Advanced-stage Cancer Patients Research Articles

Efficacy of Gefitinib in Patients with Advanced Non-small-cell Carcinoma of the Lung Harboring Common, Uncommon and Complex EGFR Mutations

Background: As the commonest EGFR-TKI being used in Hong Kong, gefitinib has shown to be efficacious and safe as first-line treatment for L858R mutation and exon 19 deletions with less gastrointestinal and cutaneous adverse events than erlotinib and afatinib. The evidence for therapeutic efficacy for uncommon and complex EGFR mutations, on the other hand, is lacking. It is important to explore whether or not gefitinib is helpful for uncommon and complex EGFR mutations. Objectives: To assess the therapeutic efficacy of gefitinib, as measured by progression-free survival and overall survival, among advanced-stage lung cancer patients with common, uncommon, and complex EGFR mutations. Methods: This retrospective cohort study included 241 Chinese patients with advanced non-smallcell carcinoma of the lung harboring EGFR mutations and received gefitinib 250 mg daily as firstline treatment. The progression-free survival (PFS) and overall survival (OS) for patients with different EGFR mutations, namely exon 19 deletions, L858R mutation in exon 21, uncommon EGFR mutations, and complex EGFR mutations, were analyzed. Results: Among the 241 patients, 118 (49%) had exon 19 deletion, 104 (43%) had L858R mutation in exon 21, 6 (2.5%) had uncommon EGFR mutations, and 13 (5.4%) had complex EGFR mutations. The mean age was 69. 72% of the patients were female, and 81% were non-smokers. Patients with complex EGFR mutations, regardless of the presence of exon 19 deletion and L858R mutation as the component, have better PFS and OS than patients with single common EGFR mutations (Exon 19 deletion or L858R mutation). Patients with uncommon EGFR mutations have inferior PFS and OS than those with common EGFR mutations. Conclusion: Gefitinib is a possible option for patients with complex EGFR mutations, while it may not be the preferred treatment option in patients with single uncommon EGFR mutations.

Relationship of subjective and objective sleep measures with physical performance in advanced-stage lung cancer patients

Advanced lung cancer patients suffer from deteriorated physical function, which negatively impacts physical and psychological health. As little is known about sleep and physical function in this population, this study aimed to examine the association between subjective and objective sleep parameters and physical function among them. 164 advanced lung cancer patients were included. Objective sleep was measured by actigraphy (measured on non-dominant wrist for 72 h), and subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Performance-based physical function was measured by Timed Up and Go Test (TUGT), 6-Minute Walk Test (6MWT), Sit-to-Stand Test, and One-leg Standing Test. Univariable and multivariable regression analyses were employed to examine the association between sleep and physical function. Total sleep time (TST) was significantly associated with the 6MWT (β = 0.259; 95% CI 0.120, 0.398; P < 0.001), TUGT (β = − 0.012; 95% CI = − 0.017, − 0.008; P < 0.001) and Sit-to-Stand Test (β = 0.027; 95% CI = 0.018, 0.035; P < 0.001) after adjustment for multiple covariates. PSQI global score was only significantly associated with TUGT (β = 0.140; 95% CI = 0.000, 0.280; P = 0.050) after adjustment for multiple covariates. Shorter sleep duration significantly predicted poorer physical performance in advanced lung cancer patients, and more attention is required for those with less than 4.3 h of sleep on average.Trial registration: ClinicalTrials.gov, NCT03482323. Registered 29 March 2018, https://clinicaltrials.gov/ct2/show/NCT03482323; ClinicalTrials.gov, NCT04119778. Registered 8 October 2019, https://clinicaltrials.gov/ct2/show/NCT04119778.

The Effect Of Exercise On Chemotherapy Completion In Advanced Stage Cancers: The ENACT Trial

Exercise during chemotherapy is safe, feasible, and effective at improving physical and patient-reported outcomes and has been suggested to help improve chemotherapy completion rates. Few trials have reported these clinical outcomes and previous reports have only included one cancer site and mostly early-stage cancers. PURPOSE: To evaluate the effect of exercise on chemotherapy completion rates in advanced stage cancer patients. METHODS: The Exercise in All Chemotherapy (ENACT) trial was a single-arm pragmatic outpatient exercise trial for adults with solid tumors receiving chemotherapy. Seventy-one adults with advanced stage cancer (48F, 58.90 ± 11.20 years, 28 Stage 3) enrolled in ENACT. Patients were given home-based resistance, aerobic, flexibility, and balance exercises. Chemotherapy schedules and dosage changes for Stages 3 and 4 breast (BCa), gastrointestinal (GI), and pancreatic (PCa) cancer patients were obtained via the electronic health record. We also examined the effect of low (<70%) and high (>70%) exercise adherence on relative dose intensities (RDI) and dose delays. RESULTS: RDI differed by cancer sites: BCa (96.15%), GI (75.18%), and PCa (62.00%). BCa had a significantly higher RDI compared to GI (MD = 20.97, SE = 6.44, p = .005) and PCa (MD = 34.15, SE = 7.65, p < .001). Further, BCa patients had less weeks of dose delays (0.46 ± 1.11) compared to GI (1.24 ± 2.57), and PCa (1.19 ± 1.87). Exercise adherence had an effect on RDI and dose delays. BCa patients with low adherence had a RDI of 87.44% compared to 95.97% for high adherence. PCa patients with low adherence also had a lower RDI of 50.38% compared to 63.72% for patients with high adherence. For BCa and PCa patients, a sample size of 186 and 76, respectively, would yield 80% statistical power for detecting the observed differences. BCa patients who exercised more had no dose delays, while those who exercised less had average of 0.98 ± 1.51 weeks of dose delays. GI patients with high exercise adherence had 0.66 ± 1.51 weeks of dose delays compared to 1.68 ± 3.17 weeks for those with low exercise adherence. CONCLUSIONS: We observed that being more physically active resulted in higher RDIs and shorter time to complete chemotherapy. Although our results are not statistically significant, they show promise to the salutary effect of exercise in advanced stage patients.

Predictors of the timing of interval cytoreduction based on the number of cycles of neoadjuvant chemotherapy: a retrospective cohort

Objectives: To identify pretreatment clinical variables in ovarian cancer patients undergoing neoadjuvant chemotherapy that predict a delayed interval cytoreductive surgery. Methods: We performed an (institutional review board) IRB-approved retrospective cohort study of advanced-stage ovarian cancer patients at a single, academic, tertiary-referral center. Patients from 2008-2017 with stage III or IV disease who received NACT were included in the study. Patients without a pathologic or cytologic diagnosis, those who did not have treatment records, and those who underwent surgery at another institution were excluded. Patients who underwent interval cytoreduction (IDS) prior to their 4th cycle were compared against those who required 4 or more cycles, as our institution's practice is to undergo cytoreduction after 3 cycles if an optimal debulking is achievable. Chi-square and t-tests were used to compare clinical, radiographic, laboratory, and pathologic variables between the groups. Results: A total of 123 patients were included in the study: 70 (56.9%) patients underwent surgery at <4 cycles and 53 (43.1%) required 4 or more cycles. There was no difference in terms of age, renal function, or primary tumor size at time of diagnosis (Table 1) per number of cycles of NACT prior to IDS for either group. Patients also had a similar decrease in their Ca-125 values as measured by pre-op nadir (283.3 vs 356.6, p=0.69). Patients who underwent interval debulking surgery at <4 cycles were more likely to have a lower Charlson Comorbidity index (5.3 compared to 6.3, p=0.007) and a higher albumin (3.33 compared to 3.00, p=0.007). Not surprisingly, patients with IDS after fewer cycles received their chemotherapy in a shorter mean time period (47.2 vs 103.7 days, p<0.0001). Both groups restarted chemotherapy in a similar time frame after IDS. Conclusions: Patients with increased Charlson Comorbidity Index and a lower baseline albumin were more likely to require 4 or more cycles prior to proceeding with surgery after neoadjuvant chemotherapy for ovarian carcinoma. Ongoing assessment of these variables and other variables prior to initiating NACT may provide guidance regarding anticipated patient outcomes. To identify pretreatment clinical variables in ovarian cancer patients undergoing neoadjuvant chemotherapy that predict a delayed interval cytoreductive surgery. We performed an (institutional review board) IRB-approved retrospective cohort study of advanced-stage ovarian cancer patients at a single, academic, tertiary-referral center. Patients from 2008-2017 with stage III or IV disease who received NACT were included in the study. Patients without a pathologic or cytologic diagnosis, those who did not have treatment records, and those who underwent surgery at another institution were excluded. Patients who underwent interval cytoreduction (IDS) prior to their 4th cycle were compared against those who required 4 or more cycles, as our institution's practice is to undergo cytoreduction after 3 cycles if an optimal debulking is achievable. Chi-square and t-tests were used to compare clinical, radiographic, laboratory, and pathologic variables between the groups. A total of 123 patients were included in the study: 70 (56.9%) patients underwent surgery at <4 cycles and 53 (43.1%) required 4 or more cycles. There was no difference in terms of age, renal function, or primary tumor size at time of diagnosis (Table 1) per number of cycles of NACT prior to IDS for either group. Patients also had a similar decrease in their Ca-125 values as measured by pre-op nadir (283.3 vs 356.6, p=0.69). Patients who underwent interval debulking surgery at <4 cycles were more likely to have a lower Charlson Comorbidity index (5.3 compared to 6.3, p=0.007) and a higher albumin (3.33 compared to 3.00, p=0.007). Not surprisingly, patients with IDS after fewer cycles received their chemotherapy in a shorter mean time period (47.2 vs 103.7 days, p<0.0001). Both groups restarted chemotherapy in a similar time frame after IDS. Patients with increased Charlson Comorbidity Index and a lower baseline albumin were more likely to require 4 or more cycles prior to proceeding with surgery after neoadjuvant chemotherapy for ovarian carcinoma. Ongoing assessment of these variables and other variables prior to initiating NACT may provide guidance regarding anticipated patient outcomes.

Symptoms, Biological Stress Response, And Physical Function After Exergaming Activities Among Advanced-stage Cancer Patients

Symptoms, Biological Stress Response, And Physical Function After Exergaming Activities Among Advanced-stage Cancer Patients

Single-institution analysis of the prevalence, indications and outcomes of end-of-life radiotherapy

BackgroundRadiotherapy plays an important role for symptom control in advanced stage cancer patients. Yet patients need to be carefully selected, and its use and benefits must be weighed against time spent under treatment and patient priorities in the last phase of life. In this study, we assess prevalence, indications and outcomes of radiotherapy close to death. MethodsWe screened all radiotherapy treatments performed at the Department of Radiation Oncology of the University Hospital Zurich between January 2010 and December 2019 to identify those which occurred near patients’ end-of-life. Analyzed data was extracted from the database of the Comprehensive Cancer Center Zurich, the treatment planning system Aria® and the electronical medical records system KISIM®. ResultsWithin 60 days of death, 377 radiotherapy courses were prescribed to 280 patients, which constitutes 3.4% of all radiotherapy courses administered over the last decade at our department. Within 60–31, 30–8, and 7–0 days to death 164, 159, and 54 radiotherapy courses were prescribed, respectively. The most frequent treatment sites were brain (N = 122, 32%) and bone (N = 119, 32%), and there was no statistically significant difference in treatment site between the three sub-groups. The most common regimen was 10x3Gy (N = 130, 35%) in all three sub-groups (p = 0.23). Radiotherapy finished more than one week before death was associated with high completion rates (>80%) and treatment benefit (>55%). ConclusionPatient selection and survival prognostication remains challenging for radiation oncologists. While radiotherapy achieved high completion and success rates until one week before death, treatment within one week of death should be restricted to carefully selected patients or avoided altogether.

MO362CHECK- POINT INHIBITORS AND THEIR KIDNEY INVOLVEMENT

Abstract Background and Aims Monotherapy immunotherapy with “check-point inhibitors” (anti PD-1, Anti PD-L1) is an effective therapy to advanced-stage cancer patients. Little is known about our experience and its renal implication, although it is related to fluid and electrolyte disorders or acute kidney failure (AKI). To evaluate changes in natremia or acute renal impairment (primary endpoints) in IV stage cancer patients with lung, bladder or melanoma neoplasm who have received monotherapy with pembrolizumab (PEM), atezolizumab (ATZ) or nivolumab (NIV). At the same time, analyze if there are differences between drug administered, underlying disease or having received cisplatin previously (secondary outcomes). Method single-center retrospective analysis. Inclusion period: January 2015 to September 2020. Dose administered: PEM 2mcg/kg/21 days; ATZ 1200mg/21 days; NIV 3mg/kg/ 21 days. Changes in natremia and GFR (CDK-EPI) were evaluated in 0,1,3 months of follow-up. Patients with combined chemotherapy were excluded. Results 137 patients were included. Mean age: 64 years. Men: 71.6%. Neoplasm: lung (76.8%), bladder (7.2%), melanoma (15.9%). Patients received 27.5% PEM; 26.1% ATZ; 46.4% NIV. Between all of them, 76% had received platinum previously. Up to 13.6% developed hyponatremia and 12.40% AKI 3 months later. The decrease in GFR was significantly greater in bladder neoplasm (mean GFR 42ml / min / m2 p &amp;lt;0.01) at three months. Bladder cancer was also the most frequent (but not significant) in reduced natremia (mean Na 135mEq / L p = 0.08). There were no differences according to drug administration or having received platinum previously. 61% were death, but none of them due to a renal event. Conclusion

The SHARE study: Pilot study of a communication intervention designed to elicit advanced-stage cancer patients’ preferences and goals.

e24120 Background: Helping seriously-ill cancer patients identify and communicate their preferences for care can increase satisfaction, decrease anxiety and depression, and result in less intensive, hospital-based end-of-life medical care. We developed an intervention designed to elicit patients’ preferences and goals for care and share them with their family and care teams. We sought to pilot-test the feasibility and acceptability of this intervention in advanced cancer patients. Methods: We enrolled advanced-stage cancer patients and their clinicians at an academic and community oncology practice. Eligibility criteria included: patients with metastatic solid tumors and ≥2 prior lines of therapy or patients for whom oncologists indicated that they “would not be surprised” if the patient died within 6 months. Participants watched a 2.5 minute video which prompted them to think about how they define “a good day;” completed a 3-page brief questionnaire, which was shared with their care team; and were given a wallet card with question prompts. The primary outcomes were feasibility (i.e., ≥60% approach-to-consent ratio among eligible patients, ≥60% of participants rated the intervention positively) and acceptability (i.e., ≥60% of participants would recommend the intervention to patients like them). Secondary outcomes, measured pre- and post-intervention, included patient anxiety and distress, hope, quality of life, and therapeutic alliance with their care team. Results: Among 59 potentially eligible patients approached, 53 agreed to participate (90% approach-to-consent ratio). Four patients were non-evaluable because they died before study completion. Among the 49 remaining participants (mean age = 63 years, range 40-86 years), all completed the intervention. Overall, 45 of 49 patients (92%) rated their experience as excellent, very good, or good. Most participants agreed or strongly agreed that they would recommend the video (83%), brief questionnaire (88%), and wallet card (63%) to patients with cancers like theirs. However, only 34% of participants reported having an opportunity to review the questionnaire with their oncologist. There were no increases in patient anxiety or distress associated with the intervention or reductions in hope, quality of life, or therapeutic alliances with oncologists (all P &gt; 0.05). Conclusions: A communication intervention that combined a video, questionnaire, and wallet card was both feasible and acceptable for helping advanced cancer patients identify their care preferences and goals. Future studies should examine combining this with an intervention that primes clinicians to engage in goals of care discussions with advanced-stage cancer patients. Clinical trial information: NCT03392090.

The role of social determinants on overall survival in advanced-stage non-small cell lung cancer patients.

e21117 Background: Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer. Many studies have evaluated the association of social determinants with outcomes in early-stage NSCLC. These studies have shown statistically and clinically significant associations between overall survival (OS) and other social factors (e.g marital status, educational attainment). The aim of our study was to better understand the role of various social determinants of health (SDH) on OS in advanced-stage NSCLC patients in a community oncology practice in Florida. Methods: In this retrospective study, 125 patients with stage III and IV NSCLC were recruited between January 1st, 2014 until December 31st, 2018. We performed both categorical and continuous analyses (Pearson’s chi-square and Kruskal-Wallis test, respectively) to evaluate the association between median OS and several independent variables, including; gender, race, marital status, insurance status, living status, receiving financial assistance (FA), alcohol use, and smoking histories. OS is defined as the date of diagnosis up to the date of death. Other confounders that were analyzed included histology, treatment modality, comorbidities, and performance status of the patients. Results: Of the total study population (n = 125), 60% identified as male with a mean age of 73 years for the study population. The majority of patients (89%) identified as white; 56% were married, and 81% lived with someone. 66% of patients had an HMO insurance plan, and 51% of patients obtained FA to help with treatment care costs. 47% of patients identified as former smokers and 54% denied any alcohol use. The median OS for the patient population was 0.756 years. Chi-square analyses revealed that patients who received FA were more likely to live longer than median OS as opposed to patients that did not receive FA (OR = 2.41, 95% CI [1.18, 4.96], p = 0.050). Kruskal-Wallis analyses demonstrated that patients receiving FA had nearly a two-fold increase in median OS compared to patients without financial assistance (median OS = 1.01 years vs. 0.545 years, respectively; p = 0.013). However, other social determinants evaluated did not have a significant impact on relative OS in advanced-stage NSCLC. Conclusions: Ultimately, our study concludes that receiving FA has a significant association with increased OS in advanced-stage NSCLC patients. This study highlights the importance of reducing the financial burden of advanced-stage NSCLC patients and how FA impacts patient outcomes. Future prospective cohort studies with a larger sample size are warranted to identify other SDH, as well as the underlying mechanisms affecting median OS, in patients with advanced-stage NSCLC.

Impact of chronic obstructive pulmonary disease on immune checkpoint inhibitor efficacy in advanced lung cancer and the potential prognostic factors.

BackgroundThe coexistence of chronic obstructive pulmonary disease (COPD) in lung cancer patients often correlates with a poor clinical outcome regardless of tumor stage, mainly due to older age, poor lung function, and complex comorbid disease. Emerging data suggest that the pathogenesis of both diseases involves aberrant immune functioning. We conducted this retrospective study to describe the impact of COPD on the clinical outcomes of lung cancer patients treated with immunotherapy and investigate the potential prognostic factors.MethodsIn total, 156 patients with advanced-stage lung cancer who received at least one administration of an anti-programmed cell death 1 (PD-1)/anti-programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitor (ICI) at any treatment line at Zhongshan Hospital Fudan University between May 2018 and December 2019 were enrolled in our study. Overall survival (OS) and progression-free survival (PFS) were analyzed according to the presence of COPD. We also evaluated the prognostic value of circulating cytokine levels for clinical outcome.ResultsWe found that the presence of COPD (both spirometry-based COPD and physician-defined COPD) was significantly associated with longer PFS (316 vs. 186 days, P=0.018). Moderate and severe COPD tended to have a better impact on the survival of these patients. In the present study, we reported that patients with mixed ventilatory defects tended to have a better OS (P=0.043) and PFS (P=0.18) when treated with ICIs compared to the normal lung function group. We also found that low baseline plasma interleukin (IL)-8 and IL-2 receptor (IL-2R) levels were associated with longer PFS in patients with advanced-stage lung cancer who received ICI treatment. Furthermore, patients who had increased IL-2R levels had significantly poorer OS [hazard ratio (HR) =3.63; 95% confidence interval (CI), 0.98–13.44; P=0.040] and PFS (HR =3.241; 95% CI, 1.032–10.18; P=0.035) when treated with ICIs. Nomograms were established based on the independent prognostic factors derived from our final multivariate models.ConclusionsCOPD was associated with better survival in advanced-stage lung cancer patients treated with ICIs. Plasma IL-8 and IL-2R levels were potential prognostic factors for clinical outcome. The nomograms represent a possibly useful tool for predicting the clinical outcomes of immunotherapy.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as mortality predictor of advanced stage non-small cell lung cancer (NSCLC) with COVID-19 in Indonesia.

This study aimed to compare the mortality rate between advanced-stage non-small cell lung cancer patients (NSCLC) with and without COVID-19. This study also explores the possible laboratory characteristics used for prognostication in patients with NSCLC and COVID-19. Additionally, this study evaluated potential differences in laboratory values between the case and control groups. This is a single-center retrospective cohort study conducted in Dharmais National Cancer Hospital, Indonesia, enrolling patients with NSCLC undergoing chemotherapy or targeted therapy between May 2020 and January 2021. All patients with NSCLC and COVID-19 in these periods were enrolled into the case group. The control group was age-matched NSCLC patients without COVID-19 that was derived from the NSCLC cohort through randomization. There were 342 patients with NSCLC between May 2020 and January 2021. Twenty-seven (7.9%) of the patients were infected by COVID-19. To facilitate comparison, thirty-five age-matched controls with NSCLC were selected from the cohort. The mortality rate in patients with COVID-19 was 46.2%. Eleven patients (40.7%) had severe COVID-19, of which none survived. NLR >8.35 has a sensitivity of 83.3%, specificity of 92.9%, LR+ of 12, and LR- of 0.18. The AUC was 0.946 (95% CI 0.867-1.000), p<0.001. PLR >29.14 has a sensitivity of 75.0%, specificity of 71.4%, LR+ 2.62, LR- 0.35, and AUC 0.851 (95% CI 0.706-0.996), p=0.002. Both NLR and PLR were associated with shorter time-to-mortality in the unadjusted and adjusted model CONCLUSIONS: NLR and PLR are independent predictors of mortality in COVID-19 patients with NSCLC.

Heidelberg Milestones Communication (HeiMeKOM) - Experiences, Best Practice Examples and Recommendations from the Final Symposium on January 30 and 31 in 2020

The National Cancer Plan emphasises the importance of medical communication and calls for its integration into medical education and training. In this context, the Milestone Communication Approach meets the communicative challenges in dealing with lung cancer patients. Interprofessional tandems, consisting of doctors and nurses, conduct structured conversations at defined moments with patients and their relatives. The concept aims at shared decision making, continuity in the care of lung cancer patients and the early integration of palliative care. During the symposium on the Heidelberg Milestone Communication in January 2020, recommendations on the care situation of lung cancer patients in advanced stages were developed. In addition, the further adaptability of HeiMeKOM to other settings and hospitals and to other diseases was discussed as well as the possibility of implementing such a concept in standard care. This article presents the experiences, best practice examples and recommendations discussed during the symposium in order to enable their extrapolation to other similarly oriented projects. The long-term goal is to transfer the milestone concept to other hospital, primarily certified lung cancer centers, and to ensure permanent funding. For further dissemination of the concept and, above all, to have it established in standard care, health policy awareness and support are required in addition to the integration of the concept in competence catalogues of continuing medical and nursing education.

Computational modeling of malignant ascites reveals CCL5-SDC4 interaction in the immune microenvironment of ovarian cancer.

Fluid accumulation in the abdominal cavity is commonly found in advanced-stage ovarian cancer patients, which creates a specialized tumor microenvironment for cancer progression. Using single-cell RNA sequencing (scRNA-seq) of ascites cells from five patients with ovarian cancer, we identified seven cell types, including heterogeneous macrophages and ovarian cancer cells. We resolved a distinct polarization state of macrophages by MacSpectrum analysis and observed subtype-specific enrichment of pathways associated with their functions. The communication between immune and cancer cells was predicted through a putative ligand-receptor pair analysis using NicheNet. We found that CCL5, a chemotactic ligand, is enriched in immune cells (T cells and NK cells) and mediates ovarian cancer cell survival in the ascites, possibly through SDC4. Moreover, SDC4 expression correlated with poor overall survival in ovarian cancer patients. Our study highlights the potential role of T cells and NK cells in long-term survival patients with ovarian cancer, indicating SDC4 as a potential prognostic marker in ovarian cancer patients.

Management of the Elderly Patients with High-Grade Serous Ovarian Cancer in the REAL-WORLD Setting.

Treatment of elderly patients with neoplasia is challenging. Age is a known prognostic factor in ovarian cancer but the optimal treatment of elderly patients has not been determined. We undertook a retrospective analysis to determine clinical practice in advanced-stage ovarian cancer patients older than 70 years of age. Methods: Medical records of women with high-grade serous ovarian cancer, stage III and IV were retrospectively analyzed. Results: A total of 735 patients were identified with a median age of 61.5 years. 22.4% among them were older than 70 years of age at diagnosis. First-line Progression-Free Survival (PFS) and Overall Survival (OS) were significantly worse in elderly patients in comparison to the younger ones [mPFS 11.3 months vs. 14.8 months, (p < 0.001) and mOS 30.2 months vs. 45.6 months (p < 0.001)]. However, elderly patients were characterized by worse ECOG-Performance Status and they were more frequently treated with Neoadjuvant Chemotherapy followed by Interval Debulking Surgery, while often they were more frequently denied debulking surgery compared to patients under 70 years of age. Moreover, elderly patients received more frequently monotherapy with platinum as frontline treatment. In contrast, there was no significant difference in the outcome of the debulking surgery in comparison to the younger patients or the frequency that gBRCA test was performed. Age over 70 years did not retain its significance for either Progression-Free Survival or Overall Survival when adjusted for all other reported prognostic factors. Conclusions: Elderly ovarian cancer patients have a worse prognosis. Comprehensive geriatric assessment should be performed for the optimal treatment of these patients.

High-Dose Vitamin C in Advanced-Stage Cancer Patients.

High-dose intravenously administered vitamin C (IVC) is widely used in cancer patients by complementary and alternative medicine practitioners. The most frequent indications for IVC therapy result from the belief in its effectiveness as a potent anti-cancer agent which additionally enhances chemosensitivity of cancer cells and reduces chemotherapy-related toxicities and fatigue intensity. In this narrative review, we decided to deal with this issue, trying to answer the question whether there is any scientific evidence supporting the rationale for application of high-dose IVC therapy in advanced-stage cancer patients. Although results obtained from preclinical studies demonstrated that millimolar ascorbate plasma concentrations achievable only after IVC administration were cytotoxic to fast-growing malignant cells and inhibited tumor growth as well as prolonged the survival of laboratory animals, such positive effects were not found in human studies with advanced-stage cancer patients. We also have not found the rationale for the use of IVC to increase the effectiveness of chemotherapy and to reduce the chemotherapy-induced toxicity in the above mentioned group. Nevertheless, in palliative care, high-dose IVC might be considered as a therapy improving the quality of life and reducing cancer-related symptoms, such as fatigue and bone pain. However, because of the absence of placebo-controlled randomized trials on IVC efficacy in advanced-stage cancer patients, the placebo effect cannot be excluded.

The Impact of Programmed Death-Ligand 1 Expression on the Prognosis of Early Stage Resected Non-Small Cell Lung Cancer: A Meta-Analysis of Literatures

IntroductionPrevious studies have demonstrated that programmed cell death-ligand 1 (PD-L1) serves as biomarker for poor prognosis and survival in advanced-stage non-small cell lung cancer (NSCLC) patients. However, the merit of PD-L1 expression to predict the prognosis of early stage NSCLC patients who underwent complete resection remains controversial. In the present study, we performed a meta-analysis to investigate the relationship between PD-L1 expression and prognosis in patients with early stage resected NSCLC.MethodsElectronic databases, including PubMed, EMBASE, and the Cochrane Library, were searched until July 23 2020 for studies evaluating the expression of PD-L1 and the prognosis of resected NSCLCs. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and disease-free survival (DFS) were pooled and analyzed. Heterogeneity and publication bias analyses were also assessed.ResultsA total of 15 studies involving 3,790 patients were considered in the present meta-analysis. The pooled HR indicated that PD-L1 expression related to a much shorter DFS (HR = 1.56, 95% CI: 1.18–2.05, p < 0.01), as well a significantly worse OS (HR = 1.68, 95% CI: 1.29–2.18, p < 0.01). Furthermore, our analysis indicated that PD-L1 expression was significantly associated with gender (male vs. female: OR = 1.27, 95% CI:1.01–1.59, p = 0.038), histology (ADC vs. SCC: OR = 0.54, 95% CI:0.38–0.77, p = 0.001), TNM stage (I vs. II–III: OR = 0.45, 95% CI:0.34–0.60, p = 0.000), smoking status (Yes vs No: OR = 1.43, 95% CI:1.14–1.80, p = 0.002) and lymph node metastasis (N+ vs N−: OR = 1.97, 95% CI:1.26–3.08, p = 0.003).ConclusionsThe results of this meta-analysis suggest that PD-L1 expression predicts an unfavorable prognosis in early stage resected NSCLCs. The role of personalized anti-PD-L1/PD-1 immunotherapy in the adjuvant settings of resected NSCLC warrants further investigation.

TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 as novel biomarkers for lung cancer diagnosis and progression prediction.

Platelets contain a rich repertoire of RNA species, such as mRNAs and long non-coding RNAs. During the development of tumors, platelets are "educated" by cancer cells, altering their transcriptome and molecular content, thereby, tumor educated platelet (TEP) lncRNA profile has the potential to diagnose lung cancer. The current study was aimed to examine whether TEPs might be a potential biomarker for lung cancer. Platelet precipitation was obtained by low-speed centrifugation. TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 were selected by lncRNA microarray and validated by qPCR in a large cohort of lung cancer patients and healthy donors. Besides, we analyzed the association of their expression levels with clinicopathological features. TEP linc-GTF2H2-1 and RP3-466P17.2 were significantly downregulated, while lnc-ST8SIA4-12 was significantly upregulated in patients with lung cancer or with early-stage lung cancer as compared to healthy donors, possessing AUCs of 0.781, 0.788, 0.725 for lung cancer and 0.704, 0.771, 0.768 for early-stage lung cancer, respectively. Notably, their combination demonstrated the markedly elevated AUCs of 0.921 for lung cancer and 0.895 for early-stage lung cancer. Besides, the combination of TEP linc-GTF2H2-1 was capable to facilitate diagnostic efficiencies of CEA, Cyfra21-1, or NSE to distinguish advanced-stage lung cancer patients from early ones, with an AUC of 0.899 based on the integration of these four factors. Our data suggested that lncRNAs sequestered in TEPs enabled blood-based lung cancer diagnosis and progression prediction.

In-silico identification of subunit vaccine candidates against lung cancer-associated oncogenic viruses

Globally, ~20% of cancer malignancies are associated with virus infections. Lung cancer is the most prevalent cancer and has a 10% 5-year survival rate when diagnosed at stage IV. Cancer vaccines and oncolytic immunotherapy are promising treatment strategies for better clinical outcomes in advanced-stage cancer patients. Here, we used a reverse vaccinology approach to devise subunit vaccine candidates against lung cancer-causing oncogenic viruses. Protein components (945) from nine oncogenic virus species were systematically analyzed to identify epitope-based subunit vaccine candidates. Best vaccine candidates were identified based on their predicted ability to stimulate humoral and cell-mediated immunity and avoid self-tolerance. Using a rigorous integrative approach, we identified 125 best antigenic epitopes with predicted B-cell, T-cell, and/or MHC-binding capability and vaccine adjuvant potential. Thirty-two of these antigenic epitopes were predicted to have IL-4/IFN-gamma inducing potential and IL-10 non-inducing potential and were predicted to bind 15 MHC-type I and 49 MHC-type II alleles. All 32 epitopes were non-allergenic and 31 were non-toxic. The identified epitopes showed good conservancy and likely bind a broad class of human HLA alleles, indicating promiscuous potential. The majority of best antigenic epitopes were derived from Human papillomavirus and Epstein-Barr virus proteins. Of the 32 epitopes, 25 promiscuous epitopes were related to E1 and E6 envelope genes and were present in multiple viral strains/species, potentially providing heterologous immunity. Further validating our results, 38 antigenic epitopes were also present in the largest experimentally-validated epitope resource, Immune Epitope Database and Analysis Resource. We further narrowed the selection to 29 antigenic epitopes with the highest immunogenic/immune-boosting potential. These epitopes possess tremendous therapeutic potential as vaccines against lung cancer-causing viruses and should be validated in future experiments. All findings are available at https://webs.iiitd.edu.in/raghava/vlcvirus/.

Relationship between circulating tumor-associated autoantibodies and clinical outcomes in advanced-stage NSCLC patients receiving PD-1/−L1 directed immune checkpoint inhibition.

BackgroundDurable tumor regressions are observed in a subset of advanced-stage non-small cell lung cancer (NSCLC) patients receiving PD-1/−L1 targeted immune checkpoint inhibitors (or ‘immunotherapy’) alone or in combination with chemotherapy. However, the majority of advanced NSCLC patients receiving these agents do not experience long-term disease control. Existing methods to identify patients most likely to gain clinical benefit from PD-1/−L1 immunotherapy have limitations, creating a need for improved methods to guide treatment selection, particularly for those likely to benefit from single-agent immunotherapy. Here, we describe the development of a series of novel assays for tumor-associated autoantibodies as part of an exploratory study intended to determine if these biomarkers have potential prognostic value in this setting. MethodA selection of recombinant tumor autoantigens previously characterized for their diagnostic utility were developed and preliminarily evaluated by this study. These include: Fumarate Dehydrogenase (FH), Hydroxysteroid 17-Beta Dehydrogenase 10 (HSD17B10), Inosine Monophosphate Dehydrogenase 2 (IMPDH2), New York Esophageal Squamous Cell Carcinoma-1 (NY ESO-1), Phosphoglycerate Mutase 1 (PGAM1), and Vimentin. Custom Luminex immunobead assays were developed for these targets to quantitatively assess autoantibody levels in individual patient sera. Assays were erected as indirect immunoassays on MagPlex® Microspheres using standard carbodiimide/NHS-based chemistries, utilizing a biotin-conjugated secondary (i.e. anti-human IgG) antibody and R-phycoerythrin-conjugated streptavidin reporter system. Standard curves were created for quantitative purposes using commercially-available anti-antigen antibodies and permitted analytical performance characteristics to be calculated. These assays were used to preliminarily evaluate a series of pretreatment serum samples from stage IV NSCLC patients receiving anti PD-1/−L1 therapy after failure of at least one prior line of therapy (n = 40) and their classification efficiency calculated based on 12 months overall survival (OS) threshold. ResultsSix assays were developed that each showed dynamic ranges of four orders of magnitude and provided more than 90% classification accuracy based on the observed clinical outcome data. Inter- and intra-assay precision was assessed within these standards and overall %CVs of ≤7% and ≤ 10%, respectively, were calculated. Generally, the baseline level of autoantibodies were significantly (p < 0.05) lower in the ≥12 months survival group relative to the <12 months survival groups. Serum titers of FH, HSD170B, NY-ESO-1, and vimentin were significantly correlated with ≥12 month survival (p-value 0.0038, 0.0061, 0.0073, and 0.022, respectively). IMPDH2 and PGAM1 were found to have marginal significance (p-value 0.08 and 0.076, respectively). ConclusionThis study demonstrates an efficient and promising means for assessing circulating autoantibody titers that could be useful in selecting advanced NSCLC patients for PD-1/−L1 directed immunotherapy. Further exploration and validation of this paradigm is warranted to further refine current treatment selection methods for this therapeutic strategy.

Telemedicine as an Acceptable Model of Care in Advanced stage Cancer Patients in the Era of Coronavirus Disease 2019 - An Observational Study in a Tertiary Care Centre.

Objectives:The availability of routine care for patients with cancer during the coronavirus disease 2019 (COVID-19) pandemic has become challenging, and the use of telemedicine can be promising in this area. The objective of the study is to evaluate the feasibility of telemedicine-based palliative interventions in cancer patients.Materials and Methods:This retrospective study was conducted in a tertiary care centre with 547 follow-up patients who used palliative medicine teleconsultation services. The following data were retrieved from the records: Patient’s reason for the call, the main barriers to a hospital visit, the assistance given to them by the physician on the call and the patients’ satisfaction with the service on a 4-point scale. The data were analysed using percentages for categorical variables and mean/standard deviation for quantitative variables.Results:Out of the 547 patients, 462 (84.46%) utilised voice calling service, and the major reason for not visiting the hospital were cited to be fear of contracting COVID-19 (37.3%), inability to attend due to health constraints (7.13%) and issues with transportation (48.8%). The majority of the calls (63.62%) calls were regarding uncontrolled symptoms of the primary diseases. A total of 402 (73.49%) patients were very satisfied, and a total of 399 (72.94%) decided to continue to use this medium in the future as well.Conclusion:Telemedicine is a good modality for the assessment of chronic pain and providing symptomatic supportive care in patients with cancer in the COIVD-19 pandemic.