tumors in 0% even after 8 weeks of follow-up. In conclusion, HIFU allows a noninvasive approach to the destruction of liver tumors in this model, with little toxicity but significant effects on proliferation and tumorigenesis. The repetition of HIFU procedures may improve results.

Long-term survival after photodynamic therapy for esophageal cancer.

BACKGROUND/AIMS: Photodynamic therapy (PDT) has been adapted to the endoscopic treatment of digestive cancer, but its indications and efficacy remain uncertain. The aim of this study was to assess its feasibility in the curative treatment of small esophageal tumors. METHODS: From 1983 to 1991, PDT was used to treat 123 patients with esophageal cancer who were recommended for nonsurgical treatment of squamous cell carcinoma (n = 104) and adenocarcinoma (n = 19). Endoscopic ultrasonography (EUS) was performed in 88 patients; 61 were staged uT1 and 27 were staged uT2. A hematoporphyrin derivative was injected 72 hours before laser irradiation with a 630-nm dye laser. PDT was applied alone in 56 patients and as part of a multimodal protocol in the 67 others. RESULTS: The complete response rate at 6 months was 87%. The 5-year survival rate was 25% +/- 6%, and the 5-year disease-specific survival rate was 74% +/- 5%. The complete response rate and survival rate were not different (1) between the PDT alone and the PDT multimodal treatment groups, (2) between the adenocarcinoma and squamous cell carcinoma groups, and (3) between the uT1 and uT2 EUS groups. PDT-related complications were esophageal stenosis (n = 43) and cutaneous photosensitization (n = 16). CONCLUSIONS: In patients with small esophageal tumors who pose high surgical risk, photodynamic therapy is an effective treatment.