Prognostic factors and outcomes of adult spermatic cord sarcoma. A study from the French Sarcoma Group

PurposeTo evaluate the outcomes of adult patients with spermatic cord sarcoma (SCS).MethodsAll consecutive patients with SCS managed by the French Sarcoma Group from 1980 to 2017 were analysed retrospectively. Multivariate analysis (MVA) was used to identify independent correlates of overall survival (OS), metastasis-free survival (MFS), and local relapse-free survival (LRFS).ResultsA total of 224 patients were recorded. The median age was 65.1 years. Forty-one (20.1%) SCSs were discovered unexpectedly during inguinal hernia surgery. The most common subtypes were liposarcoma (LPS) (73%) and leiomyosarcoma (LMS) (12.5%). The initial treatment was surgery for 218 (97.3%) patients. Forty-two patients (18.8%) received radiotherapy, 17 patients (7.6%) received chemotherapy. The median follow-up was 5.1 years. The median OS was 13.9 years. In MVA, OS decreased significantly with histology (HR, well-differentiated LPS versus others = 0.096; p = 0.0224), high grade (HR, 3 versus 1–2 = 2.7; p = 0.0111), previous cancer and metastasis at diagnosis (HR = 6.8; p = 0.0006). The five-year MFS was 85.9% [95% CI: 79.3–90.6]. In MVA, significant factors associated with MFS were LMS subtype (HR = 4.517; p < 10-4) and grade 3 (HR = 3.664; p < 10-3). The five-year LRFS survival rate was 67.9% [95% CI: 59.6–74.9]. In MVA, significant factors associated with local relapse were margins and wide reresection (WRR) after incomplete resection. OS was not significantly different between patients with initial R0/R1 resection and R2 patients who underwent WRR.ConclusionsUnplanned surgery affected 20.1% of SCSs. A nonreducible painless inguinal lump should suggest a sarcoma. WRR with R0 resection achieved similar OS to patients with correct surgery upfront.     

Deterioration in Health-Related Quality of Life Diminishes Benefit of Lung Cancer Resection in Older Adults

IntroductionOutcomes of oncologic resection are related to tumor biology and patient-reported health factors. However, data regarding changes in functional status and health-related quality of life (HRQOL) before and after lung surgery for older adults are lacking.Patients and MethodsWe identified lung cancer patients from the Surveillance, Epidemiology, and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) linked database. HRQOL surveys captured physical/mental health, activity of daily living (ADLs), and medical comorbidities. Patients who underwent surgery with baseline prediagnosis HRQOL survey and postdiagnosis follow-up survey were selected. Patient, disease, and HRQOL measures were analyzed by Cox proportional hazards regression for overall and disease-specific survival.ResultsOverall, 138 patients were evaluated. Disease extent was localized for 75 (54%) and regional for 58 (42%). The cohort experienced an increase in the number of major comorbidities and declines in physical HRQOL, mental HRQOL, and ADLs. Median overall survival was 74 months. Decreased overall survival was independently associated with male sex (hazard ratio [HR] = 1.7, P = .03), more advanced disease (regional vs. localized: HR = 1.8, P = .01; distant vs. localized: HR = 2.1, P = .22), and decline in ADLs (HR = 1.8, P = .02). Decreased disease-specific survival was independently associated with male sex (HR = 2.2, P = .03), more advanced disease (regional vs. localized: HR = 2.9, P = .002; distant vs. localized: HR = 3.1, P = .22), and decline in mental HRQOL (odds ratio = 2.1, P = .02).ConclusionThe potential survival benefit of lung resection for malignancy is diminished by declines in physical and mental health. Among older surgical patients at risk for functional and HRQOL deterioration, identification and mitigation of such deterioration may optimize oncologic outcomes.     

Contemporary Comparison of Clinicopathologic Characteristics and Survival Outcomes of Prostate Ductal Carcinoma and Acinar Adenocarcinoma: A Population-Based Study

PurposeTo investigate clinicopathologic characteristics and cancer-specific mortality (CSM) rates of ductal carcinoma (DC) versus the common acinar adenocarcinoma in nonmetastatic and metastatic (M1) prostate cancer patients.Patients and MethodsWithin the Surveillance, Epidemiology, and End Results database (2004-2015), we identified patients with histologically confirmed prostate adenocarcinoma who harbored either DC (n = 581) or acinar adenocarcinoma (n = 489,296). Kaplan-Meier and 4:1 propensity score–matched multivariable Cox regression models adjusted for clinical and pathologic parameters were used to test for CSM differences. Three separate analyses were performed on all patients with nonmetastatic disease, patients with nonmetastatic patients treated with radical prostatectomy only, and patients with metastatic disease.ResultsDC was identified in 502 (0.10%) of 469,946 patients with nonmetastatic disease and 79 (0.39%) of 19,931 patients with metastatic disease. In patients with nonmetastatic disease, 253 (50.4%) DC patients underwent radical prostatectomy, 61 (12.2%) DC patients received external-beam radiotherapy, and 188 (37.4%) received other treatment modalities. In multivariable analyses, DC was associated with higher CSM in the overall nonmetastatic patient population (hazard ratio [HR] = 1.8; 95% confidence interval [CI], 1.3-2.6; P = .001), in the nonmetastatic radical prostatectomy population (HR = 2.8; 95% CI, 1.3-6.0; P < .01), and in the M1 population (HR = 1.6; 95% CI, 1.1-2.2; P < .01).ConclusionProstate cancers of ductal origin represent a rare entity among patients with nonmetastatic disease as well as among patients with metastatic disease, and regardless of stage, DC behaves more aggressively.     

Effect of Thoracic Radiotherapy Timing and Fractionation on Survival in Nonmetastatic Small Cell Lung Carcinoma

BackgroundThe optimal timing of thoracic radiation therapy (RT) in relation to chemotherapy is unknown in the treatment of nonmetastatic small cell lung cancer (SCLC). We analyzed the National Cancer Data Base (NCDB) to assess the effect on overall survival (OS) of RT timing with chemotherapy for patients with SCLC.Materials and MethodsThe NCDB was queried for patients diagnosed with nonmetastatic SCLC from 1998 to 2011 who had undergone definitive chemoradiation. The patients were stratified into quartiles according to the interval between the start of chemotherapy and the start of RT. The first and second quartiles (RT started 0-20 days after chemotherapy) were classified as “early” RT and the third and fourth quartiles (RT started 21-126 days after chemotherapy) as “late” RT. Patients were included if they had received hyperfractionated 45 Gy in 30 fractions or standard fractionation of ≥ 60 Gy in 1.8- to 2-Gy fractions. Kaplan-Meier analyses of OS were performed, and multivariable Cox regression analysis was conducted to assess the effect of the covariates on OS.ResultsA total of 8391 patients were included (50.5% had received early RT). Early RT was associated with significant improvement in survival (5-year OS, 21.9% vs. 19.1%; P = .01). On subgroup analysis, the survival advantage for early RT was significant for patients receiving hyperfractionated RT (5-year OS, 28.2% vs. 21.2%; P = .004) but not for those receiving standard fractionation (19.8% vs. 18.4%; P = .29). On multivariable Cox regression analysis, hyperfractionated RT was associated with reduced mortality (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.85-0.96; P = .001), but early RT was not (HR, 0.98; 95% CI, 0.94-1.04; P = .53).ConclusionThese data support the early initiation of hyperfractionated thoracic RT for nonmetastatic SCLC.     

Outcomes for Young Men With Localized Intermediate-Risk Prostate Cancer: An Analysis of the NCDB

BackgroundPrimary management of localized, intermediate-risk prostate cancer consists of radical prostatectomy (RP), radiotherapy (RT) with short-course androgen deprivation therapy (ADT), or RT alone. The purpose of this study was to determine if these treatment strategies have equivalent overall survival (OS) in patients < 55 years old with intermediate-risk prostate cancer.Patients and MethodsWe identified 35,134 patients in the National Cancer Data Base with localized intermediate-risk prostate cancer treated with RP, RT + ADT, or RT from 2004 to 2013. Ten-year OS rates were estimated by the Kaplan-Meier method. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were computed by multivariate Cox regression.ResultsA total of 29,920 patients (85.2%) underwent RP, 1393 (4.0%) RT + ADT, and 3821 (10.9%) RT. Median patient age was 51 years old, and median follow-up was 59.9 months. Ten-year OS was estimated to be 94.2% for RP, 80.7% for RT + ADT, and 85.2% for RT (P < .0001). On multivariate analysis, treatment with RT + ADT or RT was associated with significantly worse OS compared to treatment with RP (RT + ADT HR = 2.06, 95% CI 1.67-2.54, P < .0001; RT HR = 2.0, 95% CI 1.71-2.33, P < .0001). Patients who met all 3 of the intermediate-risk criteria showed worse OS compared to patients who met only one criterion (HR = 1.80; 95% CI, 1.32-2.44; P = .0002).ConclusionRP is significantly more likely than RT + ADT or RT to be used as a primary treatment for young men with localized intermediate prostate cancer. RP was also associated with improved OS compared to RT + ADT and RT.     

Surgical Prognosis of Synchronous Multiple Primary Lung Cancer: Systematic Review and Meta-Analysis

BackgroundWe evaluated the long-term prognosis of synchronous multiple primary lung cancer (SMPLC) patients after surgical treatment and explored prognostic factors for overall survival (OS).Materials and MethodsA systematic review and meta-analysis was performed regarding the surgical prognosis of SMPLC. A literature search was performed using online databases. All studies were rigorously categorized following the 8th edition of the tumor, node, metastasis classification (TNM) staging rules for multiple lung cancers: SMPLC and multifocal ground-glass/lepidic (GG/L) lung cancers. Five-year OS after surgery was pooled, and hazard ratios (HRs) for prognostic factors were synthesized. Specific subgroup analysis and sensitivity analysis were conducted (PROSPERO registration CRD42019142420).ResultsAn analysis of 26 studies including 1788 patients was performed. The pooled 5-year OS was 45% (95% confidence interval [CI], 37-53) of true SMPLC patients and 62% (95% CI, 57-67) of patients with pathologic stage I disease, which was different from the 5-year OS of 93% (95% CI, 85-100) of patients with multifocal GG/L lung cancers. Poor prognostic factors for SMPLC were lymph node metastasis (HR = 2.36; 95% CI, 1.75-3.20; P < .001) and pneumonectomy (HR = 2.96; 95% CI, 1.36-6.45; P = .006], whereas histology (HR = 1.11; 95% CI, 0.82-1.50; P = .508), laterality (HR = 1.16; 95% CI, 0.93-1.44, P = .190), sublobar resection (HR = 1.29; 95% CI, 0.90-1.84; P = .159), and adjuvant therapy (HR = 1.07; 95% CI, 0.64-1.80; P = .791) were not found to influence the outcome.ConclusionThe long-term prognosis of SMPLC patients after surgery is acceptable, especially in patients with early-stage disease. Sublobar resection can be applied, although pneumonectomy should be avoided. Advanced criteria are needed to diagnose SMPLC and distinguish it from multifocal GG/L lung cancer to perform accurate surgical evaluation.     

Aggressive Surgical Excision of Supraclavicular Lymph Node Did Not Improve the Outcomes of Breast Cancer With Supraclavicular Lymph Node Involvement (KROG 16-14)

IntroductionThe purpose of this study was to evaluate the outcomes of upfront surgery followed by radiation therapy (RT) for ipsilateral supraclavicular (SCN) and/or internal mammary (IMN) node-positive breast cancer.Materials and MethodsOne hundred fifty-eight patients were included; among these, 91 patients were SCN-positive, 54 were IMN-positive, and 13 were SCN- and IMN-positive. Patients underwent breast conserving surgery (n = 74) or mastectomy (n = 84) followed by systemic therapy, and adjuvant RT to whole breast/chest wall with or without regional nodal RT. Regarding regional treatments for SCN and IMN, SCN excision was performed in 59 (37.3%) patients, IMN excision in 10 (6.3%) patients, SCN RT in 143 (90.5%) patients, and IMN RT in 68 (43.0%) patients.ResultsThe median duration of follow-up was 72 months (range, 7-182 months). There were 20 locoregional recurrences and 45 distant metastases. In-field failure was observed only in SCN (n = 8), and 6 of these patients initially underwent SCN excision. The 5-year locoregional recurrence-free survival, disease-free survival (DFS), and overall survival rates were 87.3%, 71.6%, and 89.7%, respectively. Neither SCN excision nor SCN RT dose ≥ 54 Gy improved locoregional control (P = .927 and P = .693, respectively) or DFS (P = .394 and P = .686, respectively). Having ≥ 10 involved axillary lymph nodes was the only independent prognosticator for DFS after adjusting for covariates (P = .003).ConclusionRegional control rate in initially involved SCN and/or IMN was acceptable in patients treated with upfront surgery followed by systemic therapy plus adjuvant RT. More aggressive regional therapy such as SCN excision did not improve locoregional control or survival.     

De-escalating Locoregional Therapy for Axillary Micrometastases in Breast Cancer: How Much is Too Much?

BackgroundThe applicability of modern prospective data on adjuvant radiotherapy (RT) fields in patients with micrometastases is limited because many trials occurred prior to routine measurement of nodal metastasis size and modern sentinel lymph node evaluation techniques. We aimed to determine prognostic factors for patients with micrometastases and evaluate the impact of adjuvant RT on disease outcomes.Patients and MethodsPatients diagnosed with pathologic T1-T3 N1mi breast cancers between 2004-2015 were identified. Cox proportional hazards methods were used to determine characteristics predictive of locoregional recurrence (LRR). Tumor and treatment-specific factors were further evaluated using log-rank statistics to compare rates of LRR-free survival.ResultsThis analysis included 156 patients. On multivariable analysis, grade 3 histology (HR 10.84, 95% CI 2.72-43.21) and adjuvant RT (HR 0.22, 95% CI 0.06-0.81) were independent predictors of LRR. Among patients with grade 1-2 histology, 5-year LRR-free survival was 98.8% in patients who received adjuvant RT versus 100% in patients who did not receive adjuvant RT (P = .82). Among patients with grade 3 histology, 5-year LRR-free survival was 90.1% in patients who received adjuvant RT versus 53.0% in patients who did not receive adjuvant RT (P = .025), and 100% in patients receiving comprehensive nodal irradiation versus 76.7% in patients receiving whole breast irradiation or no RT (P = .045).ConclusionPatients with grade 3 micrometastases are at substantial risk for LRR. Adjuvant RT, including comprehensive nodal irradiation, should be strongly considered in these women.     

Regional Nodal Irradiation for Clinically Node-Positive Breast Cancer Patients With Pathologic Negative Nodes After Neoadjuvant Chemotherapy

IntroductionNeoadjuvant chemotherapy (NAC) is increasingly used for operable breast cancer (BC). Appropriate radiation therapy (RT) fields (ie, whole breast [WB] ± regional nodal irradiation [RNI]) in patients who were clinically node positive (cN1) but convert to pathologically node negative (ypN0) after NAC are unknown and the subject of the accruing NSABP B-51 trial. We sought to compare outcomes between WB RT with or without RNI following breast conservation and sentinel lymph node biopsy (SLNB) alone in cN1, ypN0 women following NAC.Patients and MethodsWe identified all BC patients with cN1, ypN0 who underwent NAC followed by lumpectomy and SLNB between 2006 and 2015 in the National Cancer Database. RNI utilization was evaluated using Cochran-Armitage test. Overall survival between WB RT alone versus WB + RNI was compared using Kaplan-Meier with and without propensity score-based weighted adjustment and multivariable (MVA) Cox proportional hazards.ResultsFrom 2006 to 2015, RNI use increased from 48.13% to 62.13% (Pfor trend <.001). The 10-year survival for WB alone versus WB + RNI was 83.6% and 79.5%, respectively (P= .14). On MVA analysis, the addition of RNI compared to WB alone was not associated with a survival benefit (WB vs. WB + RNI: hazard ratio 0.80, 95% confidence interval, 0.58-1.11, P= .19). Results were unchanged after propensity score-based adjustment.ConclusionFor women with cN1 BC who convert to ypN0 following NAC and breast conserving surgery with SLNB alone, more extensive RNI may not provide a long-term survival benefit. Prospective validation via the NSABP B-51 trial will be essential.     

Effectiveness of Combining Bevacizumab With First-Line Chemotherapy Regimens for Metastatic Colorectal Cancer in Real-World Practice

BackgroundAnti–vascular endothelial growth factor (VEGF) agents have shown clinical benefits against metastatic colorectal cancer (mCRC) when combined with cytotoxic chemotherapeutic drugs. Because randomized controlled trials have restrictive enrollment criteria, and because the participants typically do not resemble actual patients, we here investigated the efficacy of bevacizumab as part of a combination therapy for mCRC in a Korean real-world practice setting.Patients and MethodsWe retrospectively evaluated 3748 patients with an initial diagnosis of mCRC or recurrent colorectal cancer with distant metastasis who received first-line chemotherapy in a tertiary cancer center. The primary study endpoint was overall survival. We used multivariate analysis using the Cox regression hazard model and propensity score matching (PSM) methods to adjust for any confounding clinicopathologic factors. Subgroup analysis was also performed for patients who did not receive local treatments for metastatic lesions before receipt of first-line chemotherapy.ResultsIn an initial crude analysis, patients who received first-line FOLFOX or FOLFIRI showed better survival outcomes if these regimens were combined with bevacizumab (median overall survival, 3.5 vs. 2.3 years; hazard ratio [HR] = 0.66; 95% confidence interval [CI], 0.59-0.73; P < .001). However, Cox regression hazard model adjusted analysis using PSM methods revealed no significant survival differences between these groups (3.0 vs. 2.6 years; HR = 0.92; 95% CI, 0.79-1.07; P = .2612). We performed further survival analysis of 2814 patients with unresectable disease without metastasectomy who received metastatic radiofrequency ablation before chemotherapy. Cox regression and PSM analysis indicated that bevacizumab group showed better survival (HR = 0.82; 95% CI, 0.71-0.94; P = .005; and HR = 0.84; 95% CI, 0.71-0.99; P = .018).ConclusionThe addition of bevacizumab to a first-line chemotherapeutic regimen provides survival benefits in a real-world setting for mCRC patients who cannot undergo curative-intent local treatment for metastatic lesions.     

Diabetes and the Prognosis in Patients With Non-Hodgkin Lymphoma: A Meta-analysis of Cohort Studies

BackgroundConsensus lacks regarding the association between diabetes mellitus (DM) and the prognosis of patients with non-Hodgkin lymphoma (NHL). We aimed to systematically evaluate the above association, as well as the potential influence of metformin use in a meta-analysis of cohort studies.Materials and MethodsCohort studies investigating the association between DM and survival outcomes of patients with NHL were included by search of electronic databases that included PubMed, Embase, and Web of Science. A random-effects model was adopted to combine the results.ResultsEight cohort studies including 8652 patients with NHL were analyzed. Compared to non-DM patients with NHL, DM was associated with poor overall survival (OS, hazard ratio [HR] = 1.49, 95% confidence interval [CI]: 1.18-1.89, P < .001, I² = 69%), progression-free survival (PFS, HR = 1.30, 95% CI: 1.09-1.56, P = .004, I² = 0%), and lymphoma-specific survival (LSS, HR = 1.86, 95% CI: 1.41-2.45, P < .001, I² = 0%). Subgroup analysis showed consistent results in patients with diffuse large B-cell lymphoma (DLBCL, HR = 1.42, 1.35, and 1.95 for outcomes of OS, PFS, and LSS, respectively; P values all <.05). However, the associations between DM and these survival outcomes became nonsignificant in subgroup analysis limited to DM patients with concurrent use of metformin (HR = 1.30, 1.12, and 1.43 for outcomes of OS, PFS, and LSS, respectively; P values all > .10).ConclusionsDM is associated with poor survival outcomes in patients with B-cell NHL, which is consistent in patients with DLBCL. Concurrent metformin use in DM patients with NHL may be associated with improved survival outcomes.     

Angiogenic and Antiangiogenic VEGFA Splice Variants in Colorectal Cancer: Prospective Retrospective Cohort Study in Patients Treated With Irinotecan-Based Chemotherapy and Bevacizumab

BackgroundAlternative splicing of vascular endothelial growth factor A (VEGFA) results in VEGFAxxxb antiangiogenic isoforms that fail to activate angiogenesis. Bevacizumab, widely used in patients with metastatic colorectal cancer (CRC), binds both VEGFA and VEGFAxxxb isoforms.Patients and MethodsFormalin-fixed, paraffin-embedded primary tumors from metastatic CRC patients treated with first-line FOLFIRI (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) + bevacizumab (n = 285) or FOLFIRI only (n = 75) were collected. The relative expression of VEGFA121a, 121b, 145a, 145b, 165a, and 165b was assessed with custom TaqMan-MGB assays and quantitative PCR.ResultsAt a median follow-up of 101.5 months, left-sided primary CRC was a favorable prognosticator (median survival, 29.2 vs. 18.2 months; P = .015). Positive high VEGFA145b was an unfavorable factor for progression-free survival (PFS; hazard ratio [HR] = 1.66; 95% confidence interval [CI], 1.13-2.44; P = .009) in patients who received FOLFIRI + bevacizumab, without prognostic significance in FOLFIRI-only patients (HR = 0.70; 95% CI, 0.34-1.44; P = .33). The adverse effect on PFS of 145b was more pronounced in patients with right-sided colon cancer (HR = 2.62; 95% CI, 1.35-5.12; P = .005), especially in those who received bevacizumab (HR = 2.85; 95% CI, 1.31-6.21; P = .008). In patients with right-sided colon primary tumors, isoform 121b correlated with inferior PFS (HR = 1.73; 95% CI, 0.94-3.18; P = .076) and overall survival (OS; HR = 2.0; 95% CI, 1.08-3.72; P = .028). In patients with left-sided primary tumors, positive high 165b correlated with superior PFS (HR = 0.76; 95% CI, 0.59-0.99; P = .044) and OS (HR = 0.68; 95% CI, 0.52-0.90; P = .006). At multivariate analysis, right-sided primary tumor was associated with inferior PFS (HR = 1.28; 95% CI, 1.00-1.64), while 145b consistently retained predictive significance for lack of benefit in PFS with bevacizumab (HR = 1.71; 95% CI, 1.16-2.53). Multivariate analysis for OS showed that VEGFA165b expression was favorable in patients with left-sided but unfavorable in patients with right-sided primary tumors (P_interaction < .001).ConclusionThe antiangiogenic isoform VEGFA145b messenger RNA may predict resistance to bevacizumab. Differences in biological relevance and prognostic significance of various VEGFA isoforms were found for right- versus left-sided primary tumors.     

Prognostic Role of Low-Skeletal Muscle Mass on Staging Computed Tomography in Metastasized Colorectal Cancer: A Systematic Review and Meta-Analysis

BackgroundLow-skeletal muscle mass (LSMM) is defined as skeletal muscle loss, which can be assessed by imaging. Our aim was to establish the effect of LSMM on overall survival (OS) in metastasized colorectal cancer patients based on a large patient sample.Patients and MethodsMEDLINE library, EMBASE, and SCOPUS databases were screened for the associations between LSMM and mortality in metastasized colorectal cancer patients up to March 2022. The primary aim of the systematic review was to investigate the influence of LSMM on overall survival (OS) by means of the effect of measure hazard ratio. Fifteen studies were included into the present analysis.ResultsThe included studies comprised 1744 patients. The frequency of LSMM was 46.2%. Associations between LSMM and OS were as follows: hazard ratio (HR) = 1.34 (95% confidence interval [CI] 0.94-1.91), P = .10 in univariable analysis and HR = 2.05 (95% CI 1.18-3.56), P = .01 in multivariable analysis. LSMM influenced OS in patients undergoing first-line chemotherapy, HR = 1.51 (95% CI 1.20-1.89), P = .0004. In patients undergoing second- and third-line chemotherapy, LSMM was not associated with OS, HR = 1.43 (95% CI 0.65-3.14), P = .37 Also, LSMM did not affect OS in patients with resection of hepatic metastases, HR = 0.93 (95% CI 0.70-1.24), P = .63. LSMM tended to affect progression-free survival, HR = 1.49 (95% CI 0.94-2.35), P = .09. LSMM did not predict treatment toxicity, odds ratio (OR) = 1.52 (95% CI 0.84-2.72), P = .16.ConclusionLSMM occurs in 46.2% of patients with metastasized colorectal cancers. LSMM is associated with OS in patients undergoing first-line chemotherapy. LSMM does not affect OS in second- and third-line chemotherapy and in patients undergoing resection of hepatic metastases. LSMM is not associated with progression-free survival and treatment toxicity.     

The Significance of Lymph Node Ratio and Total Lymph Nodes Examined in Determining the Indications of Adjuvant Radiation in pN2 Non–small Cell Lung Cancer

Introduction/BackgroundPast studies have shown mixed results of postoperative radiation (PORT) for pN2 NSCLC patients. We hypothesize that PORT can improve overall survival (OS) in pN2 NSCLC patients with high lymph node ratio (LNR).Materials/MethodsThe National Cancer Database was queried for non-metastatic pN2 NSCLC patients with R0 surgery and adjuvant chemotherapy from 2004 to 2016. Cox models were used to assess the impact of PORT and LNR on OS adjusted for patient characteristics and treatment information.ResultsAmong 4,050 patients, 1,728 (42.7%) had PORT. There was increased use of IMRT in the more recent period (53.8% in 2010-2016 vs 24.0% in 2004-2009). PORT was associated with better OS in the overall cohort. For patients with inadequate lymph node dissection (LND), PORT marginally improved OS (HR = 0.91, p = 0.058). Among patients with adequate LND, PORT did not improve OS for patients with LNR <15% (HR = 1.11, p = 0.21), or LNR 15-29% (HR = 1.03, p = 0.73), but it significantly improved OS for patients with LNR ≥30% (HR = 0.83, p = 0.006). In patients with LNR≥30%, IMRT significantly improved OS when compared to no PORT (HR = 0.75, p < 0.05) while 3D RT did not (HR = 0.89, p = 0.32).ConclusionsPORT was associated with better survival for pN2 NSCLC patients after R0 resection, adequate LND with high LNR, after accounting for multiple confounders. Among the whole cohort, most of the OS benefits of PORT were driven by patients with inadequate LND, high LNR or use of IMRT.     

Nomograms for Metastasis-Free and Overall Survival for Pathologically Node Positive Prostate Cancer Patients Treated With or Without Radiation Therapy Plus Short-Term ADT

Purpose/ObjectivesWe aimed to develop nomograms to predict the risk reduction for metastasis and death in pathologically node-positive (pN +) prostate cancer patients treated with or without radiation therapy (RT).Materials/MethodsFrom a prospectively gathered institutional database, we identified patients with pN + M0 prostate cancer after surgery. We evaluated several regression models of known or suspected clinical-pathologic covariates and selected the model with the highest Harrell's concordance-index (c-index) and clinical utility to prognosticate metastasis for inclusion in a nomogram. Covariates in the final, competing-risk adjusted, metastasis model included PSA nadir after surgery, pathologic T-stage, margin status, Gleason score (GS), number of positive lymph nodes, and use of postoperative radiotherapy combined with androgen deprivation therapy (RT + ADT). The overall survival model also included Charlson comorbidity score and age.Results336 pN + men with a mean age of 64.9 years and a median follow-up of 4.1 years who had a radical prostatectomy were included in the analysis. 83 men were recommended RT + ADT, of whom 4% refused the ADT and received RT alone. C-index was 0.85 and 0.71 for the MFS and OS models, respectively. On multivariable analysis (MVA) adjusted for competing risks, RT + ADT significantly improved MFS (HR=0.70 P = < .01) with number of nodes positive, GS 8-10, PSA nadir > 1 ng/mL, and pT3b prognostic for metastasis. MVA for OS demonstrates RT+ADT improves survival (HR=0.40, P = .02), with GS8-10 and PSA nadir > 1.0 prognostic for death.ConclusionWe developed predictive nomograms for patients with pN+ prostate cancer following radical prostatectomy. These models can discretely quantify an individual's risk of metastasis or death with and without post-prostatectomy radiotherapy.     

Improved Overall Survival With Comprehensive Local Consolidative Therapy in Synchronous Oligometastatic Non–Small-Cell Lung Cancer

BackgroundLocal consolidative therapy (LCT) to optimize disease control is an evolving management paradigm in non–small-cell lung cancer (NSCLC) patients who present with a limited metastatic disease burden. We hypothesized that LCT to all sites of disease would be associated with improved overall survival (OS) among patients with synchronous oligometastatic NSCLC.Patients and MethodsPatients presenting to a single institution (2000-2017) with stage IV NSCLC and ≤ 3 synchronous metastases were identified. Intrathoracic nodal disease was counted as one site. Landmark and propensity-adjusted Cox regression analyses were performed to identify factors associated with OS.ResultsOf 194 patients, 143 (74%) had 2 or 3 sites of metastasis. LCT was delivered to all sites of disease in 121 patients (62%), to some but not all sites in 52 (27%), and were not used in 21 (11%). Comprehensive LCT was independently associated with improved OS (hazard ratio [HR] = 0.67; 95% confidence interval [CI], 0.46-0.97; P = .034), with the greatest therapeutic effect among patients without thoracic nodal disease, bone metastases, or > 1 metastatic site. Among patients who underwent comprehensive LCT, tumor histology (squamous: HR = 2.32; 95% CI, 1.28-4.22; P = .006), intrathoracic disease burden (T3-4: HR = 1.67; 95% CI, 0.97-2.86; P = .065; N3: HR = 1.90; 95% CI, 0.90-4.03; P = .093), and bone metastases (HR = 1.74; 95% CI, 1.02-3.00; P = .044) were associated with poor OS.ConclusionComprehensive LCT was associated with improved OS in this large cohort of patients with synchronous oligometastatic NSCLC. These results support ongoing prospective efforts to characterize the therapeutic benefits associated with this management strategy.     

Utilization of Hypofractionated Whole-Breast Radiotherapy With Concurrent Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Therapy

IntroductionHypofractionated radiotherapy (Hypo-RT) is now considered the standard of care for the majority of patients receiving whole-breast irradiation (WBI). However, there are few data on the use of Hypo-RT in human epidermal growth factor receptor 2 (HER2)-positive patients receiving concurrent anti-HER2 therapy. In this study, we sought to examine patterns of WBI in HER2-positive patients.Patients and MethodsUsing the National Cancer Data Base, we identified women with nonmetastatic HER2-positive breast cancer diagnosed between 2010 and 2015 who received WBI. The Hypo-RT group was defined as those receiving 21 or fewer fractions. All other patients were in the conventional radiotherapy (RT) group. Multivariate logistic regression was used to identify predictors of Hypo-RT utilization. Five-year overall survival was estimated by the Kaplan-Meier method.ResultsThe study included 15,776 patients, of whom 17.7% received Hypo-RT. The rate of Hypo-RT utilization increased from 7.4% in 2010 to 29.3% in 2015 (P = .004). Predictors of Hypo-RT use included older age (≥60 vs. < 60 years), higher median income quartile, further distance from the treatment facility (>50 vs. ≤50 miles), treatment at an academic facility, and later year of diagnosis. Unadjusted 5-year overall survival rates were similar among patients who received Hypo-RT and conventional RT (93.9% vs. 95.2%, P = .26). After adjusting for patient, facility, and tumor variables, Hypo-RT was not significantly associated with survival.ConclusionAlthough Hypo-RT was not commonly delivered in patients with HER2-positive breast cancer, the utilization rate quadrupled over the study period. Multiple socioeconomic and clinical predictors of Hypo-RT receipt were identified. Adjuvant RT regimen was not significantly associated with overall survival.     

The efficacy of anatomic resection for hepatocellular carcinoma within Milan criteria: A retrospective single-institution case-matched study

IntroductionStill now, the efficacy of anatomic resection (AR) for hepatocellular carcinoma (HCC) is controversial. The aim of this study is to examine it in our cohort and detect an optimal indicator for AR.MethodsThe present study included 656 patients with primary HCC within Milan criteria who underwent hepatectomy from 2000 to 2019. Our cohort was divided into AR (n = 378) and non-anatomic resection (NAR) (n = 278) groups, and 1:1 propensity score matching (PSM) was performed to minimize the effect of potential confounders. Recurrence-free survival (RFS), overall survival (OS), and a preoperative indicator for AR were examined.Results210 patients from each group were well-matched, and preoperative confounding factors were balanced between the two groups. There was no significant difference in RFS and OS between the two groups before (RFS; HR = 0.89 P = 0.25, OS; HR = 1.08 P = 0.64) and after PSM (RFS; HR = 0.93 P = 0.60, OS; HR = 1.07 P = 0.75). Subgroup analysis showed that the survival improvement effect of AR was observed in cases with a fucosylated fraction of alfa-fetoprotein (AFP-L3) > 10% and poorly differentiation (P for interaction <0.05). Moreover, the logistic regression analysis showed that preoperative AFP-L3 > 10% was an independent predictor for poorly differentiation (OR = 2.58, P = 0.03).ConclusionThe efficacy of AR for patients with primary HCC within Milan criteria was not shown. But it was suggested that AFP-L3 > 10% might be a preoperative indicator of AR for HCC within Milan criteria.     

Adherence to Guideline Recommendations for Perioperative Chemotherapy in Patients with pN2-3 M0 Squamous Cell Carcinoma of the Penis: Temporal Trends and Survival Outcomes

AimsTo analyse contemporary perioperative chemotherapy (CHT) guideline adherence rates for pN2-3 M0 squamous cell carcinoma of the penis, as well as CHT association with cancer-specific (CSM) and other-cause mortality (OCM).Materials and methodsWithin the Surveillance, Epidemiology, and End Results databases, 311 pN2-3 M0 squamous cell carcinoma of the penis patients treated with inguinal lymph node dissection were identified. Univariable and multivariable logistic regression analyses focused on CHT rates, whereas cumulative incidence plots and multivariable competing risks regression analyses tested for CSM and OCM rates.ResultsCHT was administered to 140 (45%) patients and rates increased from 37.5 to 62.2% (2004–2015; P = 0.02). Specifically, annual CHT rates increased over time in patients younger or equal to 65 years and in patients older than 65 years (44.4–84.6% versus 28.6–50%, respectively), but this trend was not statistically significant (P = 0.1 and P = 0.2, respectively). The median follow-up was 13 months for both CHT (interquartile range 8.0–32.2) and no-CHT subgroups (interquartile range 5.0–40.0). In multivariable logistic regression analyses, more contemporary year of diagnosis interval (odds ratio 2.08, P < 0.01) and age older than 75 years (odds ratio 0.14, P < 0.001) were independent predictors of CHT use. In multivariable competing risks regression analyses, CHT use did not affect CSM (hazard ratio 1.02; P = 0.7) or OCM (hazard ratio 1.56; P = 0.8).ConclusionsCHT adherence rates sharply increased in the most recent years. Despite this increase over time, the lack of efficacy regarding CSM benefit is disappointing.     

Contemporary Assessment of Survival Rates in Stage I Testicular Seminoma: A Population-Based Comparison Between Surveillance and Active Treatment After Orchiectomy

BackgroundWe tested contemporary surveillance and active treatment (AT) that included chemotherapy (CHT) and radiotherapy (RT) rates for stage I testicular seminoma patients, as well as cancer-specific mortality (CSM) and other-cause mortality (OCM) rates.Patients and MethodsWithin the Surveillance, Epidemiology, and End Results database (1988-2015) we identified 11,206 stage I testicular seminoma patients. Surveillance versus CHT versus RT use rates were investigated using estimated annual percentage change (EAPC) analyses. After propensity score (PS) matching, cumulative incidence plots and multivariable competing risks regression models (MCRRMs) tested for CSM and OCM.ResultsOf all 11,206 patients, 4434 (40%), 918 (8%), and 5854 (52%), respectively, underwent surveillance, CHT, or RT after initial orchiectomy. Surveillance (EAPC: 7.5%; P < .001) and CHT (EAPC: 13.5%; P < .001) rates increased over time, whereas RT rates decreased (EAPC: ?3.8%; P < .001). After PS matching, in MCRRMs surveillance was an independent predictor of CSM, relative to AT (hazard ratio [HR], 2.59; P = .04). Conversely, surveillance versus AT did not affect OCM (HR, 1.52; P = .051). All other analyses that focused on CSM and OCM, namely surveillance versus RT, surveillance versus CHT, and RT versus CHT resulted in nonsignificant differences (all P > .5).ConclusionSurveillance and CHT use in stage I testicular seminoma rates increased, whereas RT rate decreased over time. A protective effect of AT defined as either RT or CHT was identified on CSM, relative to surveillance. This protective effect was not described for OCM. No differences in survival were recorded, when individual management strategies (surveillance vs. RT vs. CHT) were compared with each other.