IIIA Patients Research Articles

Perceptions of Controversies and Unresolved Issues in the 2014 FIGO Staging System for Endometrial Cancer: Survey Results From Members of the International Society of Gynecological Pathologists and International Gynecologic Cancer Society.

Long-standing controversial and unresolved issues in the current "International Federation of Gynecology and Obstetrics" staging system for endometrial cancer are well-recognized by pathologists and clinicians alike and exist primarily as a result of limitations to the existing literature. To guide the design of future outcome-based studies specifically aimed at resolving such gaps, the International Society of Gynecologic Pathologists developed a survey of the current perceptions of pathologists (n = 172) and clinicians (n= 135) from the International Society of Gynecological Pathologists and from the International Gynecologic Cancer Society on areas for potential refinement of the current International Federation of Gynecology and Obstetrics staging system. The highest priority issues for pathologists and clinicians alike were the need to determine whether stage IIIA patients (ovarian/fallopian tube involvement) can be reliably separated into favorable versus unfavorable outcome groups to avoid over-treatment of the former group and to determine whether stage IIIC patients (lymph node metastases) can be separated into favorable versus unfavorable outcome groups based on the size of lymph node metastases. The majority of pathologists and clinicians viewed lymphovascular space invasion as an independent prognostic variable and favored incorporating lymphovascular space invasion into staging, though the level of support did not meet the threshold of 75% in support that we used to define a formal consensus. While pathologists did agree on the prognostic value of reporting the extent of lymphovascular space invasion, there was no consensus on the diagnostic criteria to distinguish focal versus substantial involvement. The majority of pathologists and clinicians viewed that a universally accepted protocol for sentinel lymph node ultra-staging is lacking. Both survey groups conveyed a slight preference for incorporating tumor histotype and molecular classification into staging but the support was short of the 75% threshold for formal consensus. Collectively, this survey permits the International Society of Gynecological Pathologists to develop a pathologist and clinician-driven long-term strategy for prioritizing and designing outcome-based studies specifically targeted to resolving controversial and unresolved issues in the International Federation of Gynecology and Obstetrics staging of endometrial cancer.

Enrolling patients in Cardiac Amyloid Reaching for Extended Survival (CARES) trials: Two placebo-controlled, double-blind, randomized, international phase 3 trials assessing CAEL-101 in patients with Mayo stage IIIa or stage IIIb AL amyloidosis.

TPS8071 Background: Light-chain (AL) amyloidosis is a rare, progressive, systemic disorder caused by plasma cell dyscrasia (PCD). Amyloid fibrils deposit in organs leading to progressive organ damage and death. Prognosis is poor for patients with cardiac involvement. Median survival is 24 and 4 months for patients in Mayo Stages IIIa and IIIb (based on the 2013 European Modification of the Mayo 2004 staging criteria), respectively. The standard of care (SoC) is anti-PCD therapy to suppress amyloid fibril generation. As yet, there are no therapies that remove deposited fibrils. CAEL-101 is a monoclonal antibody that binds to amyloid fibrils and may facilitate their systemic removal, improve organ function, and patient survival. These ongoing trials will evaluate the efficacy and safety of CAEL-101 as first-in-class treatment to reduce amyloid burden in patients with cardiac AL amyloidosis. Notably, 301 (Mayo Stage IIIb) is the first randomized, placebo-controlled efficacy clinical trial to formally assess the effects of a pharmacological in this severely ill population. Because the median expected survival for Mayo Stage IIIb patients is far shorter than for Mayo Stage IIIa patients, the resulting sample size required for the Mayo Stage IIIb study is less than for the Mayo Stage IIIa study. The objective of these trials is to evaluate the efficacy and safety of CAEL-101 when administered concurrently with SoC anti-PCD therapy in treatment-naïve patients with cardiac AL amyloidosis in Mayo Stages IIIb (NCT04504825; 301) or IIIa (NCT04512235; 302). Methods: These international, multicenter, double-blind, randomized, phase 3 trials, initiated in 2020, are enrolling patients at > 100 sites in > 20 countries. Newly diagnosed adults with AL amyloidosis stage IIIb or IIIa measurable hematologic disease, and histopathological diagnosis of amyloidosis with cardiac involvement are eligible. Patients with other forms of amyloidosis, symptomatic orthostatic hypotension, or supine systolic blood pressure < 90 mm Hg are ineligible. Patients in Mayo Stages IIIb (N = 124) and IIIa (N = 267) are being randomized 2:1 to receive once-weekly IV infusions of CAEL-101 (1000 mg/m2) or placebo for 4 weeks, followed by maintenance dosing every 2 weeks. In these event-driven studies, treatment will continue to a minimum of 101 and 79 events for 301 and 302, respectively. Patients will receive concurrent institutional SoC anti-PCD therapy at the discretion of the investigator. Overall survival (primary endpoint) will be analyzed via time-to-event log-rank statistics. Secondary endpoints include functional outcomes, quality of life, and echocardiography. Clinical trial information: NCT04504825 , NCT04512235 .

International Center-Level Variation in Utilization of Completion Lymph Node Dissection and Adjuvant Systemic Therapy for Sentinel Lymph Node-Positive Melanoma at Major Referral Centers.

The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma. Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization. We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics. Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients. There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.

The accuracy of clinical staging of stage I-IIIA non-small cell lung cancer by using thoracic computed tomography

Purpose: To assess the accuracy of clinical staging of stage I-IIIA non-small cell lung cancer (NSCLC) by using thoracic computed tomography (CT). Patients and Methods: Medical records of patients with NSCLC operated in two years 2018-2019 at Surgery Department No 2, HCMC Oncology Hospital were studied retrospectively. Results: Thoracic CT diagnosed tumor stage with an accuracy of 79% but failed to detect T3-4 disease in 8% of cases. Of nodal disease, thoracic CT had a diagnostic accuracy of 58% but misclassified N2 disease in 18% of cases. Agreement was poor between clinical and pathologic stage (Kappa coefficient= 0.186). Only 48% of patients was diagnosed accurately, and clinically understaged patients (45%) were more frequent than clinically overstaged one. Thoracic CT had a low sensitivity of only 19% in detecting stage IIIA disease, with 13 stage IIIA patients (21%) were missed diagnosis. Conclusion: Thoracic CT is not an ideal means for clinical staging of stage I-IIIA non-small cell lung cancer. To prevent the worsened outcomes associated with inaccurate staging, physicians should rely on established staging guidelines. Key words: non-small cell lung cancer, clinical staging, thoracic computed tomography

Does Stage Migration Occur as a Consequence of Omitting Completion Lymph Node Dissection for Melanoma?

Completion lymph node dissection (CLND) is no longer recommended routinely in the treatment of melanoma. CLND omission may understage patients for whom the distinction between stage IIIA and IIIB-C could alter adjuvant therapy recommendations. The aim of this study is to determine if stage migration has occurred with the declining use of CLND. Patients with clinically node-negative ≥T1b cutaneous melanoma were identified from the National Cancer Database (NCDB) from 2012 to 2018. CLND utilization and changes in AJCC staging were analyzed. Patients undergoing sentinel lymph node biopsy (SLNB) alone were compared with those undergoing SLNB + CLND. Overall, 68,933 patients met inclusion criteria and 60,536 underwent SLNB, of which 9031 (14.9%) were tumor positive. CLND was performed in 3776 (41.8%). Patients undergoing CLND were younger (58 versus 62 years, p < 0.0001) and more likely male (61.5% versus 57.9%, p = 0.0005). Patients were more likely to have an N classification >N1a if they received SLNB + CLND (36.8%) versus SLNB alone (19.3%), p < 0.0001. This translated to a small difference in stage IIIA patients between groups (SLNB alone 34.0%, SLNB + CLND 31.8%, p < 0.0001). Of the patients with T1b/T2a tumors who would be upstaged from IIIA to IIIC with identification of additional positive nodes, IIIC incidence was only slightly higher after SLNB + CLND compared with SLNB alone (4.4% versus 1.1%, p < 0.0001). CLND utilization dramatically decreased from 59% in 2012 to 12.6% in 2018, p < 0.0001. However, the incidence of stage IIIA disease for all patients remained stable over the 7-year study period. While the utilization of CLND after positive SLNB has declined dramatically in the last 7 years, stage migration that may affect adjuvant therapy decisions has not occurred to a clinically meaningful degree.

Adjuvant chemoradiotherapy in resected gallbladder cancer: A SEER-based study

BackgroundThe prognosis of gallbladder cancer (GBC) is dismal. This study aimed to compare the outcomes of adjuvant chemoradiotherapy (ACR) with those of surgery alone (S) and adjuvant chemotherapy (AC). MethodThe Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify patients diagnosed with GBC and undergoing surgery between 2004 and 2015. The patients were divided into the S, AC, and ACR groups according to their treatment. Categorical variables were compared by Pearson’s chi-square test, and a 1:1:1 propensity score matching analysis (PSM) was performed. Overall survival was assessed by Kaplan-Meier curves with log-rank tests. Subgroup analyses were conducted. ResultA total of 5451 patients were identified in the SEER database. After PSM, the two-year survival among patients who received S, AC, and ACR was 36%, 39%, and 45%, respectively. ACR was associated with improved two-year survival (p < 0.001), while the survival rates were similar in the AC and S groups (p = 0.127) but better in the ACR group than in the AC group (p = 0.012). Subgroup analyses indicated that while the two-year survival rates did not differ significantly in stage II GBC patients between the groups (all p > 0.05), ACR was associated with significantly improved two-year survival in stage Ⅲa (p = 0.008), Ⅲb (p < 0.001), and Ⅳb (p < 0.001) GBC patients. ConclusionThe combination of surgery and ACR as the treatment modality provided greater survival benefits for GBC patients, particularly for those with advanced tumor staging.

Association of HPV Genotyping with HIF1-Alpha in Advanced Cervical Cancer on Response to Radiotherapy

AIM: This study aims to determine the relationship between the HPV genotype in uterine cervical cancer and the expression of HIF-1α due to tissue hypoxia and its impact on radiation response. METHODS: This study is an analytic and observational study with a cross-sectional design with the inclusion criteria in this study that was new cervical cancer Stage IIB, IIIA, IIIB, and IVA patients treated at the oncology polyclinic who had never undergone radiotherapy and would be treated with radiation. RESULTS: Sixty patients advanced cervical cancer aged 25 to &gt;45 years were involved patients. The majority had HPV genotype 16 infections. There was no significant relationship between treatment response and HPV genotype (HPV 16 genotype [p = 0.844], HPV 18 genotype [p = 0.161], other HPV genotypes [p = 0.108]), radiation response with HIF-1α expression (p = 0.503; OR 1.569 [0.417–5.899]), HIF1α expression with HPV genotype (HPV genotype 16 (p = 0.648; OR 1,357 [0.356–5.041]), HPV 18 genotype (p = 0.344; OR 1,458 [0.089–2.373]), and other HPV genotypes (p = 0.505; OR 1.667 [0.368–7.553]) as well as HIF-1α expression and HPV genotypes to radiation response (p &gt; 0.05). CONCLUSION: Cervical cancer with infection with HPV Genotype 18 tends to express HIF1α strongly and increased partial radiation response. Overall statistically, there was no significant association between infection with certain genotypes of HPV with radiation response or HIF-1α expression in tumor tissue with radiation response.

Treatment patterns and long-term survival outcomes for patients with stage III non-small cell lung cancer: A retrospective study.

Lung cancer is the leading cause of cancer-related deaths in Australia with poor long-term survival outcomes. Stage III non-small cell lung cancer (NSCLC) is a highly heterogenous group with diverse tumor characteristics and multiple, possible treatment options. We present retrospective data on patient characteristics, treatment patterns, and long-term outcomes in stage III NSCLC patients treated at a single cancer center in New South Wales, Australia. Stage III NSCLC patients were identified from the 'Nepean Cancer Research Biobank'. Patient demographics, cancer-related information, and long-term follow-up data were collected and analyzed. A total of 88 patients were eligible for analysis with 61% of them diagnosed as stage IIIA, 35% IIIB, and 4% IIIC. Induction chemotherapy was administered in 20% of the patients. Overall, 48% of the study population underwent surgery, and 38% underwent concurrent chemoradiotherapy (CCRT). Both median progression-free survival and overall survival (OS) were superior in stage IIIA patients in comparison to stage IIIB (and IIIC) patients (22 vs. 11 months, p=.018; and 58 vs. 19 months, p=.048, respectively). Patients who were younger (<65 years old), good Eastern Cooperative Oncology Group performance status (ECOG PS <2), and females had better prognosis on univariate analysis. There was a nonstatistically significant trend toward better median OS with CCRT in comparison to surgery (58 vs. 37 months, p=.87). Long-term outcomes remain poor, and hence better treatment strategies are urgently needed in stage III NSCLC. Equally, more robust, prospective studies would help delineate the optimal treatment modality in these patients.

Long-term outcomes of stage IIB–IV melanoma patients: nationwide data from Norway

Aim: This study was performed to investigate the characteristics and overall survival (OS) of patients with completely resected stage IIB-IV cutaneous melanoma identified in the Cancer Registry of Norway. Methods: A retrospective cohort study of all adult patients with stage ≥IIB cutaneous melanoma was performedin Norway (January 2008 to December 2018), excluding patients with stage IV melanoma without evidence of surgery. Results: 5-year OS varied by stage (IIB 65%, IIC 38%, IIIA 79%, IIIB 66%, IIIC 52%, IIID 37%and IV 39%). Adjusted Cox models showed that stage IIIA and IIIB patients showed similar survival to stage IIB patients (hazard ratio [95% CI]: IIIA 0.67 [0.44-1.04]; IIIB 1.18 [0.96-1.45]), while all other stages had lower survival than IIB. Conclusion: Survival for stage II patients, particularly IIC, can be poor and in some cases worse than patients with more advanced stage melanoma. Our data highlight an unmet need for effective adjuvant treatment options amongstage IIB/C patients.

Characteristics of Indian stage IIIA and IIIB operable lung cancer patients. Do T-ratio and young age predict long-term outcomes?

Introduction: Young lung cancer patients are considered to be aggressive and inferior survival outcomes. However, the behavior of locally advanced (Stage IIIA-IIIB) young Indian lung cancer patients undergoing surgery has not been adequately evaluated.

Real-world adjuvant chemotherapy patterns and outcomes among elderly patients with resected early non-small-cell lung cancer in the USA.

Background: This study investigated real-world treatment patterns and overall survival (OS) in early non-small-cell lung cancer patients and the association between OS and time to adjuvant treatment. Materials & methods: This retrospective study using Surveillance, Epidemiology, and End Results data linked with Medicare claims included resected early non-small-cell lung cancer patients between 2010 and 2015. Unadjusted OS analyses used Kaplan-Meier curves; adjusted OS analyses used extended Cox proportional hazards models. Results: Only 54-71% of stage II-IIIA patients received any adjuvant treatment. Adjusted risk of death was higher when starting treatment outside 6-8weeks after surgery (p<0.05). Conclusion: Improved systemic therapy in the adjuvant chemotherapy setting is needed.

The impact of omentectomy on cause-specific survival of Stage I-IIIA epithelial ovarian cancer: A PSM-IPTW analysis based on the SEER database.

Routine omentectomy is generally performed during surgery for patients with epithelial ovarian cancer (EOC). The current study aims to evaluate the impact of omentectomy on cause-specific survival of Stage I-IIIA EOC patients. Patients who presented with clinical Stage I-IIIA serous, clear cell, endometrioid, and mucinous ovarian cancers were selected from the SEER Database for the period between 2004 and 2018. We extracted clinicopathological data and surgical information with the focus on the performance of omentectomy and lymphadenectomy. Binary logistic regression and recursive partitioning analyses were conducted to identify the significant factors for the performance of omentectomy during surgery. Propensity score matching (PSM) and inverse probability treatment weighting (IPTW) techniques were utilized to balance confounding factors. Multivariate, exploratory subgroup analyses and sensitivity analyses were conducted to evaluate the impact of omentectomy on cause-specific survival (CSS). A total of 13,302 patients with EOC were enrolled in the study. The cohort comprised 3,569 endometrioid, 4,915 serous, 2,407 clear cell, and 2,411 mucinous subtypes. A total of 48.62% (6,467/13,302) of patients underwent the procedure of omentectomy during primary surgery, and only 3% absolute improvement in CSS at the individual level was observed, without statistical significance based on multivariate analysis. According to the regression-tree model with recursive partitioning analysis, the procedure of lymphadenectomy was found to be the strongest factor to distinguish the performance of omentectomy, followed by the tumor stage. Patients who underwent omentectomy were more likely to be managed in Stage I than those who underwent lymphadenectomy. After PSM-IPTW adjustment, the inclusion of omentectomy in the initial surgical procedure did not demonstrate a beneficial impact on CSS compared with those who did not undergo the procedure. Exploratory subgroup analysis indicated that the performance of omentectomy improved 5-year CSS in Stage II-IIIA patients. In the sensitive analyses for various tumor stages, omentectomy appeared to benefit only Stage II patients. However, patients across various stages seemed to benefit from the performance of lymphadenectomy, irrespective of the performance of omentectomy on them. Routine omentectomy may not be associated with survival benefit for patients with a grossly normal-appearing omentum, especially for those with clinical Stage I epithelial ovarian cancers.

Association of travel distance, surgical volume, and receipt of adjuvant chemotherapy with survival among patients with resectable lung cancer

ObjectiveRegionalization of surgery for non–small cell lung cancer (NSCLC) to high-volume centers (HVCs) improves perioperative outcomes but frequently increases patient travel distance. Travel might decrease rates of adjuvant chemotherapy (AC) use, however, the relationship of distance, volume, and receipt of AC with outcomes is unknown. Our objective was to evaluate the association of distance, volume, and receipt of AC with overall survival among patients with NSCLC. MethodsPatients with stage I to IIIA (N0-N1) NSCLC were identified between 2004 and 2018 using the National Cancer Database. Distance to surgical facility was categorized into quartiles (<5.1, 5.1 to <11.5, 11.5 to <28.1, and ≥28.1 miles), and HVCs were defined as those that perform ≥40 annual resections. Patient characteristics and likelihood of receiving AC anywhere were determined. Propensity score-matched survival analysis was performed using Cox models and Kaplan–Meier curves. ResultsOf the 131,982 patients included, 35,658 (27.0%) were stage II to IIIA. Of the stage II to IIIA cohort, 49.6% received AC, 13.1% traveled <5.1 miles to low-volume centers (LVCs), and 18.1% traveled ≥28.1 miles to HVCs (P < .001). Among stage II to IIIA patients who traveled ≥28.1 miles to HVCs, 45% received AC versus 51.5% who traveled <5.1 miles to LVCs (incidence rate ratio, 0.88; 95% CI, 0.83-0.94; <5.1 miles to LVC reference). Patients with stage II to IIIA NSCLC who traveled ≥28.1 miles to HVCs and did not receive AC had higher mortality rates than those who traveled <5.1 miles to LVCs and received AC (median overall survival, 52.3 vs 36.7 months; adjusted hazard ratio, 1.41; 95% CI, 1.26-1.57). ConclusionsIncreasing travel distance to surgical treatment is associated with decreased likelihood of receiving AC for patients with stage II to IIIA (N0-N1) NSCLC.

Chemotherapy exacerbates the survival paradox of colon cancer: a propensity score matching analysis.

Colon cancer is one of the most common tumor diseases in the world. Currently, clinicians usually evaluate the survival and prognosis of patients according to their tumor-node-metastasis (TNM) stage. However, current studies have found that there is a certain survival paradox in TNM staging. In the Surveillance, Epidemiology, and End Results (SEER) database, patients diagnosed with colon cancer by surgical pathology from 2004 to 2011 were selected for analysis of 5-year overall survival (OS). Propensity score matching (PSM) was performed to analyze the difference in survival between different stages and the effect of chemotherapy on prognosis. The OS of stage IIIA colon cancer sufferers was significantly superior to stage IIB/IIC and separate stage IIB or IIC colon cancer patients before and after PSM analysis (P<0.05 for all). Moreover, the difference in survival was more significant when stage IIB/IIC patients were compared with stage IIIA patients with chemotherapy. The survival paradox existed both in all stage IIB/IIC patients, or individual stage IIB or IIC patients compared with stage IIIA sufferers, and the survival paradox between stage IIIA and stage IIC was more obvious. Moreover, chemotherapy had a positive effect on the prognosis of patients with stage IIIA, IIC and IIB in this study. Chemotherapy exacerbates the survival paradox of colon cancer, even if it is not the cause of the survival paradox.

Neoadjuvant nivolumab with chemotherapy: A miraculous new regime in treatment of resectable lung cancers.

Madam, lung cancer is one of the commonly diagnosed causes of cancer mortality and morbidity worldwide, accounting for approximately 1.76 million deaths annually.1 In the past overall survival in patients with non-small cell lung cancer (NSCLC) remained uncertain. Many treatment regimens were under trial2 until, a breakthrough study incorporating neoadjuvant nivolumab with chemotherapy showed tremendous success in phase 3 CheckMate 816 trail3. Moreover, the FDA has recently approved this therapy for early-stage NSCLC.4 Nivolumab is an anti–programmed death 1 (PD-1) human antibody, which restores antitumor T cells activity. Whereas platinum-doublet chemotherapy improves antitumor immunity.3 In this trail, approximately 350 patients were randomly assigned in an equal ratio to receive nivolumab (360 mg) plus chemotherapy or chemotherapy alone for consecutive 3 weeks for three cycles before surgery. Two primary end points were established, event-free survival and complete pathological response. Median event-free survival was 31.6 months with nivolumab plus chemotherapy compared to 20.8 months with chemotherapy alone (hazard ratio for disease progression, recurrence, or death, 0.63; P=0.005). The pathological complete response was 24.0% in the nivolumab plus chemotherapy group and 2.2% in chemotherapy alone group (odds ratio, 13.94; P&lt;0.001). Also, no surgery-related adverse events were observed with the addition of nivolumab to neoadjuvant chemotherapy.3 It concludes that nivolumab with chemotherapy showed promising results than chemotherapy alone in patients with resectable NSCLC. However, stage IIIA patients were majorly benefited than stage IB or II patients.3 Therefore, it is imperative that more clinical trials must be conducted to obtain maximum benefit at all possible stages and a proper follow up for data is needed to draw better conclusions.

Outcomes by Cardiac Stage in Patients With Newly Diagnosed AL Amyloidosis: Phase 3 ANDROMEDA Trial

BackgroundPatients with amyloid light chain amyloidosis and severe cardiac dysfunction have a poor prognosis. Treatment options that induce rapid and deep hematologic and organ responses, irrespective of cardiac involvement, are needed. ObjectivesThe aim of this study was to evaluate the impact of baseline cardiac stage on efficacy and safety outcomes in the phase 3 ANDROMEDA trial. MethodsRates of overall complete hematologic response and cardiac and renal response at 6 months and median major organ deterioration–progression-free survival and major organ deterioration–event-free survival were compared across cardiac stages (I, II, or IIIA) and treatments (daratumumab, bortezomib, cyclophosphamide, and dexamethasone [D-VCd] or bortezomib, cyclophosphamide, and dexamethasone [VCd]). Rates of adverse events (AEs) were summarized for patients with and without baseline cardiac involvement and by cardiac stage. ResultsMedian follow-up duration was 15.7 months. The proportions of stage I, II, and IIIA patients were 23.2%, 40.2%, and 36.6%. Across cardiac stages, hematologic and organ response rates were higher and major organ deterioration–progression-free survival and major organ deterioration–event-free survival were longer with D-VCd than VCd. AE rates were similar between treatments and by cardiac stage; serious AE rates were higher in patients with cardiac involvement and increased with increasing cardiac stage. The incidence of cardiac events was numerically greater with D-VCd vs VCd, but the rate of grade 3 or 4 events was similar. The exposure-adjusted incidence rate for cardiac events was lower with D-VCd than VCd (median exposure 13.4 and 5.3 months, respectively). ConclusionsThese findings demonstrate the efficacy of D-VCd over VCd in patients with newly diagnosed amyloid light chain amyloidosis across cardiac stages, thus supporting its use in patients with cardiac involvement. (NCT03201965)

307P Differential expression profiling of transcripts in stage IIIA non-small cell lung cancer (NSCLC) of smokers and non-smokers cases of north India: A geneto-environmental study

Several epidemiological and experimental studies suggest that the etiology of many chronic illnesses is caused by the joint effect between genetics and the environment. Smoking tobacco is the major hazard feature for lung cancer in Indian subcontinent especially men, compare to woman where, other important risk factors i.e., exposure to agents and level of pollutions are responsible. So, the aim of the study is to compare the expression level of transcript-based biomarkers IDH1, CEA, Cyfra21-1, and TPA in NSCLC fifty tumor tissue stage IIIa patients compared to control benign tissues of smokers and non-smokers cases living in areas with air quality categorized as poor (AQI 201–300) or moderate (AQI 101–200).

The Validation of Predictive Risk Scoring Model of Radiation Pneumonitis (RP) in Lung Cancer Patients

<h3>Purpose/Objective(s)</h3> In our previous research, pulmonary emphysema (PE) was reported as a risk factor of radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC). Subclinical interstitial lung disease (SILD) was associated with severe RP in small cell lung cancer patients. A predictive risk scoring model of RP was developed in stage IIIA or Stage IIIB NSCLC patients receiving radical radiotherapy. The risk score has not been validated using an independent dataset. The aim of this study was to validate the predictive risk score which established in our previous study and evaluate the predictive value of the model. <h3>Materials/Methods</h3> From January 2019 to October 2021,129 lung cancer patients were recruited in study which included in validation group. Those patients were received thoracic radiotherapy with ≥50Gy total radiotherapy dose. The risk scoring model in our previous research as follow: PRS=5 (if subclinical ILD grade≥1) + 3 (if age >68 years) + 3 (if PE grade >1). According to the risk score, the cases in validation group were scored, predictive value of this model were evaluated by receiver operator characteristic curve (ROC) using statistical software. The decision curve analysis was constructed using Stata 17.0 software. <h3>Results</h3> In 129 eligible patients, 13(10.08%, 13/129) developed grade 1 RP, 15(11.62%, 15/129) developed grade 2 RP, grade 3 and grade 4 RP were not observed. 23 (16.60%, 23/129) had PE grade >1. Risk scores of all patients were calculated according to the risk score, 37 had 3 points which incidence of RP ≥2 grade was 13.50%, 2 had 5 points which incidence of RP ≥2 grade was 100.0%, 3 had 6 points which incidence of RP ≥2 grade was 33.33%. ROC curve was plotted according to the risk score of all patients, the area of ROC curve (AUC) was 0.695 (95%CI: 0.541-0.849, P < 0.05). The decision curve indicated that the net benefit of the model was higher in the high-risk threshold of 0.2-0.3. <h3>Conclusion</h3> The previous predictive risk scoring model indicated good discrimination and clinical application value, which can be used in clinical treatment.

Implementation of Melanoma Guidelines in the Multidisciplinary Setting: A Qualitative Analysis

INTRODUCTION: Treatment of advanced melanoma has evolved dramatically recently. Randomized trials now support omitting completion lymph node dissection (CLND) and offering adjuvant systemic therapy for many patients with sentinel lymph node–positive melanoma. Recent data from an international melanoma consortium suggest wide variation in CLND and adjuvant therapy utilization. We aimed to explore how providers consider multidisciplinary treatment options in this setting. METHODS: We conducted semi-structured interviews among surgical oncologists, medical oncologists, and otolaryngologists. Two researchers performed analysis through independent data abstraction of transcripts. Findings were discussed to reach consensus. RESULTS: All participants (n = 17) practiced at a cancer center in an academic setting. Melanoma comprised an estimated 30% to 80% of their practice (only 2% to 15% for otolaryngologists). Participants described melanoma care as inherently “multidisciplinary.” Many noted the importance of real-time conversations among providers, particularly those facilitated by shared clinic days or space, for everyday decision-making compared with formal tumor boards. Despite stating a belief that their practice mirrored other providers within and outside their institutions, participants revealed differing perspectives on CLND and adjuvant therapy (Table). Multidisciplinary care presented challenges for melanoma surveillance because surgical oncologists expressed desire to retain ownership of patients undergoing active surveillance but did not feel comfortable overseeing needs related to adjuvant therapy. Both surgical and medical oncologists noted potential redundancy in roles and burden to patients in the form of uncoordinated visits and scans. Table. - Differences in Perspectives on Completion Lymph Node Dissection (CLND) and Adjuvant Systemic Therapy Treatment option Representative example (surgical oncology) Representative example (medical oncology) Representative example (otolaryngology) Completion lymph node dissection At our institution almost never do patients get a [CLND]. Soon after the trials, there was some ambiguity about should some patients that may not have been as well represented in those trials be considered for completion, and there’s probably less issue there. Probably the main factor that pushes for dissection now would be ability to comply with routine surveillance. (Participant 7) I have seen somewhat of a push for surgery just because all of our adjuvant trials were done in patients who did have a nodal basin dissected. So it’s a little bit of a different population that we’re actually treating than was studied in [MSLT-II] because we may have patients who have residual disease. So to be more purely like the trial, there are sometimes people who push for a lymph node dissection. (Participant 1) Some of this really just relates to your philosophy of approaching cancer and surgical aggressiveness in general. I generally err on the side of being a more conservative surgeon, which applies not just to melanoma. So I am a bit more reticent to recommend a completion than some of my colleagues, but that’s not to say they’re wrong and I’m right. (Participant 14) Adjuvant systemic therapy So it’s really hard to give adjuvant therapy when there’s no survival benefit, and you see that the toxicity is so bad. From my standpoint, it’s very hard for me to think about let’s take a patient, let’s remove all of their disease, and then give them immunotherapy. Let’s boost the immune system. Oh—but I already took it all out. So the adjuvant therapy idea is hard for me. (Participant 2) We know with the Keynote 716 trial, pembrolizumab can be [used] in patients who have high risk stage II disease. Based on that trial, we are now recommending adjuvant immune therapy. So it’s kind of a continuum. Now we can justify [stage] IIIA patients that were excluded from the stage III trials. (Participant 15) A lot of these patients are going to get adjuvant therapy, no matter what, so both for immunotherapy and for like a dabrafenib or trametinib treatment. The question is not whether or not we do adjuvant therapy, the question is whether they get the [adjuvant] therapy with or without a completion lymphadenectomy. (Participant 10) CONCLUSION: Opportunities exist to improve multidisciplinary melanoma care through broader consensus of how to translate emerging data into patient care and delineating surveillance roles.

Sentinel Lymph Node Gene Expression Signature Predicts Recurrence-Free Survival in Cutaneous Melanoma.

Simple SummaryDespite a negative SLN status, patients with Stage IIB/IIC melanoma demonstrate poor melanoma-specific survival when compared to Stage IIIA patients. In this study, we hypothesized that a molecular profile at the level of the SLN would provide potential insights into risk of disease recurrence and serve as a prognostic biomarker of patient outcomes regardless of the presence of SLN melanoma metastases. Gene expression profiling was performed on SLN biopsies using U133A 2.0 Affymetrix gene chips. Our study suggests a novel 12-gene SLN signature risk score which may predict disease recurrence in cutaneous melanoma patients managed with wide excision of the primary tumor and SLN biopsy.We sought to develop a sentinel lymph node gene expression signature score predictive of disease recurrence in patients with cutaneous melanoma. Gene expression profiling was performed on SLN biopsies using U133A 2.0 Affymetrix gene chips. The top 25 genes associated with recurrence-free survival (RFS) were selected and a penalized regression function was used to select 12 genes with a non-zero coefficient. A proportional hazards regression model was used to evaluate the association between clinical covariates, gene signature score, and RFS. Among the 45 patients evaluated, 23 (51%) had a positive SLN. Twenty-one (46.7%) patients developed disease recurrence. For the top 25 differentially expressed genes (DEG), 12 non-zero penalized coefficients were estimated (CLGN, C1QTNF3, ADORA3, ARHGAP8, DCTN1, ASPSCR1, CHRFAM7A, ZNF223, PDE6G, CXCL3, HEXIM1, HLA-DRB). This 12-gene signature score was significantly associated with RFS (p < 0.0001) and produced a bootstrap C index of 0.888. In univariate analysis, Breslow thickness, presence of primary tumor ulceration, SLN positivity were each significantly associated with RFS. After simultaneously adjusting for these prognostic factors in relation to the gene signature, the 12-gene score remained a significant independent predictor for RFS (p < 0.0001). This SLN 12-gene signature risk score is associated with melanoma recurrence regardless of SLN status and may be used as a prognostic factor for RFS.