Prognostic Impact of Paraneoplastic Cushing’s Syndrome in Small-Cell Lung Cancer

Introduction:Paraneoplastic Cushing’s syndrome (CushingPS) in small-cell lung cancer is rare but severe.Methods:We studied 383 patients with small-cell lung cancer diagnosed between 1998 and 2012. Among them, 23 patients had CushingPS, 56 had other paraneoplastic syndrome (OtherPS), and 304 had no paraneoplastic syndrome (NoPS).Results:After comparison of the three groups, we observed that CushingPS patients had more extensive disease: 82.6% versus 67.8% versus 53.3% (p = 0.005), respectively, with more than two metastatic sites: 63.2% versus 15.8% and 24.1% (p ⩽ 0.001), a higher World Health Organization performance status (2–4): 73.9% versus 57.1% versus 43.7% (p = 0.006), greater weight loss (≥10%): 47.8% versus 33.9% versus 16.4% (p ⩽ 0.001), reduced objective response to first-line treatment: 47.6% versus 74.1% versus 71.1% (p = 0.04), and poorer sensitivity to first-line treatment: 19% versus 38.9% versus 48.6% (p = 0.01). NoPS patients, with World Health Organization performance status of 3–4, had extensive disease at diagnosis, with response, sensitivity to first-line treatment, and survival similar to the CushingPS group. At relapse, the CushingPS group had no objective response to second-line treatment versus 25% versus 42.8% in OtherPS and NoPS groups, respectively (p = 0.005). The median survival of CushingPS patients was 6.6 months versus 9.2 months for OtherPS and 13.1 months for NoPS patients (p ⩽ 0.001). CushingPS is a prognostic factor of death (hazard ratio, 2.31; p ⩽ 0.001).Conclusion:CushingPS is the worst form of the paraneoplastic syndromes with particularly extensive tumors. Reduced objective response and sensitivity to first-line treatment and no response to second-line treatment suggest starting palliative care early at first line and exclusively at relapse

RELAY, ramucirumab plus erlotinib versus placebo plus erlotinib in patients with untreated, EGFR-mutated, metastatic non-small cell lung cancer: Europe/United States subset analysis.

Background: In EGFR mutation-positive NSCLC, dual EGFR/VEGFR inhibition compared to EGFR alone increases anti-tumor efficacy. The Phase III RELAY trial demonstrated superior PFS for ramucirumab plus erlotinib (RAM + ERL) over placebo plus erlotinib (PBO + ERL) (HR 0.591 [95% CI 0.461–0.760], p<0.0001). EGFR mutated NSCLC is less prevalent in Western versus Asian patients. This prespecified analysis evaluates efficacy and safety of RAM + ERL in EU and US patients enrolled in RELAY. Patients and Methods: Patients were randomized 1:1 to ERL + RAM (10 mg/kg IV) or PBO Q2W. Treatment continued until unacceptable toxicity or progressive disease. Patients were stratified by geographic region (East Asia vs "other" [EU/US and Canada (EU/US)]). Objectives included PFS, ORR, DoR, OS, PFS2, safety and biomarker analysis. Results: EU/US subset included 113/449 (25.9%) patients (58 RAM + ERL, 55 PBO + ERL). RAM + ERL improved PFS (20.6 vs 10.9 months, HR 0.605 [95% CI: 0.362–1.010]). ORR and DCR were similar, but median DoR was longer with RAM + ERL (18.0 vs 10.1 months, HR 0.527 [95% CI: 0.296–0.939]). OS and PFS2 were immature at data cut-off (censoring rates 81.0–81.8% and 67.3–79.3%, respectively). Most commonly reported Grade ≥3 TEAE for RAM + ERL was hypertension (17 [29.8%]) and for PBO + ERL, dermatitis acneiform (5 [9.1%]). Conclusion: EU/US subset analysis showed improved efficacy outcomes for RAM + ERL and a safety profile consistent with the overall population. Ramucirumab is a safe and effective addition to standard-of-care EGFR-TKI for EGFR mutation-positive metastatic NSCLC

Next-Generation Sequencing Reveals High Concordance of Recurrent Somatic Alterations Between Primary Tumor and Metastases From Patients With Non-Small-Cell Lung Cancer

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COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study

Background: Early reports on patients with cancer and COVID-19 have suggested a high mortality rate compared with the general population. Patients with thoracic malignancies are thought to be particularly susceptible to COVID-19 given their older age, smoking habits, and pre-existing cardiopulmonary comorbidities, in addition to cancer treatments. We aimed to study the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with thoracic malignancies. Methods: The Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry is a multicentre observational study composed of a cross-sectional component and a longitudinal cohort component. Eligibility criteria were the presence of any thoracic cancer (non-small-cell lung cancer [NSCLC], small-cell lung cancer, mesothelioma, thymic epithelial tumours, and other pulmonary neuroendocrine neoplasms) and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms. Patients of any age, sex, histology, or stage were considered eligible, including those in active treatment and clinical follow-up. Clinical data were extracted from medical records of consecutive patients from Jan 1, 2020, and will be collected until the end of pandemic declared by WHO. Data on demographics, oncological history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes were collected. Associations between demographic or clinical characteristics and outcomes were measured with odds ratios (ORs) with 95% CIs using univariable and multivariable logistic regression, with sex, age, smoking status, hypertension, and chronic obstructive pulmonary disease included in multivariable analysis. This is a preliminary analysis of the first 200 patients. The registry continues to accept new sites and patient data. Findings: Between March 26 and April 12, 2020, 200 patients with COVID-19 and thoracic cancers from eight countries were identified and included in the TERAVOLT registry; median age was 68·0 years (61·8-75·0) and the majority had an Eastern Cooperative Oncology Group performance status of 0-1 (142 [72%] of 196 patients), were current or former smokers (159 [81%] of 196), had non-small-cell lung cancer (151 [76%] of 200), and were on therapy at the time of COVID-19 diagnosis (147 [74%] of 199), with 112 (57%) of 197 on first-line treatment. 152 (76%) patients were hospitalised and 66 (33%) died. 13 (10%) of 134 patients who met criteria for ICU admission were admitted to ICU; the remaining 121 were hospitalised, but were not admitted to ICU. Univariable analyses revealed that being older than 65 years (OR 1·88, 95% 1·00-3·62), being a current or former smoker (4·24, 1·70-12·95), receiving treatment with chemotherapy alone (2·54, 1·09-6·11), and the presence of any comorbidities (2·65, 1·09-7·46) were associated with increased risk of death. However, in multivariable analysis, only smoking history (OR 3·18, 95% CI 1·11-9·06) was associated with increased risk of death. Interpretation: With an ongoing global pandemic of COVID-19, our data suggest high mortality and low admission to intensive care in patients with thoracic cancer. Whether mortality could be reduced with treatment in intensive care remains to be determined. With improved cancer therapeutic options, access to intensive care should be discussed in a multidisciplinary setting based on cancer specific mortality and patients' preference

APPORT DE L'ENDOSCOPIE EN AUTO-FLUORESCENCE POUR LE DIAGNOSTIC DES LESIONS PRE-NEOPLASIQUES BRONCHIQUES

GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Profil clinico-biologique des patients atteints d'un syndrome de Cushing paranéoplasique dans le cadre d'un carcinome pulmonaire à petites cellules

Nous avons étudié 783 dossiers des patients atteints de carcinome pulmonaire à petites cellules (CPC), dont 25 (3.19 %) avec un syndrome de Cushing paranéoplasique (SCP). La médiane de survie du groupe SCP est de 4.7 mois. Le SCP se voit surtout dans les formes étendues du CPC, est accompagné d un status de performance altéré. Il est important de traiter le SCP avant l administration du traitement anticancéreux pour essayer de limiter les risques infectieux liés au SCP. La médiane de survie de ce sous-groupe est de 2.9 mois. Une cortisolémie élevée est un facteur de mauvais pronostique au sein de la cohorte SCP. Le SCP influence la survie par le biais de complications infectieuses et métaboliques, il existe une tendance à la chimiosensibilité moins importante de CPC accompagné d un SCP. Il existe une différence statistiquement significative de la survie en fonction de la présentation clinique ou biologique du SCP. Cette différence semble être liée à la vitesse de l imprégnation cortisolique plutôt qu un taux de cortisolémie au disgnostic. La vitesse d'imprégnation et donc de l apparition des complications métaboliques et infectieuses du SCP est plus rapide dans le sous-groupe du SCP à présentation biologique. Le syndrome de Cushing paranéoplasique lorsqu il est présent dans un cadre de carcinome neuroendocrine à petites cellules pulmonaire est un facteur indépendant de mauvais pronostique, au même titre que les facteurs déjà connus comme le sexe masculin, PS altéré, âge avancé, forme étendue du CPC ou une maladie réfractaire au traitement antinéoplasique.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

First- and second-line therapy for advanced nonsmall cell lung cancer.

The objectives for the treatment of advanced nonsmall cell lung cancer are palliative and include improvement of survival, symptom control, quality of life and cost. The level of evidence of these benefits is based on multiple randomised trials and meta-analyses. Cisplatin-based chemotherapy with one of the regimens shown to be effective should be preferred. Carboplatin may be substituted for cisplatin if medical contraindications exist. Nonplatinum-based regimens are indicated as first-line treatment for advanced nonsmall cell lung cancer in patients for whom platinum-based chemotherapy is contraindicated. Single drug chemotherapy may be considered in patients with poor performance status. The choice of the active drugs depends on the patient's medical condition. There is no conclusive evidence that high doses of cisplatin (100-120 mg.m(-2)) provide better results than standard lower doses (50-60 mg.m(-2)) in terms of survival. The optimal duration of chemotherapy is poorly documented in advanced nonsmall cell lung cancer. A minimum of four to six cycles is advised in responding patients. Second-line chemotherapy is now accepted as a standard and should be offered to patients with good performance status and failing platinum-based first-line chemotherapy. Evidence is in favour of docetaxel and in the case of adenocarcinoma and adequate renal function, pemetrexed is recommended.Journal ArticleReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe

Unusually prolonged pemetrexed cytotoxicity in a patient with a lung adenocarcinoma: a case report

Abstract Background We describe a case of pemetrexed toxicities related to reabsorption by an ileal neobladder, which caused prolonged hematotoxicity and nephrotoxicity. Case presentation A 59-year-old white man was diagnosed with metastatic wild-type adenocarcinoma of the upper lobe of his right lung. After a first cycle of cisplatin and pemetrexed, he had unusually prolonged aplasia and acute kidney injury. The prolonged aplasia was caused by pemetrexed reabsorption by the ileal mucosa of the neobladder as pemetrexed was eliminated renally in an active form and is partly lipophilic. Conclusions Pemetrexed may be reabsorbed by the ileal mucosa of the neobladder because of its hydrophobic structure and renal excretion in its active form. Acute urinary retention may maintain this phenomenon. Published data excluded a potential role for cisplatin in this toxicity; furthermore, we could not assess pemetrexed concentrations in the blood or urine as these assay techniques are not validated. Thus, care is needed when giving chemotherapy to patients with a neobladder