Real-world safety and efficacy data of immunotherapy in patients with cancer and autoimmune disease: the experience of the Hellenic Cooperative Oncology Group.

BACKGROUND: Data on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with concurrent autoimmune diseases (AID) are limited. METHODS: We performed a retrospective multicenter review of medical records of patients with cancer and underlying AID who received ICI. The primary endpoint was progression-free survival (PFS). RESULTS: Among 123 patients with pre-existing AID who received ICI, the majority had been diagnosed with non-small cell lung cancer (NSCLC, 68.3%) and melanoma (14.6%). Most patients had a rheumatologic (43.9%), or an endocrine disorder (21.1%). Overall, 74 (60.2%) patients experienced an immune-related adverse event (irAE) after ICI initiation, AID flare (25.2%), or new irAE (35%). Frequent irAEs included thyroiditis, dermatitis and colitis. ICI was permanently discontinued due to unacceptable (8.1%) or fatal (0.8%) toxicity. In patients with NSCLC, corticosteroid treatment at the initiation of immunotherapy was associated with poor PFS (HR = 2.78, 95% CI 1.40-5.50, p = 0.003). The occurrence of irAE was associated with increased PFS (HR = 0.48, 95% CI 0.25-0.92, p = 0.026). Both parameters maintained their independent prognostic significance. CONCLUSIONS: ICI in patients with cancer and pre-existing AID is associated with manageable toxicity that infrequently requires treatment discontinuation. However, since severe AID flare might occur, expected ICI efficacy and toxicity must be balanced. CLINICAL TRIAL IDENTIFIER: NCT04805099.

Producing the appropriate model and drug for intratumoural ablation.

Local treatment is necessary for several cancer patients. There are situations where cancer tissue induces locally severe symptoms. Therefore, additional local disease control is necessary. There are two major issues for efficient local treatment: the method of application and the penetration of the drug formulation. We need efficient tools to guide the drug formulation to the target point, and an effective drug formulation that is diffused within the tumour microenvironment with a sustained-release effect.

Acute Effects of a Heat-Not-Burn Tobacco Product on Pulmonary Function.

Background and objectives: During the last decade, conventional tobacco smoking is experiencing a decline and new smoking products have been introduced. IQOS ("I-Quit-Ordinary-Smoking") is a type of "heat-not-burn" (HNB) tobacco product. The impact of IQOS on respiratory health is currently not defined. The objectives of this study were to evaluate the acute effects of IQOS on pulmonary function in non-smokers and current smokers. Materials and Methods: Fifty male healthy non-smokers and current smokers with no known co-morbidity underwent an exhaled CO measurement, oximetry (SaO2%), pulmonary function tests (flows, volumes and diffusion capacity), and a measurement of respiratory resistances with an impulse oscillometry system (IOS) before and immediately after IQOS use. Results: In the whole group of 50 participants, SaO2%, forced expiratory flow at 25% and 50% of vital capacity (FEF 25%, FEF 50%, respectively), peak expiratory flow (PEF), and diffusion lung capacity for carbon monoxide/VA (KCO) decreased significantly after IQOS use, whereas exhaled CO and airway resistance (R5 Hz, R10 Hz, r15 Hz, R20 Hz, R25 Hz, R35 Hz) increased. When the groups of smokers and non-smokers were compared, in both groups (all males, 25 smokers and 25 non-smokers), exhaled CO increased and SaO2% decreased after IQOS use (p < 0.001). In the group of non-smokers, PEF (pre 8.22 ± 2.06 vs. post 7.5 ± 2.16, p = 0.001) and FEF 25% (pre 7.6 ± 1.89 vs. 7.14 ± 2.06, p = 0.009) decreased significantly; respiratory resistances R20 Hz (pre 0.34 ± 0.1 vs. post 0.36 ± 0.09, p = 0.09) and R25 Hz (pre 0.36 ± 0.1 vs. post 0.38 ± 0.09, p = 0.08) increased almost significantly. In smokers, PEF (pre 7.69 ± 2.26 vs. post 7.12 ± 2.03, p = 0.007) and expiratory reserve volume (ERV) (pre 1.57 ± 0.76 vs. post1.23 ± 0.48, p = 0.03) decreased and R35 Hz (pre 0.36 ± 0.11 vs. post 0.39 ± 0.11, p = 0.047) increased. The differences in the changes after the use of IQOS did not differ between groups. Conclusions: IQOS had an impact on exhaled CO, SaO2%, and airways function immediately after use. Even though these changes were rather small to be considered of major clinical importance, they should raise concerns regarding the long-term safety of this product. Further research is needed for the short- and long-term effects of IQOS, especially in patients with respiratory disease.

Comparison of Laryngoscopic Views betweenC-MAC™ and Conventional Laryngoscopy in Patients with Multiple Preoperative Prognostic Criteria of Difficult Intubation. An Observational Cross-Sectional Study.

Background and Objectives: Video laryngoscopy has been proven useful under difficult airway scenarios, but it is unclear whether anticipated improvement of visualization is related to specific difficult intubation prognostic factors. The present study evaluated the change in laryngoscopic view between conventional and C-MAC® laryngoscopy and the presence of multiple difficult intubation risk factors. Materials and Methods: Patients scheduled for elective surgery with >2 difficult intubation factors, (Mallampati, thyromental distance (TMD), interinscisor gap, buck teeth, upper lip bite test, cervical motility, body mass index (BMI)) were eligible. Patients underwent direct laryngoscopy (DL) followed by C-MAC™ laryngoscopy (VL) and intubation. Change of view between DL and VL, time for best view, intubation difficulty scale (IDS) and correlation between prognostic factors, laryngoscopic view improvement, and IDS were measured. Results: One-hundred and seventy-six patients completed the study. VL lead to fewer Cormarck-Lehane (C/L) III-IV, compared to DL (13.6% versus 54.6%, p < 0.001). The time to best view was also shorter (VL: 10.82 s, DL: 12.08 s, p = 0.19). Mallampati III-IV and TMD ≤ 6 cm were related to improvement of C/L between DL and VL. Logistic regression showed these two factors to be a significant risk factor of the glottis view change (p = 0.006, AUC-ROC = 0.57, 95% CI: 0.47-0.66). 175/176 patients were intubated with VL. 108/176 were graded as 0 < IDS ≤ 5 and 12/176 as IDS > 5. IDS was only correlated to the VL view (p < 0.0001). Conclusion: VL improved laryngoscopic view in patients with multiple factors of difficult intubation. Mallampati and TMD were related to the improved view. However, intubation difficulty was only related to the VL view and not to prognostic factors.

Pharmacologic and Non-Pharmacologic Interventions for HIV-Neuropathy Pain. A Systematic Review and a Meta-Analysis.

Background and Objectives: Among HIV infection symptoms, sensory neuropathy (HIV-SN) remains a main cause of suffering, with incidence varying from 13-50%. So far, numerous pharmacological and non-pharmacological treatments have been tested, although few evidence-based analgesic options are available. We conducted an up-to-date systematic review and meta-analysis of the literature in order to evaluate the efficacy and safety of pharmacologic and non-pharmacologic treatments for pain control, in patients with HIV neuropathy. Materials and Methods: We searched MEDLINE, EMBASE, Scopus/Elsevier, The Cochrane Central Register of Controlled Trials (CENTRAL), USA Clinical Trials registry, and The International Web of Science up to April 2019. All randomized controlled trials evaluating efficacy and safety of non-pharmacologic and pharmacologic therapies were included. Efficacy was defined as pain reduction during the study period. Safety was estimated from adverse events. A meta-analysis was performed whenever possible. Results: 27 randomized controlled trials (RCTs) were included for analysis (7 evaluating non pharmacologic interventions, 20 pharmacologic therapies). Non-pharmacologic studies (n = 742) involved seven different therapeutic modalities. Only Acupuncture/Moxibustion showed pain reduction over placebo, Gracely Pain Scale Mean (SD): Acu/Moxa 0.85 (0.12), placebo 1.10 (0.09), p = 0.05. Pharmacologic studies, involving 2516 patients revealed efficacy for capsaicin 8% over placebo (mean difference -8.04 [95% CI: -14.92 -1.15], smoked cannabis (where pooling data for meta-analysis was not possible) and recombinant Nerve Growth Factor. Conclusion: Despite various modalities for pain control in HIV-SN, strongest evidence exists for capsaicin 8% and smoked cannabis, although of low methodological quality. Among non-pharmacologic modalities, only Acu/Moxa gave a marginal beneficial effect in one study, possibly limited by inherent methodological flaws.

Ablation for Single Pulmonary Nodules, Primary or Metastatic. Εndobronchial Ablation Systems or Percutaneous.

Single pulmonary nodules are a difficult to diagnose imagining artifact. Currently novel diagnostic tools such as Radial-EBUS with or not C-ARM flouroscopy, electromagnetic navigation systems, robotic bronchoscopy and cone beam-compuer tomography (CBCT) can assist in the optimal guidance of biopsy equipment. After diagnosis of lung cancer or metastatic disease as pulmonary nodule, then surgery or ablation methods as local treatment can be applied. The percutaneous ablation systems under computed tomography guidance with radiofrequency, microwave, cryo and thermosphere have been used for several years. In the past 10 years extensive research has been made for endobronchial ablation systems and methods. We will present and comment on the two different ablation methods and present up to date data.

Simultaneous Resection for Colorectal and Liver Metastases, new equipment and personalized medicine.

Nowadays we perform synchronous colorectal cancer resection along with synchronous liver metastases. We investigated whether colon resection first is safer than liver resection first and if simultaneous surgeries are in general safe. Patients and Methods: Twenty patients were included in our multicenter study. In our study patients had simultaneous laparoscopic resection of primary colorectal cancer and liver metastases. The patients included were divided into two groups based on their first surgery. Group A had colon resection first (n = 10) and group B had liver resection first (n = 10). All adverse effects and outcomes were compared after the first day of hospitalization. Results: The only difference between the two groups was the operative blood loss. It was observed to be less in group B. Conclusion: In our study we did not observe any significant difference regarding the order of the operation.

Chronic Obstructive Pulmonary Disease and Non-Small Cell Lung Cancer an association.

Objectives: Lung cancer is known to be associated with chronic obstructive pulmonary disease. Moreover; nutritional status is associated with chronic obstructive disease treatment and lung cancer. Our aim was to evaluate the interaction of the COPD status and treatment of non-small cell lung cancer. Methods: Eighty-two patients were enrolled in our multicenter study. Chronic obstructive disease stage, spirometry and treatment was recorded along with the treatment and Body Mass Index (BMI), Mediterranian Diet Score, Pack Years, Basic Metabolsim (RMR) (kcal/day), VO2 (ml/min), Ve (lt/min) and Physical Activity. The statistical analysis was performed using the JMP 14.3 (SAS Inc 2018) software. Results: The drug pairs showed a steady and unchanged by time health condition for 48 patients. Overall, 31 patients were recorded with worse COPD health conditions. The one-way ANOVA clearly indicated that chemotherapy induced the best FEV1-difference conditions with a positive effect of 8.56 mean FEV volume, the combined treatment simply did not have an effect (-0.9), while immunotherapy and patients receiving radiation decreased their FEV1 volume down to -4.23 and -5.15 mean values. Conclusions: Patients receiving chemotherapy alone had their chronic obstructive disease improved with less drugs and exacerbations, while patients receiving immunotherapy had their chronic obstructive disease stable, while all other treatment combinations worsened the patients chronic obstructive disease. Nutritional status did not affect the chronic obstructive disease of these patients in any way.

Adenosquamous carcinoma of the pancreas: two case reports and review of the literature.

BACKGROUND: Among the total reported cases of pancreatic duct adenocarcinomas, around 1-2.9% are adenosquamous carcinomas of the pancreas. Due to limited data, preoperative diagnosis is a great challenge for physicians, and it is usually set post-operational, based on the pathologist report. We operated on two cases of adenosquamous carcinoma of the pancreas, which we present alongside the operation and treatment planning. CASE REPORT: A 69-year-old Caucasian female and a 63-year-old Caucasian male presented themselves with jaundice in our department. The abdomen computed tomography and magnetic resonance imaging scans revealed lesions of the pancreas. A pancreas-duodenumectomy was performed in both patients, and the post-operational histology analysis revealed adenosquamous carcinoma of the pancreas head. The patients were discharged in good condition and received further chemotherapy treatment after surgery. CONCLUSIONS: Two case reports of adenosquamous carcinoma of the pancreas are described here, which both underwent surgery resection. The limited available literature on this topic substantially limits the knowledge and guidance on treatment. A summarization of the available literature is attempted, alongside a description of possible fields of future research.

Cryo-Biopsy versus 19G needle versus 22G needle with EBUS-TBNA endoscopy.

Introduction: We have been using cryo-biopsy for endobronchial lesions for lung cancer diagnosis and debulking. Cryo-biopsy is also known to be an excellent tool for diagnosis of lung interstitial disease. Recently cryo-biopsy with the 1.1mm probe was used for lymphnode biopsy. Patients and Methods: 311 patients participated with lymphadenopathy and at least one lung lesion. The following tools were used for diagnosis; 22G Mediglobe Sonotip, 22G Medigolbe, 21G Olympus, 19G Olympus and 1.1mm cryo probe ERBE CRYO 2 system (3 seconds froze). A PENTAX Convex-probe EBUS was used for biopsy guidance. Results: Cell-blocks slices had a higher number in the 19G needle group (19G> Cryo Probe>22G Mediglobe Sonotip >21G Olympus >22G Mediglobe). Conclusion: Cryo biopsy of the lymphnodes is safe with the 1.1mm cryo probe. Further studies are needed in order to evaluate new probes and the technique specifications.

Nutrition and NSCLC; Should We Administer Food Supplements?

Non-small cell lung cancer is usually diagnosed at the advanced stage of the disease. We have novel diagnostic tools. However, prevention is still the best way to deal with this disease. Patients receive different treatments with different adverse effects. Targeted treatment with tyrosine kinase inhibitors and immunotherapy have entered everyday clinical practice. The nutritional status of a patient plays a crucial role in the treatment of the patient. Cachexia is observed in most cancer patients, and it has been identified as an independent factor in the overall survival of the patient. The improvement of nutritional status and metabolism directly impacts the quality of life, daily living, and overall survival of a lung cancer patient. We conducted a search on PubMed and Scopus and identified relevant publications. In this review, we will focus on the nutritional status of NSCLC patients and how food supplements assist in the QoL based on published literature. Additional information from other cancer types will be included where necessary.

The lengths of trachea and main bronchus in Chinese Shanghai population.

The knowledge of airway length is the theoretical basis in the diagnosis and management of airway disease. The objective of this study is to measure the length of trachea and left and right main bronchus in Chinese Shanghai population. A total of 153 consecutive adult patients with minor pulmonary disease in Xinhua hospital were enrolled for bronchoscopy examination. Measurements were conducted on head and neck neutral position and height, weight and age for each patient were recorded either. Student t test and multiple linear regression was used to compare means between males and females and to analyze correlation among height, weight, sexual dimorphism and the lengths of the trachea and bronchus. The lengths of the trachea and left main bronchus are significantly different between male and female patients (P < 0.01), but not for the lengths of right main bronchus between man and woman. Multiple linear regression analysis showed that height but not sexual dimorphism and weight correlated with the lengths of the trachea and right main bronchus. The lengths of the trachea and left main bronchus are significantly longer in males than in females. Moreover, height but not sexual dimorphism and weight influenced the length of airway.

Bronchogenic cyst or lung cancer. Only biopsy can tell.

Bronchogenic cysts are rare congenital malformations which derive from primitive ventral foregut. They are usually observed in intrathoracically. A fifty year old male was admitted for the investigation of a three month chest pain. Computed tomography scan of the thorax revealed a lesion around the esophagus and left stem bronchus. Endobronchial ultrasound with convex probe and a 19G needle biopsy revealed a bronchogenic cystic which was removed with video assisted thoracic surgery. Initial radiologic assessment although was thought to be lung cancer because of the smoking habit it turned out to be benignancy. EBUS-TBNAB with 10G needle is safe and absolutely necessary for these lesions, as they take large samples.

Interventional bronchoscopy for HPV 16 and 66 with the use of spraying interferon-α (2b) plus bevacizumab and anti-reflux agent.

A fifty year old male was diagnosed with bronchial HPV. He was treated with local interventional treatment argon plasma coagulation and subcutaneous injections bevacizumab. Spraying of the regions followed with a specially designed catheter with interferon-α (2b). Systematic treatment of esomeprazole was also administered. After six months the patient is disease free and on close follow-up.

Personalized Approach to Tissue and Liquid Biopsy after Failure of First-Line EGFR-TKIs: Is There an Issue When Tissue Is Not the Issue? A Case Series.

Traditionally, tissue availability from rebiopsy is a prerequisite for adequate sequencing of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in therapy for advanced-stage lung cancer. Tissue biopsy truly is the gold standard for genetic analyses, but in some cases, such as with inadequate localization of the lesion or a patient's inadequate performance status, comorbidities, or unwillingness to undergo an invasive procedure, liquid biopsy-based ctDNA analysis can be a noninvasive alternative approach. However, in some cases the gold standard might not shine that much. It is known that tumor heterogeneity or an inadequate amount of tissue might significantly interfere with the results of testing. In this paper, we present cases of patients with a negative tissue biopsy but a positive liquid biopsy which identified coexisting T790M mutation. These results enabled adequate sequencing and treatment with third-line EGFR-TKIs. Such possibilities stress the need to individualize testing for driver mutations in cases where it is clinically highly indicated.

Biopsy and re-biopsy for PD-L1 expression in NSCLC. association between PD-L1 and checkpoint inhibitor efficacy through treatment in NSCLC. A pilot study.

INTRODUCTION: Lung cancer is diagnosed at a late stage due to lack of early disease symptoms. Therefore an efficient treatment is necessary for prolonged disease free survival. PATIENTS AND METHODS: In our study we recruited 124 patients NSCLC patients with adenocarcinoma and squamus cell carcinoma. All recuited patients had Programmed death-ligand 1 expression ≥50 (PD-L1)with DAKO technique. Immunotherapy was administered with as first line treatment. Re-biopsies were performed in the main lung lesion every 4 months with the restaging of the patient and also in the metastastic sites in other organs that occurred during treatment. PD-L1 expressed was evaluated in the biopsies of the metastatic sites. RESULTS: It appears thereafter that the PD-L1 expression could easily be claimed as a promising bio-index with a cutoff value 65, below which a negative prognosis of the disease progress will be evident and above that value a positive continuation of the disease will be prominent. CONCLUSION: The findings of this study suggest that the PD-L1-65 index works adequately either concerning the neo-metastatic sites or the patient disease responses. Re-biopsies in new metastastic sites are necessary since we probably have a new cancer and chemotherapy should be added. More studies should confirm are results and change the NSCLC treatment approach of these patients.

Responses to SARS-CoV-2 Vaccination in Patients with Cancer (ReCOVer Study): A Prospective Cohort Study of the Hellenic Cooperative Oncology Group.

Data on the effectiveness and safety of approved SARS-CoV-2 vaccines in cancer patients are limited. This observational, prospective cohort study investigated the humoral immune response to SARS-CoV-2 vaccination in 232 cancer patients from 12 HeCOG-affiliated oncology departments compared to 100 healthcare volunteers without known active cancer. The seropositivity rate was measured 2-4 weeks after two vaccine doses, by evaluating neutralising antibodies against the SARS-CoV-2 spike protein using a commercially available immunoassay. Seropositivity was defined as ≥33.8 Binding-Antibody-Units (BAU)/mL. A total of 189 patients and 99 controls were eligible for this analysis. Among patients, 171 (90.5%) were seropositive after two vaccine doses, compared to 98% of controls (p = 0.015). Most seronegative patients were males (66.7%), >70-years-old (55.5%), with comorbidities (61.1%), and on active treatment (88.9%). The median antibody titers among patients were significantly lower than those of the controls (523 vs. 2050 BAU/mL; p < 0.001). The rate of protective titers was 54.5% in patients vs. 97% in controls (p < 0.001). Seropositivity rates and IgG titers in controls did not differ for any studied factor. In cancer patients, higher antibody titers were observed in never-smokers (p = 0.006), women (p = 0.022), <50-year-olds (p = 0.004), PS 0 (p = 0.029), and in breast or ovarian vs. other cancers. Adverse events were comparable to registration trials. In this cohort study, although the seropositivity rate after two vaccine doses in cancer patients seemed satisfactory, their antibody titers were significantly lower than in controls. Monitoring of responses and further elucidation of the clinical factors that affect immunity could guide adaptations of vaccine strategies for vulnerable subgroups.

Connection between PD-L1 expression and standardized uptake value in NSCLC: an early prognostic treatment combination.

Objectives: Lung cancer is still diagnosed at advanced stage and early treatment initiation is needed. Therefore, we need biomarkers or clusters of information that can provide early treatment prognosis.Methods: Biopsies were acquired from 471 patients-lung masses with CT-guided biopsy, convex probe transthorasic biopsy, and EBUS-TBNA convex probe with 18 G needles and 19 G needles.Results: Standardized uptake value (SUV) measurement is associated with female, smoking status, hepatic metastasis, adenocarcinoma and programmed death-ligand 1 (PD-L1). In specific we expect that SUV ≥ 7 is associated with PD-L1 ≥ 50.Conclusions: Lung masses indifferent of size that have SUV ≥ 7 will also have PD-L1 expression ≥ 50. Also, it is likely that these patients will be female with intense smoking habit and hepar or multiple metastasis.

Thyroid cancer diagnosis with transdermal probe 22G U/S versus EBUS-convex probe TBNA-B 22G and 19G: pros and cons.

INTRODUCTION: Thyroid cancer is usually diagnosed both with imaging techniques and transdermal biopsy. Laboratory tests are also included in the initial work-up. PATIENTS AND METHODS: One hundred and thirty patients were included in our study with pathological imaging findings in the thyroid region. Biopsies were performed with 22 G with transdermal convex probe, EBUS 22 G Mediglobe® needle and 19 G Olympus® needle. We investigated the efficiency and safety of both techniques and identified the best candidates for each method. DISCUSSION: 19 G needle identified cancer types such as; Lymphoma, Medullary thyroid cancer, and Hurthle cell cancer, which we know from previous pathology studies that a larger sample is necessary for diagnosis. No safety issues were observed for both techniques and the EBUS technique produced more cell block material when 22 G needle was compared to transdermal biopsy in peritracheal lesions. CONCLUSION: The method of biopsy should be made based on the size and accessibility of the lesion.

Intratumoral Treatment with Chemotherapy and Immunotherapy for NSCLC with EBUS-TBNA 19G.

Introduction: Immunotherapy is being used for the past five years either as first line or second line treatment with great results. Chemotherapy and radiotherapy have been also used as combination to immunotherapy to further enhance this type of treatment. Intratumoral treatment has been previously proposed as a treatment option for certain non-small cell lung cancer patients. Patients and Methods: We recruited in total seventy four patients with non-small cell lung cancer in their second line treatment who received only chemotherapy in their first line treatment with programmed death-ligand-1 ≤ 50. Only adenocarcinoma or squamous cell carcinoma, and all negative for epidermal growth factor receptor, anaplastic lymphoma kinase, proto-oncogene tyrosine-protein kinase-1 and proto-oncogene B-Raf. Data were first examined with descriptive statistics choosing frequencies for categorical variables and histograms for the continuous ones. Twenty five received only intravenous immunotherapy and forty-nine intravenous cisplatin with immunotherapy. Data were first examined with descriptive statistics choosing frequencies for categorical variables and histograms for the continuous ones. Results: The relationships between changes of performance status and disease progression were examined via a single correspondence analysis. The two-dimensional scores (coordinates) derived from the correspondence analysis were then regressed against the predictors to form distinct splits and nodes obtaining quantitative results. The best fit is usually achieved by lowering exhaustively the AICc criterion and looking in parallel the change of R2 expecting improvements more than 5%. both types of therapy are capable of producing best ameliorative effects, when either the programmed death-ligand-1 expression or parenchymal site in joint with low pack years are present in the sampling data. Conclusions: Intratumoral treatment combination with cisplatin plus immunotherapy indifferent of nivolumab or pembrolizumab combination is an effective choice. In specific for those with endobronchial lesions. Moreover; patients with programmed death-ligand-1 ≥ 50 had their performance status and disease progression improved over the eight month observation.