Power of Light: Raman Spectroscopy and Machine Learning for the Detection of Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide, emphasizing the urgent need for reliable and efficient diagnostic methods. Conventional approaches often involve invasive procedures and can be time-consuming and costly, thereby delaying the effective treatment. The current study explores the potential of Raman spectroscopy, as a promising noninvasive technique, by analyzing human blood plasma samples from lung cancer patients and healthy controls. In a benchmark study, 16 machine learning models were evaluated by employing four strategies: the combination of dimensionality reduction with classifiers; application of feature selection prior to classification; stand-alone classifiers; and a unified predictive model. The models showed different performances due to the inherent complexity of the data, achieving accuracies from 0.77 to 0.85 and areas under the curve for receiver operating characteristics from 0.85 to 0.94. Hybrid methods incorporating dimensionality reduction and feature selection algorithms present the highest figures of merit. Nevertheless, all machine learning models deliver creditable scores and demonstrate that Raman spectroscopy represents a powerful method for future in vitro diagnostics of lung cancer.

The S-REAL study: Spanish real-world data on unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy.

OBJECTIVES: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP). METHODS: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI). RESULTS: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients. CONCLUSIONS: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.

One-year efficacy and safety of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: KYONAL study.

OBJECTIVES: Naloxegol is a peripherally acting µ-opioid receptor antagonist (PAMORA) for treatment of opioid-induced constipation (OIC). The main objective was to analyse the long-term efficacy, quality of life (QOL) and safety of naloxegol in patients with cancer in a real-world study. METHODS: This one-year prospective study included patients older than 18 years, with active oncological disease who were under treatment with opioids for pain control and Karnofsky≥50 and OIC with inadequate response to treatment with laxative (s). All the patients received treatment with naloxegol according to clinical criteria. The main efficacy objectives were measured by the patient assessment of constipation QOL questionnaire (PAC-QOL), the PAC symptoms (PAC-SYM), the response rate at day 15, and months 1-3-6-12, and global QOL (EuroQoL-5D-5L). RESULTS: A total of 126 patients (58.7% males) with a mean age of 61.5 years (95% CI 59.4 to 63.7) were included. PAC-SYM and PAC-QOL total score and all their dimensions improved from baseline (p<0.0001). At 12 months, 77.8% of the patients were responders to naloxegol treatment. Global QOL was conserved from baseline. A total of 28 adverse reactions, mainly gastrointestinal were observed in 15.1% of the patients (19/126), being 75% (21) mild, 17.9% (5) moderate and 7.1% (2) severe. Most adverse reactions (67.9%) appeared the first 15 days of treatment. CONCLUSION: The results of this first long-term and real-world-data study in patients with cancer, showed the sustained efficacy and safety of naloxegol for the treatment of OIC in this group of patients.

Efficacy of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: a 3-month follow-up analysis.

OBJECTIVES: Opioid-induced constipation (OIC) can affect up to 63% of all patients with cancer. The objectives of this study were to assess quality of life as well as efficacy and safety of naloxegol, in patients with cancer with OIC. METHODS: An observational study was made of a cohort of patients with cancer and with OIC exhibiting an inadequate response to laxatives and treated with naloxegol. The sample consisted of adult outpatients with a Karnofsky performance status score ≥50. The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) and the Patient Assessment of Constipation Symptoms (PAC-SYM) were applied for 3 months. RESULTS: A total of 126 patients (58.2% males) with a mean age of 61.3 years (range 34-89) were included. Clinically relevant improvements (>0.5 points) were recorded in the PAC-QOL and PAC-SYM questionnaires (p<0.0001) from 15 days of treatment. The number of days a week with complete spontaneous bowel movements increased significantly (p<0.0001) from 2.4 to 4.6 on day 15, 4.7 after 1 month and 5 after 3 months. Pain control significantly improved (p<0.0001) during follow-up. A total of 13.5% of the patients (17/126) presented some gastrointestinal adverse reaction, mostly of mild (62.5%) or moderate intensity (25%). CONCLUSIONS: Clinically relevant improvements in OIC-related quality of life, number of bowel movements and constipation-related symptoms were recorded as early as after 15 days of treatment with naloxegol in patients with cancer and OIC, with a good safety profile.

[Expression of proteins associated with multidrug resistance and resistance to chemotherapy in lung cancer]. / Expresión de proteínas relacionadas con resistencia a múltiples fármacos y resistencia a la quimioterapia en el cáncer de pulmón.

OBJECTIVE: Membrane transporters are proteins that play a crucial role in resistance to chemotherapy. The aim of this study was to assess the influence of membrane transporter protein expression on chemotherapeutic response. MATERIAL AND METHODS: One hundred and forty seven samples of tumor tissue were collected from 143 patients; 35 samples were obtained by bronchoscopy and 112 were surgical specimens. A total of 101 samples from 99 patients were adequate for study. Cryopreserved samples were subjected to immunohistochemical analysis to detect 3 proteins associated with multidrug resistance: P-glycoprotein (Pgp), multidrug-resistance-associated protein 1 (MRP1), and lung resistance protein (LRP). RESULTS: In 16 cases none of the proteins were expressed. A single protein was expressed in 32 (3 Pgp, 11 MRP1, and 18 LRP); 2 in 34 cases (24 Pgp and LRP; 5 MRP1 and Pgp; 5 MRP1 and LRP); and all 3 in 17 cases. No significant relationship was found between age and the expression of Pgp (P=.74), MRP1 (P=.95), or LRP (P=.26). Nor were there significant differences in number (P=.72) or type of coexpressed proteins (P=.39) by sex, by tumor stage (number, P=.55; type, P=.21), or by tumor grade (number, P=.59; type, P=.51). There was a highly significant trend toward coexpression of Pgp and LRP (P< .01) but not of Pgp and MRP1 (P=.18) or MRP1 and LRP (P=.26). MRP1 was expressed less often in adenocarcinoma. LRP was expressed less often in squamous cell carcinoma than in adenocarcinoma and undifferentiated large cell carcinoma. Coexpression of Pgp, MRP1, and LRP was observed most often in squamous cell carcinoma. CONCLUSIONS: Proteins associated with multidrug resistance are commonly expressed in lung cancer. Of the 3 proteins studied, LRP was the one most often found. Coexpression of more than 1 of the proteins was found in a considerable percentage of patients. Pgp was mainly found to be coexpressed with LRP. Pgp expression and the number of coexpressed proteins seemed to have a negative impact on response to chemotherapy.

[Expression of multiple-drug resistant proteins in lung cancer]. / Expresión de proteínas relacionadas con resistencia a múltiples fármacos en el cáncer de pulmón.

BACKGROUND: Reduction of intracellular drug accumulation plays an important role in resistance to chemotherapy in neoplasms. MDR-proteins regulate this cell activity. MATERIAL AND METHOD: A total of 147 tumor samples were collected from 143 patients. Thirty-five samples were obtained by bronchoscopy and 112 were surgical specimens. One hundred and one samples from 99 patients were valid for the study. The samples underwent cryopreservation and immunohistochemistry for detection of three multiple-drug resistant proteins (MDR-proteins): Pgp, Mrp1 and Lrp. RESULTS: No proteins were expressed in 16 patients. A single protein was expressed in 32 patients: 3 Pgp, 11 Mrp1 and 18 Lrp=0. Two proteins were expressed in 34 patients: 24 Pgp and Lrp, 5 Mrp1 and Pgp, 5 Mrp1 and Lrp=0. All three proteins were expressed in 17 patients. No differences were observed in expression according to age (Pgp [p=0.74], Mrp1 [p=0.95], Lrp [p=0.26]). No differences were found according to sex, when both the number (p=0.72) and type (p=0.39) of simultaneously expressed proteins were analyzed. No differences were observed according to tumoral stage [number (p=0.55), type (p=0.21)] or histological grade [number (p=0.59), type (p=0.51)]. The tendency toward simultaneous expression of Pgp and Lrp was highly significant (p<0.01). The same tendency was not observed in the association between Mrp1 and Lrp (p=0.26). CONCLUSIONS: MDR-proteins are frequently expressed in lung cancer. Of the three MDR-proteins studied, Lrp was the most frequent. Adenocarcinoma expressed less Mrp1 than other histological types. Squamous carcinoma expressed less Lrp than adenocarcinomas and large-cell undifferentiated carcinomas. In a considerable number of patients, more than two proteins were expressed simultaneously. Squamous-cell carcinomas tended to express Pgp, Mrp1 and Lrp simultaneously. Pgp was usually expressed in association with Lrp.