Months For Stage Research Articles

Venglustat, a Novel Glucosylceramide Synthase Inhibitor, in Patients at Risk of Rapidly Progressing ADPKD: Primary Results of a Double-Blind, Placebo-Controlled, Phase 2/3 Randomized Clinical Trial

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the formation of multiple kidney cysts that leads to growth in total kidney volume (TKV) and progression to kidney failure. Venglustat is a glucosylceramide synthase inhibitor that has been shown to inhibit cyst growth and reduce kidney failure in preclinical models of ADPKD. STAGED-PKD was a 2-stage, multicenter, double-blind, randomized, placebo-controlled phase 2/3 study in adults with ADPKD at risk of rapidly progressive disease, who were selected based on Mayo Clinic imaging classification of ADPKD class 1C, 1D, or 1E and an estimated glomerular filtration rate (eGFR) of 30-89.9mL/min/1.73m2. Enrollment included 236 and 242 patients in stages 1 and 2, respectively. In trial stage 1, the patients were randomized 1:1:1 to venglustat, 8mg; venglustat, 15mg; or placebo. In stage 2, the patients were randomized 1:1 to venglustat, 15mg (highest dose identified as safe and well tolerated in stage 1), or placebo. Primary end points were rate of change in TKV over 18 months in stage 1 and eGFR slope over 24 months in stage 2. Secondary end points were eGFR slope over 18 months (stage 1), rate of change in TKV (stage 2), and safety/tolerability, pain, and fatigue (stages 1 and 2). A prespecified interim futility analysis showed that venglustat treatment had no effect on the annualized rate of change in TKV over 18 months (stage 1) and had a faster rate of decline in eGFR slope over 24 months (stage 2). Due to this lack of efficacy, the study was terminated early. The short follow-up period after the end of treatment and limited generalizability of the findings. In patients with rapidly progressing ADPKD, treatment with venglustat at either 8mg or 15mg showed no change in the rate of change in TKV and a faster rate of eGFR decline in STAGED-PKD despite a dose-dependent decrease in plasma glucosylceramide levels. This study was funded by Sanofi. Registered at ClinicalTrials.gov with study number NCT03523728.

Resected Early-Onset Pancreatic Cancer: Practices and Outcomes in an International Dual-Center Study

BackgroundEarly-onset pancreatic cancer (EOPC), defined as age ≤ 45 years at diagnosis, accounts for 3% of all pancreatic cancer cases. Although differences in tumor biology have been suggested, available data are sparse and specific treatment recommendations are lacking. This study explores the clinicopathological features and oncologic outcomes of resected EOPC.Patients and MethodsPatients with EOPC undergoing resection between 2002 and 2018 were identified from the Heidelberg University Hospital and Johns Hopkins University registries. Median overall survival (OS) and recurrence-free survival (RFS) were analyzed, and prognostic factors were identified.ResultsThe final cohort included 164 patients, most of whom had pancreatic ductal adenocarcinoma (PDAC, n = 136; 82.9%) or IPMN-associated pancreatic cancer (n = 17; 10.4%). Twenty (12.1%) patients presented with stage 1 disease, 42 (25.6%) with stage 2, 75 (45.7%) with stage 3, and 22 (13.4%) with oligometastatic stage 4 disease. Most patients underwent upfront resection (n = 113, 68.9%), whereas 51 (31.1%) individuals received preoperative treatment. Median OS and RFS were 26.0 and 12.4 months, respectively. Stage-specific median survival was 70.6, 41.8, 23.8, and 16.9 months for stage 1, 2, 3, and 4 tumors, respectively. Factors independently associated with shorter OS and RFS were R1 resections and AJCC stages 3 and 4. Notably, AJCC 3-N2 and AJCC 3-T4 tumors had a median OS of 20 months versus 29.5 months, respectively.ConclusionDespite frequently presenting with advanced disease, oncologic outcomes in EOPC patients are satisfactory even in locally advanced cancers, justifying aggressive surgical approaches. Further research is needed to tailor current guidelines to this rare population.

Survival outcomes following treatment delays among patients with early-stage female cancers: a nationwide study

BackgroundThe coronavirus disease 2019 (COVID-19) severely hindered the timely receipt of health care for patients with cancer, especially female patients. Depression and anxiety were more pronounced in female patients than their male counterparts with cancer during treatment wait-time intervals. Herein, investigating the impact of treatment delays on the survival outcomes of female patients with early-stage cancers can enhance the rational and precise clinical decisions of physicians.MethodsWe analyzed five types of cancers in women from the Surveillance, Epidemiology, and End Results (SEER) program between Jan 2010 and Dec 2015. Univariate and multivariate Cox regression analyses were used to determine the impacts of treatment delays on the overall survival (OS) and cancer-specific survival (CSS) of the patients.ResultsA total of 241,661 females with early-stage cancer were analyzed (12,617 cases of non-small cell lung cancer (NSCLC), 166,051 cases of infiltrating breast cancer, 31,096 cases of differentiated thyroid cancer, 23,550 cases of colorectal cancer, and 8347 cases of cervical cancer). Worse OS rates were observed in patients with treatment delays ≥ 3 months in stage I NSCLC (adjustedHazard ratio (HR) = 1.11, 95% Confidence Interval (CI): 1.01–1.23, p = 0.044) and stage I infiltrating breast cancer (adjustedHR = 1.23, 95% CI 1.11–1.37, p < 0.001). When the treatment delay intervals were analyzed as continuous variables, similar results were observed in patients with stage I NSCLC (adjustedHR = 1.04, 95% CI 1.01–1.06, p = 0.010) and in those with stage I breast cancer (adjustedHR = 1.03, 95% CI 1.00–1.06, p = 0.029). However, treatment delays did not reduce the OS of patients with differentiated thyroid cancer, cervical cancer, or colorectal cancer in the early-stage. Only intermediate treatment delays impaired the CSS of patients with cervical cancer in stage I (adjustedHR = 1.31, 95% CI 1.02–1.68, p = 0.032).ConclusionAfter adjusting for confounders, the prolonged time from diagnosis to the initiation of treatment (< 6 months) showed limited negative effects on the survival of most of the patients with early-stage female cancers. Whether our findings serve as evidence supporting the treatment deferral decisions of clinicians for patients with different cancers in resource-limited situations needs further validation.

KTP 532 Laser Assisted Surgery for Oral Cavity Malignancy-A Retrospective Study.

To determine the effectiveness of KTP 532 in surgically treating early and early advanced oral malignancy with no surgical reconstruction of primary site. It is a retrospective study of 67 cases operated between 2000 to 2013 including T1, T2 and Early T3 cases, approved by ethical committee. All the cases underwent Laser assisted excision of tumour with or without Neck Dissection or Adjuvant Radiotherapy. Age of the cases varied from 20 to 80 years with mean age of 49 years. 47 cases were males and 20 were females. 26 cases in the study had neck nodes clinically whereas 41 cases had N0 status. Neck dissection was done (SOND or MRND) in 61 cases. In 6 cases (N0) no neck dissection was done. 61 cases had no loco-regional residual disease on their last follow up. Six cases had loco-regional recurrence within 6 months and salvage surgery was done. The overall mean survival was 81 months (92, 82 and 71 months in Stage I, II,III respectively). 3 year disease free survival rate was 91% as calculated using Kaplan- Meier Scale. In all these cases tumour was excised with KTP 532 laser and no reconstruction was done. Wound was allowed to heal with secondary intention. Laser assisted excision of oral malignancy is an alternative to conventional treatment with more precision, less morbidity, shorter hospital stay and better functional outcomes. The online version contains supplementary material available at 10.1007/s12070-022-03214-x.

Small Cell Carcinoma of the Vagina: First Systematic Review of Case Reports and Proposal of a Management Algorithm.

Small cell carcinoma of the vagina (SmCCV) is an extremely rare disease. Evidence-based data and specific guidelines are lacking. We conducted the first systematic review of case reports to provide the most overall picture of SmCCV. Literature search in PubMed and Scopus was performed using the terms "small cell carcinoma" and "vagina." English-language case reports of primary SmCCV up to January 2022 were included. Twenty-nine articles describing 44 cases met our inclusion criteria. We report a new case of our hospital. The global median overall survival (mOS) was 12.00 months (95% CI = 9.31-14.69). The mOS was not reached for stage I, and it was 12.00, 12.00, 9.00, and 8.00 months for stages II, III, IVA, and IVB, respectively (statistically significant differences between stage I and stages II, III, or IVA [log rank p = .003-.017]). Thirty-five cases received local treatments (77.8%). The mOS of patients treated with surgery ± complementary chemotherapy, radiotherapy ± complementary chemotherapy, chemoradiation ± complementary chemotherapy, and surgery + radiotherapy ± complementary chemotherapy were 11.00, 12.00, 17.00, and 29.00 months, respectively. The use of adjuvant or neoadjuvant chemotherapy (64.5%, mostly platinum + etoposide) showed longer mOS (77.00 vs 15.00 months). Four of 5 tested cases presented human papillomavirus infection, 3 of them presenting type 18. Small cell carcinoma of the vagina shows dismal prognosis. Multimodal local management plus complementary chemotherapy seems to achieve better outcomes. Human papillomavirus could be related to the development of SmCCV. A diagnostic-therapeutic algorithm is proposed.

Small Bowel Adenocarcinoma: 10-Year Experience in a Cancer Center-The Ottawa Hospital (TOH).

(1) Background: Small bowel adenocarcinoma (SBA) is one of the predominant primary small bowel cancers that has a dismal outcome. We aim to report 10 years of experience in SBA management at a regional cancer centre in Canada.; (2) Methods: We retrospectively analysed clinical and pathological data of patients diagnosed with an SBA between 2011 and 2021 at the Ottawa Hospital (TOH), Ottawa, Canada. We describe the clinicopathological features and outcomes, including survival. Potential prognostic factors were analysed using the Cox proportional hazard model for multivariate analysis.; (3) Results: We identified 115 patients with SBA. The duodenum was the most common SBA location representing 61% (70) of the total patients, followed by the jejunum (17%) and ileum (10%). Around 24% (27) of cases presented with bowel obstructions. The majority of patients (56%, 64) had stage IV disease on presentation. Seven patients had MSI-high tumours, while 24% (27) were MS-stable. In terms of management, 48 patients underwent curative surgical resection, 17 of whom received adjuvant chemotherapy. On the other hand, 57 patients (49.5%) with the advanced disease received palliative systemic therapy, and 18 patients (16%) had supportive care only. Over a median follow-up of 21.5 months (range 0–122), the median overall survival was 94, 61, and 34 months for stages II, III, and IV, respectively (p < 0.05). The median recurrence-free survival was 93 and 23 months for stages II and III, respectively. However, there was no statistically significant difference between TNM stages in RFS, p = 0.069. Multivariate Cox regression analysis showed only poor performance status at diagnosis as a predictor for shorter overall survival (p < 0.05). The univariate analysis didn’t show any significant correlation between RFS and covariants.; (4) Conclusions: SBA remains one of the most aggressive tumours with a dismal prognosis even after surgical resection. The optimal chemotherapy regimen has not been established. Further studies are needed to explore the role of adjuvant chemotherapy for stages I-III SBA.

Clinical Prognosis of Lung Cancer in Patients with Moderate Chronic Kidney Disease.

Simple SummaryLung cancer has a high incidence and mortality rate worldwide. In addition, lung cancer develops commonly in the elderly, and it is necessary to consider comorbidities when planning treatment. Chronic kidney disease (CKD) is a common comorbidity in patients with lung cancer. However, there are conflicting results regarding its effect on the clinical prognosis of lung cancer, and only insufficient evidence for treatment of lung cancer according to renal function. In this retrospective multicenter study, we evaluate clinical course and prognostic factors of lung cancer according to the renal function of moderate CKD patients.The clinical outcomes of patients with lung cancer coexisting with chronic kidney disease (CKD) are reported to have been conflicting. There is insufficient evidence for treatment and prognosis of lung cancer according to renal function in patients with CKD. We evaluate clinical course and prognostic factors of lung cancer according to the renal function of moderate CKD patients. A retrospective, multicenter study of lung cancer patients with moderate CKD was performed. Moderate CKD was defined as having an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. CKD was classified as stage 3, stage 4, and stage 5 according to eGFR. The cumulative mortality of lung cancer was calculated by competing risks survival analysis, and the risk factors were evaluated by the Cox-proportional hazards model. Among the lung cancer patients with moderate CKD (n = 181), median overall survival (OS) was 11.1 (4.2–31.3) months for stage 3 CKD patients, 6.0 (1.8–16.3) months for stage 4 CKD patients, and 4.7 (2.1–40.1) months for stage 5 CKD patients (p = 0.060), respectively. In a subgroup analysis, CKD stage was associated with an increased mortality in early-stage non-small cell lung cancer (NSCLC). Cox regression analysis revealed that age ≥ 75 years (adjusted hazard ratio (aHR), 1.581; 95% confidence interval (CI), 1.082–2.310), Charlson comorbidity index (aHR, 1.669; 95% CI, 10.69–2.605), and stage IV NSCLC (aHR, 2.395; 95% CI, 1.512–3.796) were associated with increased mortality risk, whereas adenocarcinoma (aHR, 0.580; 95% CI, 0.352–0.956) and stage 3 CKD (aHR, 0.598; 95% CI, 0.399–0.895) were associated with decreased mortality risk. In conclusion, the mortality risk of patients with lung cancer was lower in stage 3 CKD compared with stage 4 or 5 CKD. In addition, in the early stages of NSCLC, the CKD stage affected the prognosis, but not in the advanced stage NSCLC.

The STAGED-PKD 2-Stage Adaptive Study With a Patient Enrichment Strategy and Treatment Effect Modeling for Improved Study Design Efficiency in Patients With ADPKD

Rationale & ObjectiveVenglustat, a glucosylceramide synthase inhibitor, inhibits cyst growth and reduces kidney failure in mouse models of autosomal dominant polycystic kidney disease (ADPKD). STAGED-PKD aims to determine the safety and efficacy of venglustat and was designed using patient enrichment for progression to end-stage kidney disease and modeling from prior ADPKD trials.Study DesignSTAGED-PKD is a 2-stage, international, double-blind, randomized, placebo-controlled trial in adults with ADPKD (Mayo Class 1C-1E) and estimated glomerular filtration rate (eGFR) 45-<90 mL/min/1.73 m2 at risk of rapidly progressive disease. Enrichment for rapidly progressing patients was identified based on retrospective analysis of total kidney volume (TKV) and eGFR slope from the combined Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease and HALT Progression of Polycystic Kidney Disease A studies.Setting & ParticipantsTarget enrollment in stages 1 and 2 was 240 and 320 patients, respectively.InterventionsStage 1 randomizes patients 1:1:1 to venglustat 8 mg or 15 mg once daily or placebo. Stage 2 randomizes patients 1:1 to placebo or venglustat, with the preferred dose based on stage 1 safety data.OutcomesPrimary endpoints are TKV growth rate over 18 months in stage 1 and eGFR slope over 24 months in stage 2. Secondary endpoints include: annualized rate of change in eGFR from baseline to 18 months (stage 1); annualized rate of change in TKV based on magnetic resonance imaging from baseline to 18 months (stage 2); and safety, tolerability, pain, and fatigue (stages 1 and 2).LimitationsIf stage 1 is unsuccessful, patients enrolled in the trial may develop drug-related adverse events that can have long-lasting effects.ConclusionsModeling allows the design and powering of a 2-stage combined study to assess venglustat’s impact on TKV growth and eGFR slope. Stage 1 TKV assessment via a nested approach allows early evaluation of efficacy and increased efficiency of the trial design by reducing patient numbers and trial duration.FundingThis study was funded by Sanofi.Trial registrationSTAGED-PKD has been registered at ClinicalTrials.gov with study number NCT03523728.

Mutational landscape of pancreatic adenocarcinoma identified by prospective clinical sequencing in a nationwide cancer network.

4137 Background: Curative treatment of pancreatic adenocarcinoma (PDAC) remains a challenge. Improved understanding of the tumor biology is needed to adequately target therapies for individual patients. Tumor genomic profiling is a critical component of precision medicine for these patients to identify potential genomic alterations that can be targeted for therapy. We present a cohort of PDAC patients who underwent prospective comprehensive genomic profiling (CGP) in a national cancer network. Methods: Between 2013 and 2021, 731 patients with PDAC underwent CGP with hybrid capture of up to 406 cancer-related genes on tumor tissue for treatment decision-making. Clinically relevant genomic alterations (CRGA) were defined as associated with targeted therapies or mechanism-driven clinical trials. Patient demographics and outcomes were retrospectively reviewed with IRB approval. Results: Median patient age at presentation was 58 years (range, 26-87) and a slight majority were male (54%). Most patients presented with stage IV disease (n=457; 63%). Median overall survival (OS) was 26 months for stages I-III and 15 months for stage IV disease. A majority of patients were treated with first line chemotherapy, predominantly gemcitabine or FOLFIRINOX. Surgical resection was performed in 198 patients (27%). Genomic alterations (GA) were identified in 96% of PDAC patients. The most common GA were in KRAS (86%), TP53 (75%), CDKN2A (49%), SMAD4 (21%), ARID1A (7.8%), RNF43 (5%), BRCA2 (4%), and BRCA1 (1%). A mutation in one of the four commonly mutated genes ( KRAS, TP53, CDKN2A, or SMAD4) was identified in 92% (n=675). Common KRAS mutations were G12D(43%), G12V (30%), and G12R(16%). Median OS was significantly worse for patients with mutations in KRAS, TP53 and CDK2NA, while wild type RNF43 demonstrated improved OS (all, P&lt;0.05). 206 patients (28%) had a CRGA based on the Know Your Tumor registry trial, including mutations in BRCA1, BRCA2, BRAF, ATM, CHEK2, and ATK. Tumor Mutational Burden (TMB) was known for 345 patients and included: 292 TMB-low (85%), 49 TMB-intermediate (14%), and 4 TMB-high (1%). PD-L1 status was obtained in 33 patients, with 18 PD-L1 positive (55%). MSI status was noted for 345 patients; only 5 patients (1%) were MSI-high. Of the 39 patients with a BRCA1 or BRCA2 mutation, 30 (77%) were treated with Olaparib. Other commonly utilized therapies included Niraparib (n=56), Regorafenib (n=8), Everolimus (n=35), Erlotinib (n=8), and Cetuximab (n=7). Conclusions: In a large series of PDAC patients assayed with CGP, GA were identified in 96% but only 28% had an actionable mutation. Access to the TAPUR trial allowed for an increase in the patients identified for targeted immunotherapy between 2013 and 2019, although overall use remained low for PDAC. Further research is needed to identify therapies based on the more commonly mutated genes given their association with overall survival.

Characterization of time to diagnosis indicates shorter interval for screenable versus symptom-driven cancers.

10526 Background: Cancer screening provides a straightforward diagnostic path compared to non-screening, which often requires complex evaluation for patients with non-specific symptoms. The time to diagnosis (from clinical presentation or screening event to definitive diagnosis) captures the clinical efficiency of the journey. The study characterizes time to diagnosis for cancers with and without USPSTF Grade A/B screening recommendations. This could inform the value of screening in diagnostic management and care efficiency improvements. Methods: The Geisinger Health System Phenomics Initiative Database provides deidentified EHR and tumor registry data. Patients aged 50-74 with encounters at least biennially for six years prior to a cancer diagnosis were frequency-matched to a non-cancer control group by diagnosis year. From 18 months prior to diagnosis, equally-sized random samples were drawn (with replacement) from a time-bounded sliding window at monthly intervals. Aggregated procedure and diagnostic code counts for cancer and non-cancer samples were used to calculate the Bray-Curtis dissimilarity (BCd) statistic. The start of the diagnostic path was defined as the earliest date with a monotonically-increasing statistically-significant difference in BCd (95% CI), and was stratified into cancers with and without screening and by stage. Results: 8188 new cancer cases were identified between 2010-2019; 40% had an established screening modality (breast, lung, colorectal, cervical), 55% of which were screened prior to diagnosis. The time to diagnosis for non-screenable cancers was 6 months versus 3 months for screenable cancers. The BCd for procedures differed by 0.029 (95% CI: 0.021-0.037) between the two groups at 6 months prior to diagnosis. Stages I and IV had a time to diagnosis of 3 months across all cancers versus 7 and 6 months for stages II and III, respectively. Conclusions: We report the first known quantification of time to diagnosis across multiple cancers. Screenable cancers were associated with shorter time to diagnosis than non-screenable cancers. Stage II and III cancers took longer to diagnose than stage I and IV, likely related to early detection by screening in the former and severe symptom presentation in the latter. These novel data highlight improved time to diagnosis as another achievable benefit from expanded, multi-cancer screening.

New Staging Model for Radiation-based Hepatocellular Carcinoma Treatment: A National Multicenter Study.

The study aimed to create a new staging model for radiotherapy-based treatment for prognostic hepatocellular carcinoma (HCC) classification. The training cohort comprised 658 patients receiving stereotactic body radiotherapy and external validation cohort comprised 533 patients receiving three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. We established a modified staging system as follows: stage I, solitary nodule without macrovascular invasion, or 2-3 nodules no more than 3.0 cm apart, and performance status (PS) 0-2 (Ia: ALBI-1 grade; Ib: ALBI-2 or 3 grade); stage II: 2-3 nodules with any one nodule more than 3.0-cm apart, or ≥4 nodules, and performance status 0-2 (IIa: ALBI-1 grade; IIb: ALBI-2 grade); stage III: macrovascular invasion, regional lymph node metastasis or distant metastasis, and performance status 0-2 (IIIa: ALBI-1 grade; IIIb: ALBI-2 grade); stage IV: performance status 3-4, or performance status 0-2 with ALBI-3 grade. We analyzed long-term overall survival based on different stages. The staging model showed an excellent ability to discriminate patients according to four stages and seven substages with notably different curves in the training and validation cohort. The median survival decreased from stages I to IV with 63.0 months in stage I (not reached in Ia, and 53.0 months in Ib), 24.0 months in stage II (28.0 months in IIa, and 22.0 months in IIb), 11.0 months in stage III (18.0 months in IIIa, and 9.0 months in IIIb), and less than 9.0 months in stage IV in the training cohort. The modified staging model may provide an alternative for clinical radiation oncologists.

Treatment patterns and outcomes in early-stage ALK-rearranged non-small cell lung cancer

IntroductionWe evaluated the baseline demographics, treatment patterns, and outcomes of patients with ALK-rearranged early stage (Stage I-III) non-small cell lung cancer (NSCLC). We also evaluated the efficacy and toxicity of durvalumab consolidation treatment in patients with ALK-rearranged unresectable stage III disease. MethodsRetrospective chart-review analysis of all patients with histologically confirmed stage I-III reflexively tested ALK-rearranged NSCLC managed with curative intent at two Canadian Centers. ResultsOf 48 patients, 19 (40%) were stage I, 5 (10%) were stage II and 24 (50%) were stage-III. Median progression-free survival (PFS) was 27.6 months overall (95%CI: 20.5–51.4) and 144.4 months in stage-I, 27.6 months in stage-II and 14.9 months in stage III patients. Of 20 patients with unresectable stage-III disease treated with chemoradiation (9 also received durvalumab consolidation), 18/90% have relapsed. Median PFS was 10.9 months (95%CI:5.9–22.5). A non-significant trend toward improved PFS was seen in patients receiving additional durvalumab compared to patients treated with chemoradiation alone (median PFS, 12.5 vs 5.9 months, p = 0.16). Toxicity-related treatment modifications on subsequent first ALK-TKI at time of metastatic disease were needed in three (33%) patients who had received chemoradiation alone and two (29%) patients with consolidation durvalumab; no relevant pulmonary or hepato-toxicity was observed overall. ConclusionTreatment strategies and PFS of patients with Stage I-III ALK-rearranged NSCLC are similar to patients without molecular driver alterations. Durvalumab consolidation treatment appears generally safe in patients with unresectable stage III ALK-rearranged disease; however, the degree of benefit of such an approach remains unclear.

Demographic and Clinical Outcomes of Brazilian Patients With Stage III or IV Non-Small-Cell Lung Cancer: Real-World Evidence Study on the Basis of Deterministic Linkage Approach.

PURPOSENon–small-cell lung cancer (NSCLC) is the most common type of lung cancer and accounts for 80%-90% of the cases. In Brazil, between 2018 and 2019, lung cancer was ranked as the second most frequent cancer among men and the fourth among women. The primary objectives were to describe the journey and survival rates of patients with advanced NSCLC treated in the Brazilian private health care system (HCS).MATERIALS AND METHODSA retrospective cohort study was based on the search in administrative databases to analyze the Brazilian private HCS. Patients with advanced NSCLC diagnosed between 2011 and 2016 were included. The data on demographics, cancer-related information, treatment-related information, and resources used were collected. Survival analyses were performed using the semiparametric Kaplan-Meier method to assess mortality by NSCLC stage, with NSCLC diagnosis as the index date.RESULTSA total of 5,016 patients were included. Most patients were between 60 and 69 years old (33.6%) and had completed elementary school (52.2%). There was a greater proportion of men (58.1% v 41.9%), and the majority of patients had stage IV NSCLC (67%). It took an average of 31 days, from the first consultation, to have diagnosis. In 44% of the cases, a clinical oncologist was the first specialist in the HCS that the patient was referred to. After the diagnosis, the median time to start of treatment was 35 days. Chemotherapy alone was the most common treatment regimen (32%). The median overall survival was 11.5 months and 6 months for stage II and IV NSCLC, respectively.CONCLUSIONThis study provides contemporary data on stage III and IV NSCLC in private health care in Brazil, which has shown a high rate of metastatic disease diagnoses, high health care–related costs, and low survival rates.

Gastrointestinal Cancer Stage at Diagnosis Before and During the COVID-19 Pandemic in Japan

The COVID-19 pandemic has delayed medical consultations, possibly leading to the diagnosis of gastrointestinal cancer at advanced stages. To evaluate stage at diagnosis among patients with gastrointestinal cancer in Japan before and during the COVID-19 pandemic. This retrospective cohort study included patients in a hospital-based cancer registry who were diagnosed with gastrointestinal cancer (ie, esophageal, gastric, colorectal, pancreatic, liver, and biliary tract cancers) between January 2016 and December 2020 at 2 tertiary Japanese hospitals. The pre-COVID-19 period was defined as January 2017 to February 2020, and the COVID-19 period was defined as March 2020 to December 2020. Monthly numbers of patients with newly diagnosed cancer were aggregated, classified by stage, and compared. The study evaluated 5167 patients, including 4218 patients (2825 [67.0%] men; mean [SD] age, 71.3 [10.9] years) in the pre-COVID-19 period and 949 patients (607 [64.0%] men; mean [SD] age, 71.8 [10.7] years) in the COVID-19 period. Comparing the pre-COVID-19 period with the COVID-19 period, significant decreases were observed in the mean (SD) number of patients with newly diagnosed gastric cancer (30.63 [6.62] patients/month vs 22.40 [5.85] patients/month; -26.87% change; P < .001) and colorectal cancer (41.61 [6.81] patients/month vs 36.00 [6.72] patients/month; -13.47% change; P = .03). Significant decreases were also observed in the mean (SD) number of cases of stage I gastric cancer (21.55 [5.66] cases/month vs 13.90 [5.99] cases/month; -35.51% change; P < .001), stage 0 colorectal cancer (10.58 [3.36] cases/month vs 7.10 [4.10] cases/month; -32.89% change; P = .008), and stage I colorectal cancer (10.16 [3.14] cases/month vs 6.70 [2.91] cases/month; -34.04% change; P = .003). No significant increases were observed for esophageal, gastric, pancreatic, liver, or biliary tract cancers. A significant decrease was observed in the mean (SD) number of cases per month of stage II colorectal cancer (7.42 [3.06] cases/month vs 4.80 [1.75] cases/month; -35.32% change; P = .01); a significant increase was observed for the mean (SD) number of cases per month of stage III colorectal cancer (7.18 [2.85] cases/month vs 12.10 [2.42] cases/month; 68.42% change; P < .001). In this cohort study of patients in a hospital-based cancer registry form Japan, significantly fewer patients were diagnosed with stage I gastric and colorectal cancers during the COVID-19 pandemic. Thus, the number of screening-detected cancers might have decreased, and colorectal cancer may have been diagnosed at more advanced stages.

Clinical Features and Outcomes of Light-Chain Dominant Multiple Myeloma: A Population-Based Study

Background: There is a certain subgroup of multiple myeloma(MM) patients shows serum and urine monoclonal protein level that is negative or below thresholds considered to be measurable (Oligosecretory and non-secretory MM). In this subgroup the serum free-light-chain (FLC) assay can be used to monitor treatment response if the patient shows abnormal FLC ratio and more than 100 mg/L of involved FLC level. Yet studies about treatment outcome and clinical features in this particular patient group are still lacking. We aimed to conduct a population based study about light-chain dominant MM (LcDMM) in Korea.Methods: We performed a single-center retrospective study based on the MM patients referred to the Hematology Unit of Seoul National University Hospital from 2005 to 2015. LcDMM was defined as oligosecretory or non-secretory MM with more than 1,000 mg/dL of involved light chain. We analyzed for demographic and clinical characteristics as well as overall survival (OS) and progression free survival(PFS). Also we wanted to see whether there was a difference between characteristics of kappa and lambda LcDMM.Results: A total of 157 LcDMM cases were identified including 37 (23.5%) patients with non-secretory MM. Comparing with previously published general MM population data. LcDMM patients were younger (Median age at diagnosis = 60 years, with 66.2% of diagnosed patients being <60 years) and showed higher proportion of female (Male 51.6%). The International Staging System (ISS) distribution in stage I, II, and III was 40.4%, 19.9% and 39.7%. Among patients with available cytogenetic data, half of the patients had normal karyotype (49.0%) and the prevalence of several cytogenetic abnormalities with poor prognosis including t(4;14), del(17/17p) and t(14;16) was 1.9%, 7.0%, and 1.3% respectively.More than half of the patients were lambda-FLC involved MM (54.8%). Half of the lambda. LcDMM was ISS stage II at diagnosis (46.2%), and in contrast, half of the kappa LcDMM was Stage I (48.5%). The incidence of extramedullary organ involvement was not significantly different between kappa and lambda LcDMM. The median overall survival (OS) from diagnosis of whole LcDMM patients was 59.4 months and of each (ISS) stage was 62 months, 57 months, and 44 months in Stage I, II and III. The median OS of kappa and lambda LcDMM was 69.2 months (95% confidence interval (CI) = 38.6 to 99.7) and 40.3 months (95% CI = 16.4 to 64.1), but there was no statistically significant difference (Plogrank = 0.317)Previous exposure to thalidomide, lenalidomide, and bortezomib was 56.7% (n=89), 21.7% (n=34), and 72.3% (n=112), respectively, and 43.9% (n=69) of patients underwent hematopoietic stem cell transplantation (HSCT). Median PFS of kappa and lambda LcDMM after thalidomide treatment was 11.8 months vs 5.5 months. After lenalidomide treatment, median PFS was not reached yet. In bortezomib, lambda LcDMM showed higher median PFS than kappa LcDMM (9.0 vs 30.0). But, again, there was no statistically significant difference (Plogrank =0.214, 0.506, 0.786)Conclusion : Patients with LcDMM shows several clinical characteristics that clearly is distinguished from secretory MM. In general, the type of light chain is known to have no effect on the prognosis of MM. Yet there was a certain tendency of worse prognosis to lambda FLC involved patients in this study, and bortezomib might be considered for better response in this population. There is a limitation in statistical power of this study due to small population. But this is the largest population based study of all previously published single-center oligosecretory or non-secretory MM study and is also the first study on Asian population. DisclosuresNo relevant conflicts of interest to declare.

Maintenance visit regularity has a different impact on periodontitis-related tooth loss depending on patient staging and grading.

To assess whether maintenance variables have a differential effect on tooth loss due to periodontitis (TLP) based on staging and grading. Patients treated for periodontitis for a minimum of ≥10years follow-up were included and categorized according to their stage and grade at baseline. Impact of number, regularity, and pattern of supportive periodontal therapy visits (SPT) on TLP was explored by dividing teeth into test (5year time periods prior to TLP events) and control groups (random 5year periods without tooth loss). The regularity of maintenance visits, but not the overall quantity, had a significant impact on risk of TLP and showed higher importance as staging and grading increased (larger impact for stages III/IV and grade C). The minimum threshold of visits below which the risk of TLP was equivalent to that of the control group was one visit every 7.4months for stages I-II, 6.7months for stage III-IV, 7.2months for grade B and 6.7months for grade C. This frequency should be increased for former and current smokers, diabetics and elderly patients. Stage III and IV patients who skip more than 1year of maintenance in a 5year period have an increased risk of TLP (OR=2.55) compared to those only miss 1year. A similar trend was noted for grade C patients, but not for stages I/II or grades A/B. Lack of SPT regularity and missing multiple years of maintenance had a larger influence on risk of TLP for higher-level staging and grading.

A randomized phase 1/2 study of the safety and immunogenicity of a multivalent pneumococcal conjugate vaccine in healthy adults 50 through 85 years of age

ABSTRACT Pneumococcal disease can be serious and debilitating in older adults. Pneumococcal conjugate vaccines (PCVs), such as the 13-valent PCV (PCV13), reduce pneumococcal disease rates caused by vaccine serotypes. Development of PCVs offering additional coverage against serotypes not contained in PCV13 can reduce disease burden further. The complementary 7-valent PCV (cPCV7) contains seven non-PCV13 serotypes (8, 10A, 11A, 12F, 15B, 22F, 33F) and can expand coverage by supplementing direct or indirect protection from existing PCVs. This phase 1/2, randomized, active-controlled, observer-blinded study evaluated cPCV7 safety and immunogenicity in healthy adults 50–85 years of age. Stage 1 randomized 66 healthy adults (50–64 years) naive to pneumococcal vaccines to receive cPCV7 or licensed tetanus, diphtheria, and acellular pertussis vaccine; Stage 2 randomized 445 healthy adults (65–85 years) previously vaccinated with PCV13 to receive cPCV7 or 23-valent polysaccharide vaccine. Local reactions and systemic events up to 14 days and adverse events (AEs) through 1 month after vaccination were assessed. Immunogenicity was evaluated by serotype-specific opsonophagocytic activity (OPA) assays before and 1 month after vaccination (and after 12 months in Stage 2). Rates of local reactions, systemic events, and AEs were generally similar after receipt of cPCV7 or control. Robust OPA responses were observed for all seven serotypes 1 month after cPCV7; titers declined yet remained above baseline 12 months after vaccination. Overall, this study found that in adults ≥50 years of age, cPCV7 was safe, well tolerated, and elicited functional immune responses to vaccine serotypes. ClinicalTrials.gov: NCT03313050

Single center experience of uniportal VATS anatomical lung resections: Mid‐term oncological outcomes

BackgroundUniportal video‐assisted thoracoscopic surgery (VATS) anatomical lung resection has become widely accepted for its favorable outcomes with regard to pain. However, oncological outcomes, especially mid‐ or long‐term outcomes, are still lacking. The objective of this study was to present our eight‐year experience of uniportal VATS anatomical lung resection, including mid‐term oncological outcomes.MethodsAll consecutive patients undergoing uniportal VATS anatomical lung resection between June 2012 and February 2020 were reviewed retrospectively.ResultsWe analyzed data of 170 patients (100 male and 70 female), with a median age of 67 years. The median follow‐up time was 21 months (range 11–41). The DFS of the entire cohort was 66.3 months. Stage‐correlated DFS was 73.1 months for stage I, 42.6 months for stage II, 30.6 months for stage III and 12.5 months for stage IV. The OS of the entire court was 67 months. Stage‐correlated OS was 75.6 months for stage I, 50.2 months for stage II, 31.7 months for stage III and 12.5 months for stage IV.ConclusionsUniportal VATS anatomical lung resection for lung cancer can be performed with satisfactory mid‐term histology‐ and stage‐related outcomes, which is consistent with prior results of traditional VATS or thoracotomy.

Comparison of peer group based intervention versus family group based intervention in initial two stages of management of childhood obesity amongst school going adolescents

A Comparison of peer and family group based two stage intervention regarding management of childhood obesity is done among obese adolescents. Total 200 obese adolescents, comprising 105 males and 95 females (age 10-19 years) are studied. 100 underwent Family based counseling (Group A) and 100 to Peer based counseling (Group B). Adolescents showed improvement in health behaviors after counseling are subjected to additional 3 months of Stage 1 intervention whereas adolescents showed no improvement in health behaviors are shifted to Stage 2 intervention. At stage 1intervention, decrease in mean weight was 0.77 kg in Group A(N=100) and 0.62 kg in Group B(N=100), while decrease in mean BMI was 0.29 kg/m2 and 0.24 kg/m2 in Group A and B respectively. In Group A, only 50% adolescents showed decrease in weight and BMI, as compared to 37% in Group B at Stage I. Remaining 50% from Group A and 63% from Group B were shifted to Stage 2. At the end of 6 month stage 1, mean BMI reduction was 0.96 kg/m2 in group A and 0.75 kg/m2 in group B. Mean weight reduction was 2.58 kg in group A and 2.24 kg in group B. At stage 2, mean weight reduction was 1.46kg and 1.05kg in group A and B whereas mean BMI reduction was 0.55kg/m2 and 0.43kg/m2 in group A and B. Both Peer and family group based interventions showed good effect. Whereas family based interventions proved more beneficial in comparison to peer group interventions.

Survival of patients with asbestosis can be assessed by risk-predicting models

ObjectivesOur aim was to investigate the pulmonary function test (PFT) results of patients with asbestosis and determine whether baseline PFTs and the risk-predicting models such as gender, age and physiologic...