Propensity Score-weighted Analysis Research Articles

Comparative effectiveness of proton versus photon chemoradiotherapy for patients with private insurance.

7049 Background: Proton therapy may increase the tolerability/efficacy of concurrent chemoradiotherapy (CRT) but is controversial & generally not covered by private insurers. There is little data on the comparative effectiveness (CE) of proton vs photon CRT among private insurance pts to guide payers on proton coverage policies. Methods: We conducted a CE study of adult non-metastatic cancer pts with private insurance treated with curative-intent proton vs photon CRT from 2011-2016 at Penn. The choice of radiation modality was heavily influenced by the insurer’s proton coverage policy. Data on adverse events (AEs) & survival were gathered prospectively using standardized templates. Primary endpoint was 90-day AEs associated with unplanned hospitalizations (CTCAEv4 grade ≥3 AEs). Secondary endpoints included 90-day grade ≥2 AEs, decline in ECOG performance status (PS) during treatment, disease-free survival (DFS) & overall survival (OS). Modified Poisson regression models with inverse propensity score weighting were used for adverse event outcomes. Weighted Cox proportional hazards models were used for survival outcomes. Propensity scores were estimated using an ensemble machine-learning approach. P<0.01 was significant. Results: 920 pts were included (178 proton/742 photon), with H&N(25 proton/296 photon); CNS(44/128); lung(41/120); upper GI(34/78) & lower GI/GYN(34/120). Median age was 57. Race, comorbidity score, BMI, baseline AEs & baseline PS were similar (p>0.05 for all). 11.2% of proton pts had grade ≥3 AE’s vs 26.8% of photon pts. On propensity score weighted-analyses, proton CRT was associated with significantly lower relative risk (RR) of 90-day grade ≥3 AEs (RR 0.51, 95%CI 0.32-0.81, p<0.01). 90-day grade ≥2 AE’s (RR 0.91, 95%CI 0.83-0.99, p=0.03); decline in PS (RR 0.85, 95%CI 0.70-1.04, p=0.11); DFS (HR 0.64, 95%CI 0.27-1.52, p=0.31) & OS (HR 0.53, 95%CI 0.18-1.52, p=0.24) favored protons. Sensitivity analysis showed that a substantial imbalance in an unmeasured confounder would be needed to alter the significance of the primary outcome. Proton accepting insurance status was not associated with a difference in 90-day grade ≥3 AE’s (RR 1.02, 95%CI 0.95-1.10, p=0.54) for pts treated with photon CRT (608 with non-proton accepting insurance & 134 with proton-accepting insurance). Conclusions: In adults with private insurance, proton CRT was associated with significantly reduced acute grade ≥3 AE’s with similar DFS & OS. Proton-accepting insurance status was not associated with better health outcomes when adjusting for RT modality.

Comparative Effectiveness of Antibiotic Treatment Duration in Children With Pyelonephritis

National guidelines recommend treating children with pyelonephritis for 7 to 14 days of antibiotic therapy, yet data are lacking to suggest a more precise treatment duration. To compare the clinical outcomes of children receiving a short-course vs a prolonged-course of antibiotic treatment for pyelonephritis. Retrospective observational study using inverse probability of treatment weighted propensity score analysis of data from 5 hospitals in Maryland between July 1, 2016, and October 1, 2018. Participants were children aged 6 months to 18 years with a urine culture growing Escherichia coli, Klebsiella species, or Proteus mirabilis with laboratory and clinical criteria for pyelonephritis. Treatment of pyelonephritis with a short-course (6 to 9 days) vs a prolonged-course (10 or more days) of antibiotics. Composite outcome of treatment failure within 30 days of completing antibiotic therapy: (a) unanticipated emergency department or outpatient visits related to urinary tract infection symptoms, (b) hospital readmission related to UTI symptoms, (c) prolongation of the planned, initial antibiotic treatment course, or (d) death. A subsequent urinary tract infection caused by a drug-resistant bacteria within 30 days was a secondary outcome. Of 791 children who met study eligibility criteria (mean [SD] age 9.2 [6.3] years; 672 [85.0%]) were girls, 297 patients (37.5%) were prescribed a short-course and 494 patients (62.5%) were prescribed a prolonged-course of antibiotics. The median duration of short-course therapy was 8 days (interquartile range, 7-8 days), and the median duration of prolonged-course therapy was 11 days (interquartile range, 11-12 days). Baseline characteristics were similar between the groups in the inverse probability of treatment weighted cohort. There were 79 children (10.1%) who experienced treatment failure. The odds of treatment failure were similar for patients prescribed a short-course vs a prolonged-course of antibiotics (11.2% vs 9.4%; odds ratio, 1.22; 95% CI, 0.75-1.98). There was no significant difference in the odds of a drug-resistant uropathogen for patients with a subsequent urinary tract infection within 30 days when prescribed a short-courses vs prolonged-course of antibiotics (40% vs 64%; odds ratio, 0.36; 95% CI, 0.09-1.43). The study findings suggest that short-course antibiotic therapy may be as effective as prolonged-courses for children with pyelonephritis, and may mitigate the risk of future drug-resistant urinary tract infections. Additional studies are needed to confirm these findings.

Empirical Anti-MRSA vs Standard Antibiotic Therapy and Risk of 30-Day Mortality in Patients Hospitalized for Pneumonia

Use of empirical broad-spectrum antibiotics for pneumonia has increased owing to concern for resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA). The association of empirical anti-MRSA therapy with outcomes among patients with pneumonia is unknown, even for high-risk patients. To compare 30-day mortality among patients hospitalized for pneumonia receiving empirical anti-MRSA therapy vs standard empirical antibiotic regimens. Retrospective multicenter cohort study was conducted of all hospitalizations in which patients received either anti-MRSA or standard therapy for community-onset pneumonia in the Veterans Health Administration health care system from January 1, 2008, to December 31, 2013. Subgroups of patients analyzed were those with initial intensive care unit admission, MRSA risk factors, positive results of a MRSA surveillance test, and positive results of a MRSA admission culture. Primary analysis was an inverse probability of treatment-weighted propensity score analysis using generalized estimating equation regression; secondary analyses included an instrumental variable analysis. Statistical analysis was conducted from June 14 to November 20, 2019. Empirical anti-MRSA therapy plus standard pneumonia therapy vs standard therapy alone within the first day of hospitalization. Risk of 30-day all-cause mortality after adjustment for patient comorbidities, vital signs, and laboratory results. Secondary outcomes included the development of kidney injury and secondary infections with Clostridioides difficile, vancomycin-resistant Enterococcus species, or gram-negative bacilli. Among 88 605 hospitalized patients (86 851 men; median age, 70 years [interquartile range, 62-81 years]), empirical anti-MRSA therapy was administered to 33 632 (38%); 8929 patients (10%) died within 30 days. Compared with standard therapy alone, in weighted propensity score analysis, empirical anti-MRSA therapy plus standard therapy was significantly associated with an increased adjusted risk of death (adjusted risk ratio [aRR], 1.4 [95% CI, 1.3-1.5]), kidney injury (aRR, 1.4 [95% CI, 1.3-1.5]), and secondary C difficile infections (aRR, 1.6 [95% CI, 1.3-1.9]), vancomycin-resistant Enterococcus spp infections (aRR, 1.6 [95% CI, 1.0-2.3]), and secondary gram-negative rod infections (aRR, 1.5 [95% CI, 1.2-1.8]). Similar associations between anti-MRSA therapy use and 30-day mortality were found by instrumental variable analysis (aRR, 1.6 [95% CI, 1.4-1.9]) and among patients admitted to the intensive care unit (aRR, 1.3 [95% CI, 1.2-1.5]), those with a high risk for MRSA (aRR, 1.2 [95% CI, 1.1-1.4]), and those with MRSA detected on surveillance testing (aRR, 1.6 [95% CI, 1.3-1.9]). No significant favorable association was found between empirical anti-MRSA therapy and death among patients with MRSA detected on culture (aRR, 1.1 [95% CI, 0.8-1.4]). This study suggests that empirical anti-MRSA therapy was not associated with reduced mortality for any group of patients hospitalized for pneumonia. These results contribute to a growing body of evidence that questions the value of empirical use of anti-MRSA therapy using existing risk approaches.

Abstract P2-16-36: Survival benefit of neoadjuvant chemotherapy versus adjuvant chemotherapy in HER2-positive early breast cancer: A propensity score-weighted analysis

Abstract INTRODUCTION: Neoadjuvant chemotherapy (NAC) is increasingly being used for locally advanced breast cancers (BCs) or aggressive BC tumors. However, no survival benefit of the neoadjuvant approach over receiving chemotherapy in the adjuvant setting has been proven so far in HER2-positive early breast cancer (BC) patients. The objective of this study was to compare the prognosis of patients with an HER2-positive BC treated with NAC to patients treated with adjuvant chemotherapy (AC). MATERIALS AND METHODS: We retrospectively identified in our institutional database 203 patients with HER2-positive BCs treated with NAC plus trastuzumab and 701 patients treated with adjuvant chemotherapy. As the treatment was not randomly allocated, we used a propensity score with an Inverse probability of received treatment weighting (IPTW) to generate a pseudo-population in which each covariate combination was balanced between treatment groups. The disease free (DFS), distant metastasis free (DMFS) and overall survival (OS) were evaluated using a weighted Cox model. The interactions with poor prognosis factors (initial tumour size, tumour grade, hormone receptor status and initial clinical nodal status) were tested to evaluate the effect of the NAC in high-risk tumours. RESULTS: By construction, patients, tumor characteristics and trastuzumab use were similar between the population treated with NAC and the population treated with adjuvant CT. No difference was found regarding DFS (p=0.3) neither DMFS (p=0.4) in the global population. However, there was a significant interaction effect between the strategy and the initial clinical nodal status, with a DFS benefit of NAC over AC in the node-positive group (HR 0.53 CI95% [0.31- 0.89]), as well as for DMFS (HR 0.39 95%CI [0.20-0.77]). We found a significant benefit in OS with the neoadjuvant strategy when compared with the adjuvant strategy (HR = 0.12 95%CI [0.03-0.47], p=0.002) and this difference was significant irrespective of tumour size, initial clinical nodal status and hormone receptor status. CONCLUSION: In patients with HER2-positive BCs, receiving NAC is associated with an improved OS when compared with chemotherapy received in the adjuvant setting. Our results support the fact that NAC should become a standard of care in HER2-positive tumours. Citation Format: Enora Laas, Arnaud Bresset, Jean Guillaume Feron, Jean-Yves Pierga, Florence Coussy, Audrey Bellesoeur, Beatriz Grandal, Eléonore De Guillebon, Sonia Rozette, Clemence Evrevin, Thomas Gaillard, Marick Lae, Anne Sophie Hamy, Fabien Reyal. Survival benefit of neoadjuvant chemotherapy versus adjuvant chemotherapy in HER2-positive early breast cancer: A propensity score-weighted analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-36.

Assessment of Out-of-Pocket Costs for Robotic Cancer Surgery in US Adults

Expensive technologies-including robotic surgery-experience rapid adoption without evidence of superior outcomes. Although previous studies have examined perioperative outcomes and costs, differences in out-of-pocket costs for patients undergoing robotic surgery are not well understood. To assess out-of-pocket costs and total payments for 5 types of common oncologic procedures that can be performed using an open or robotic approach. A retrospective, cross-sectional, propensity score-weighted analysis was performed using deidentified insurance claims for 1.9 million enrollees from the MarketScan database from January 1, 2012, to December 31, 2017. The final study sample comprised 15 893 US adults aged 18 to 64 years who were enrolled in an employer-sponsored health plan. Patients underwent either an open or robotic radical prostatectomy, hysterectomy, partial colectomy, radical nephrectomy, or partial nephrectomy for a solid-organ malignant neoplasm. Statistical analysis was performed from December 18, 2018, to June 5, 2019. Type of surgical procedure-robotic vs open. The primary outcome of interest was out-of-pocket costs associated with robotic and open surgery. The secondary outcome of interest was associated total payments. Among 15 893 patients (11 102 men; mean [SD] age, 55.4 [6.6] years), 8260 underwent robotic and 7633 underwent open procedures; patients undergoing robotic hysterectomy were older than those undergoing open hysterectomy (mean [SD] age, 55.7 [6.7] vs 54.6 [7.2] years), and patients undergoing open radical nephrectomy had more comorbidities than those undergoing robotic radical nephrectomy (≥2 comorbidities, 658 of 861 [76.4%] vs 244 of 347 [70.3%]). After adjustment for baseline characteristics, the robotic approach was associated with lower out-of-pocket costs for all procedures: -$137.75 (95% CI, -$240.24 to -$38.63) for radical prostatectomy (P = .006); -$640.63 (95% CI, -$933.62 to -$368.79) for hysterectomy (P < .001); -$1140.54 (95% CI, -$1397.79 to -$896.54) for partial colectomy (P < .001); -$728.32 (95% CI, -$1126.90 to -$366.08) for radical nephrectomy (P < .001); and -$302.74 (95% CI, -$523.14 to -$97.10) for partial nephrectomy (P = .003). The robotic approach was similarly associated with lower adjusted total payments: -$3872.62 (95% CI, -$5385.49 to -$2399.04) for radical prostatectomy (P < .001); -$29 640.69 (95% CI, -$36 243.82 to -$23 465.94) for hysterectomy (P < .001); -$38 151.74 (95% CI, -$46 386.16 to -$30 346.22) for partial colectomy; (P < .001); -$33 394.15 (95% CI, -$42 603.03 to -$24 955.20) for radical nephrectomy (P < .001); and -$9162.52 (95% CI, -$12 728.33 to -$5781.99) for partial nephrectomy (P < .001). This study found significant variation in perioperative costs according to surgical technique for both patients (out-of-pocket costs) and payers (total payments); the robotic approach was associated with lower out-of-pocket costs for all studied oncologic procedures.

Is Piperacillin-Tazobactam Effective for the Treatment of Pyelonephritis Caused by Extended-Spectrum β-Lactamase-Producing Organisms?

Limited data exist regarding the efficacy of piperacillin-tazobactam (TZP) for the management of nonbacteremic pyelonephritis caused by extended-spectrum β-lactamase (ESBL)-producing organisms. We conducted a multicenter observational study comparing clinical outcomes of adults hospitalized with ESBL-producing pyelonephritis who were receiving TZP versus carbapenems, using an inverse probability of treatment weighted propensity score analysis. Patients were eligible for inclusion if all of the following criteria were met: (1) urine cultures growing Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis at ≥50 000 colony-forming units/mL; (2) identification of an ESBL gene; (3) pyuria (≥10 white blood cells per high powered field in the urine); and (4) dysuria and fever plus at least 1 of the following symptoms: emesis, rigors, hypotension, or flank pain. There were 186 patients included in the propensity score-weighted cohort; 45 (24%) received TZP and 141 (76%) received a carbapenem. Of these 186 patients, 27% were admitted to the intensive care unit, 48% were immunocompromised, and 45% had underlying urologic abnormalities. There were no differences between the 2 groups in the proportion of patients (20% vs 25%) with recurrent cystitis or pyelonephritis with the same ESBL-producing organism within 30 days (odds ratio, 0.75; 95% confidence interval, .31-1.81; P = .52). There were no differences in the resolution of clinical symptoms by Day 7 or in 30-day mortality. There was 1 (2%) patient in the TZP arm and 11 (8%) patients in the carbapenem arm who had incident carbapenem-resistant organisms isolated within 30 days (P = .09). TZP may be a reasonable alternative to carbapenems for the management of ESBL-producing pyelonephritis and may mitigate the risk of emergence of carbapenem-resistant organisms, compared with carbapenem therapy.

Proceedings to the 6th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA): 14-16 October 2019, Hosted by Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL, USA.

Proceedings to the 6th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA): 14-16 October 2019, Hosted by Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL, USA.

Prognostic impact of pelvic and para-aortic lymphadenectomy on clinically-apparent stage I primary mucinous epithelial ovarian carcinoma: a multi-institutional study with propensity score-weighted analysis.

The exact impact of full-staging lymphadenectomy on patients with primary mucinous epithelial ovarian carcinoma confined to the ovary is still unclear. In this study, we investigated the prognostic impact of lymphadenectomy covering both pelvic and para-aortic lymph nodes in patients with clinically-apparent stage I mucinous epithelial ovarian carcinoma, using data from multi-institutions under a central pathological review system and analyses with a propensity score-based method. We conducted a regional multi-institutional retrospective study between 1986 and 2017. Among 4730 patients with malignant ovarian tumors, a total of 186 women with mucinous epithelial ovarian carcinoma were eligible. We evaluated differences in survival outcomes between patients with both pelvic and para-aortic lymphadenectomy and those with only pelvic lymphadenectomy and/or clinical lymph node evaluation. To analyze the therapeutic effects, the baseline imbalance between patients with both pelvic and para-aortic lymphadenectomy and others was adjusted with an inverse probability of treatment weighting using propensity score involving independent clinical variables. Fifty-five patients received both pelvic and para-aortic lymphadenectomy. With PS-based adjustment, both pelvic and para-aortic lymphadenectomy did not have additive effects regarding overall survival (P=0.696) and recurrence-free survival (P=0.978). Multivariate analysis similarly showed no significant impact of both pelvic and para-aortic lymphadenectomy on their prognosis. The effect of pelvic and para-aortic lymphadenectomy is limited for clinically-apparent stage I primary mucinous epithelial ovarian carcinoma as long as full peritoneal and clinical lymph node evaluations are conducted. The results of this study should be used as the basis for additional studies, including prospective trials.

Comparative Effectiveness of Radiofrequency Ablation, Surgical Resection and Transplantation for Early Hepatocellular Carcinoma by Cancer Risk Groups: Results of Propensity Score-Weighted Analysis.

PurposeControversies exist for which treatment is optimal for early hepatocellular carcinoma (HCC): radiofrequency ablation (RFA), surgical resection (SR), or transplantation (LT). We compared outcomes between treatments as first-line therapy for HCC patients measuring up to 5 cm or different cancer risk groups.Patients and methodsThe Surveillance, Epidemiology, and End Results database was retrieved for HCC patients treated with RFA, SR, or LT between 2004 and 2015. The effects of three treatments were compared using propensity score, inverse probability of treatment weights adjustment, and instrumental variable analysis for overall survival (OS) and competing risks regression models for disease-specific survival (DSS). We also evaluated whether the effect of treatments varied according to baseline clinical characteristics by locally weighted regression method.ResultsOf 7664 patients, RFA and SR yielded worse OS (HR 1.67, CI 1.43–1.70, P<0.001; HR 1.43, CI 1.40–1.67, P<0.001) and DSS (HR 2.00, CI 1.10–3.30, P<0.011; HR 2.50, CI 2.00–3.30, P<0.001) than LT. In patients with small tumors, SR may confer more survival benefits than RFA (HR>1) for different tumor sizes measuring up to 5 cm and may be an appropriate first-line treatment. Additionally, RFA has more survival benefits compared with SR (HR 0.83, CI 0.53–1.25) for those patients with low tumor risk and good general health condition (without any prognostic risk factors). However, those patients with a predicted 5-year overall mortality risk >30% seem to benefit more for SR than RFA.ConclusionDue to a shortage of donors, RFA and SR can be applied as either primary management of HCC or as a bridging therapy for LT. Furthermore, SR is an effective option for patients with different HCC tumor size. However, RFA could achieve comparable survival benefits with SR for patients without any risk factors.

Comparative outcomes of robot-assisted minimally invasive versus open esophagectomy in patients with esophageal squamous cell carcinoma: a propensity score-weighted analysis.

Robots are increasingly used in minimally invasive surgery. We evaluated the clinical benefits of robot-assisted minimally invasive esophagectomy (RAMIE) in comparison with the conventional open esophageal surgery. From 2012 to 2016, 371 patients with esophageal squamous cell carcinoma underwent an Ivor Lewis or McKeown procedure at our institution. Of these, 130 patients underwent laparoscopic gastric conduit formation followed by RAMIE, whereas 241 patients underwent conventional esophageal surgery, including laparotomy and open esophagectomy (OE). We compared the short- and long-term clinical outcomes of these patients using the propensity score-based inverse probability of treatment weighting technique (IPTW). Among the early outcomes, the OE group showed a higher incidence of pneumonia (P = 0.035) and a higher requirement for vasopressors (P = 0.001). Regarding the long-term outcomes, all-cause mortality was significantly higher (P = 0.001) and disease-free survival was lower (P = 0.006) in the OE group. Wound-related problems also occurred more frequently in the OE group (P = 0.020) during the long-term follow-up. There was no statistical intergroup difference in the recurrence rates (P = 0.191). The Cox proportional-hazard analysis demonstrated that wound problems (HR 0.16, 95% CI 0.02-0.57; P = 0.017), pneumonia (HR 0.23, 95% CI 0.06-0.68; P = 0.019), and use of vasopressors (HR 0.14, 95% CI 0.08-0.25; P = 0.001) were independent predictors of mortality. RAMIE could be a better surgical option for selected patients with esophageal squamous cell carcinoma.

Unexpected high-risk pathologic features following thyroidectomy in the chinese immigrant population.

To compare rates of unexpected high-risk pathologic features between Chinese and non-Asian patients who underwent thyroidectomy for papillary thyroid cancer. This was a retrospective cohort study at a tertiary academic urban medical center. Patients who underwent thyroidectomy for papillary carcinoma from 2015 to 2017 were included. Patient demographics, tumor characteristics, and tumor histopathology were analyzed. Primary outcome was the presence of adverse histopathologic features such as lymphovascular invasion (LVI) or microscopic/minimal extrathyroidal extension (mETE). Differences between the groups were analyzed using multivariate logistical regression analysis and propensity score-weighted analysis. One hundred seventy-nine patients were included: 58 Chinese-born and 121 non-Asian. The median age of the cohort was 47 years old (36-58). Twenty-nine percent of patients were male, and 71% were female. There was no statistically significant difference between the two cohorts in rates of LVI, multifocality, extent of surgery, or presence of thyroiditis. Patients with mETE were more likely to have larger tumors (P = 0.00247). Both the multivariate and propensity-weighted models demonstrated that Chinese ancestry was independently associated with an increased rate of unexpected mETE (adjusted prevalence ratio, 2.52; 95% confidence interval, 1.82-3.48). mETE is significantly higher in the immigrant Chinese compared to the non-Asian population. Given the high prevalence of unexpected mETE in the Chinese population, the added risk of this finding should be brought into the discussion during initial surgical planning. 3 Laryngoscope, 130:1844-1849, 2020.

Effects of preoperative oral management by dentists on postoperative outcomes following esophagectomy: Multilevel propensity score matching and weighting analyses using the Japanese inpatient database: Erratum.

Effects of preoperative oral management by dentists on postoperative outcomes following esophagectomy: Multilevel propensity score matching and weighting analyses using the Japanese inpatient database: Erratum.

Chemoradiation Vs Radical Cystectomy for Muscle-invasive Bladder Cancer: A Propensity Score-weighted Comparative Analysis Using the National Cancer Database

To address the overarching question whether chemoradiation therapy (CMT) offers overall survival (OS) similar to that of radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC), we performed analyses using the National Cancer Database. Patients diagnosed with MIBC in 2004-2014 who underwent RC or received primary CMT were identified in the National Cancer Database. Survival was estimated using the weighted Kaplan-Meier method, and propensity score-weighted Cox proportional hazards model were used to evaluate association of clinicopathologic features with outcome. Of 484,367 patients with a diagnosis of bladder cancer, 35,856 underwent RC and 4050 received CMT. After applying the exclusion/inclusion criteria, data for 15,854 patients who underwent RC and 2083 who received CMT were available for analysis. Five-year OS was 40.4% in the RC group and 29.4% in the CMT group (P <.001). OS was significantly shorter in the CMT group than in the RC group in both multivariate analysis (hazards ratio [HR] 1.15, 95% CI 1.08-1.22; P <.001) and propensity score-weighted analysis (HR 1.18, 95% CI 1.07-1.30; P <.001). Interaction terms indicated better survival after RC in patients younger than 70 years (HR 1.61, 95% CI 1.34-1.93; P <.001); subgroup analyses identified a survival benefit in patients with N0/N1 disease who underwent RC (HR 1.21, 95% CI 1.09-1.33; P <.001). OS after 1 year of treatment was increased in RC group compared to CMT group in patient with MIBC. Further studies are required to identify optimal treatment for specific patients.

Sequencing of therapy in women with stage III endometrial carcinoma receiving adjuvant combination chemotherapy and radiation

ObjectiveWhile women with stage III endometrial cancer are often treated with chemotherapy and external beam radiation, the optimal sequence of these modalities is unknown. We examined the association between the sequence of chemotherapy (CT) and external beam radiation therapy (RT) on survival for women with stage IIIC endometrial carcinoma. MethodsThe National Cancer Database was used to identify women with stage IIIC endometrial carcinoma treated with adjuvant CT and RT from 2004 to 2015. Patients were stratified based on the sequence of therapy: RT before CT, CT before RT, or concurrent therapy. The association between treatment sequence and mortality was examined through a weighted propensity score analysis. ResultsA total of 6981 patients were identified, including 5116 (73.3%) who received CT before RT, 696 (10.0%) who received RT before CT, and 1169 (16.7%) who received concurrent therapy. The use of CT-RT increased from 39.9% in 2004 to 75.5% in 2015, while use of RT-CT decreased from 34.0% to 4.4% and concurrent therapy decreased from 26.1% to 20.2% over the same period (P < 0.001). Compared to CT-RT, there was no difference in risk of mortality with RT before CT (HR = 1.01; 95% CI, 0.86–1.19) while concurrent therapy was associated with a 47% increased risk of mortality (HR = 1.47; 95% CI, 1.31–1.66). In a sensitivity analysis combining the groups that received RT first (RT before CT or concurrent RT-CT), mortality was 25% higher (HR = 1.25; 95% CI, 1.13–1.39) compared to a strategy of CT followed by RT. ConclusionAmong women with stage IIIC endometrial carcinoma treated with combination chemotherapy and external beam radiation, a strategy employing chemotherapy first is associated with improved survival compared to concurrent therapy.

Outcomes of Lymph Node Dissection for Non-metastatic Pancreatic Neuroendocrine Tumors: A Propensity Score-Weighted Analysis of the National Cancer Database.

Although the National Comprehensive Cancer Network (NCCN) guidelines recommend use of lymph node dissection (LND) in patients with pancreatic neuroendocrine tumors (pNETs) > 2cm, there is limited evidence to support the association between use of LND and overall survival (OS). Patients with resected pNETs were identified in the National Cancer Database (2004-2014). The inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. IPTW-adjusted Kaplan-Meier curves and Cox proportional hazards models were used to compare OS of patients in different treatment groups. A total of 2664 patients diagnosed met the study entry criteria. Of these, 2132 patients (80.6%) received LND, with a median of nine nodes removed. Positive nodes were identified in 28.0% of patients who underwent LND. IPTW-adjusted Kaplan-Meier analysis showed that median OS was similar between the LND and LND-omitted groups (152.8 vs. 147.3months; p = 0.61). In IPTW-adjusted Cox proportional hazards regression analysis, LND was not associated with an OS benefit (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.94-1.42; p = 0.18). The results were consistent across subgroups stratified by clinical T and N stages. Among patients with lymph node metastasis, the number of removed nodes (NRN) above the median was not associated with an improved OS (HR 0.82, 95% CI 0.60-1.13; p = 0.22). LND had no additional therapeutic benefit among patients undergoing resection for pNETs. The present findings should be considered when managing patients with resectable pNETs.

The impact of unplanned excisions of truncal/extremity soft tissue sarcomas: A multi-institutional propensity score analysis from the US Sarcoma Collaborative.

Our aim was to compare outcomes in patients who underwent unplanned excisions (UE) of soft-tissue sarcomas (STS) against patients with planned excisions (PE). The retrospective 7-institution US Sarcoma Collaborative database was used. Patients with curative-intent resection of truncal/extremity STS between 2000 and 2016 were included. Propensity score weighting analysis (PSWA) was performed. Endpoints were locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-specific survival (DSS). One thousand five hundred and ninety-six patients were included. Eighty-two percent (n = 1315) underwent PE and 18% (n = 281) underwent UE. Compared with PE, patients with UE were younger with smaller tumors with similar tumor grade. Unmatched analysis revealed PE was associated with worse DMFS (hazard ratio [HR] 1.95, P = .009) and DSS (HR 1.78, P = .039), but not LRFS compared with UE. On PSWA, UE had earlier LRFS (3-year LRFS: 80.5% vs 89.8%, P = .039), but not DMFS or DSS. By grade, patients with high-grade tumors and UE had worse LRFS (1-year LRFS: 90% vs 94%, P = .015), but similar DMFS and DSS compared with PE. In low-grade patients, UE and PE had similar LRFS, DMFS, or DSS. UE of STS is not associated with worse prognosis compared to PE, though UE is associated with earlier locoregional recurrence in patients with high-grade tumors. Multimodality therapy is needed to achieve improved outcomes in these patients.

Comparative effectiveness of proton therapy versus photon therapy as part of concurrent chemoradiotherapy for locally advanced cancer.

6521 Background: Concurrent chemo-radiotherapy is standard-of-care curative treatment for many cancers, but is associated with substantial morbidity. Proton therapy may increase the tolerability or effectiveness of concurrent chemo-radiotherapy by reducing radiation to normal tissues. Methods: We conducted a comparative effectiveness study of adult non-metastatic cancer patients treated with curative intent with proton chemo-radiotherapy vs. photon chemo-radiotherapy from 2011-2016 at the University of Pennsylvania. Re-irradiation and disease sites treated with photon-only therapy were excluded. Data on adverse events and survival was gathered prospectively. Primary endpoint was 90-day adverse events associated with unplanned hospitalizations (CTCAEv4 grade ≥3 adverse events). Secondary endpoints included decline in ECOG performance status during treatment, 90-day grade ≥2 adverse events, disease-free survival (DFS) and overall survival (OS). Modified Poisson regression models with inverse propensity score weighting were fit for both outcomes. Propensity scores were estimated using an ensemble machine-learning approach. Results: 1,483 patients were included (391 proton/1,092 photon). Proton patients were significantly older (median 66 vs. 61), had less favorable Charlson-Deyo comorbidity scores (median 3.0 vs. 2.0), and had lower integral radiation dose to tissues outside the target (p &lt; 0.05 for all). Baseline toxicity and performance status were similar (p &gt; 0.05). In propensity score weighted-analyses, proton chemo-radiotherapy was associated with significantly lower relative risk (RR) of 90-day grade ≥3 adverse events [11.5%(95%CI 8.3-14.7%) for protons; 27.6%(95%CI 24.9-30.2%) for photons; RR 0.31, 95%CI 0.15-0.66, p &lt; 0.01]; 90-day grade ≥2 adverse events (RR 0.78, 95%CI 0.65-0.93, p &lt; 0.01); and decline in performance status during treatment (RR 0.51, 95%CI 0.37-0.71, p &lt; 0.01). There was no difference in DFS or OS. Conclusions: In adults with locally advanced cancer, proton chemo-radiotherapy was associated with significantly reduced acute adverse events causing unplanned hospitalizations with similar disease-free and overall survival.

Midostaurin added to chemotherapy and continued single-agent maintenance therapy in acute myeloid leukemia with FLT3-ITD

AbstractPatients with acute myeloid leukemia (AML) and a FLT3 internal tandem duplication (ITD) have poor outcomes to current treatment. A phase 2 hypothesis-generating trial was conducted to determine whether the addition of the multitargeted kinase inhibitor midostaurin to intensive chemotherapy followed by allogeneic hematopoietic cell transplantation (alloHCT) and single-agent maintenance therapy of 12 months is feasible and favorably influences event-free survival (EFS) compared with historical controls. Patients 18 to 70 years of age with newly diagnosed AML and centrally confirmed FLT3-ITD were eligible: 284 patients were treated, including 198 younger (18-60 years) and 86 older (61-70 years) patients. Complete remission (CR) rate, including CR with incomplete hematological recovery (CRi) after induction therapy, was 76.4% (younger, 75.8%; older, 77.9%). The majority of patients in CR/CRi proceeded to alloHCT (72.4%). Maintenance therapy was started in 97 patients (34%): 75 after alloHCT and 22 after consolidation with high-dose cytarabine (HiDAC). Median time receiving maintenance therapy was 9 months after alloHCT and 10.5 months after HiDAC; premature termination was mainly a result of nonrelapse causes (gastrointestinal toxicity and infections). EFS and overall survival at 2 years were 39% (95% confidence interval [CI], 33%-47%) and 34% (95% CI, 24%-47%) and 53% (95% CI, 46%-61%) and 46% (95% CI, 35%-59%) in younger and older patients, respectively. EFS was evaluated in comparison with 415 historical controls treated within 5 prospective trials. Propensity score-weighted analysis revealed a significant improvement of EFS by midostaurin (hazard ratio [HR], 0.58; 95% CI, 0.48-0.70; P < .001) overall and in older patients (HR, 0.42; 95% CI, 0.29-0.61). The study was registered at www.clinicaltrials.gov as #NCT01477606.

Impact of Surgical Approach on Patient-Reported Outcomes after Radical Prostatectomy: A Propensity Score-Weighted Analysis from a Multicenter, Prospective, Observational Study (The Pros-IT CNR Study)

Background: To report health-related quality of life outcomes as assessed by validated patient-reported outcome measures (PROMs) after radical prostatectomy (RP). ­Methods: This study analyzed patients treated with RP within The PROState cancer monitoring in Italy, from the National Research Council (Pros-IT CNR). Italian versions of Short-Form Heath Survey and university of California los Angeles-prostate cancer index questionnaires were administered. PROMs were physical composite scores, mental composite scores and urinary, bowel, sexual functions and bothers (UF/B, BF/B, SF/B). Baseline unbalances were controlled with propensity scores and stabilized inverse weights; differences in PROMs between different RP approaches were estimated by mixed models. Results: Of 541 patients treated with RP, 115 (21%) received open RP (ORP), 90 (17%) laparoscopic RP (LRP) and 336 (61%) robot-assisted RP (RARP). At head-to-head ­comparisons, RARP showed higher 12-month UF vs. LRP (interaction treatment * time p = 0.03) and 6-month SF vs. ORP (p < 0.001). At 12-month from surgery, 67, 73 and 79% of patients used no pad for urinary loss in ORP, LRP and RARP respectively (no differences for each comparison). Conversely, 16, 27 and 40% of patients declared erections firm enough for sexual intercourse in ORP, LRP and RARP respectively (only significant difference for ORP vs. RARP, p = 0.0004). Conclusions: Different RP approaches lead to significant variations in urinary and sexual PROMs, with a general trend in favour of RARP. However, their clinical significance seems limited.

Combination therapy with TACE + ablation versus TACE + SBRT for hepatocellular carcinoma (HCC): Comparative analysis with propensity score-weighted cohorts.

443 Background: To assess the relative efficacy and toxicity associated with TACE+Ablation (Ablation) or TACE+SBRT (SBRT) in a large cohort of patients with unresectable HCC. Methods: Patients with HCC undergoing Ablation or SBRT from 2006-2016 with available follow up were included. Treatment groups were different at baseline regarding tumor stage (BCLC A, B and C: 96%, 4%, 0% (Ablation) vs. 73%, 14% and 13% (SBRT), P &lt; 0.001) and severity of liver disease (CTP A, B, and C: 55%, 45% and 0% (Ablation) vs. 50%, 41%, and 9% (SBRT), P = 0.007). Propensity scores were calculated with age, sex, BCLC stage, CTP class, etiology of liver disease, tumor number, and diameter to balance the cohorts. Average treatment effects on survival with multivariable propensity score-weighted competing risk Cox regression models were evaluated, with BCLC stage, number of treated tumors and liver transplant as additionally controlled variables. Primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), local tumor control and hepatotoxicity. Treatment-related hepatotoxicity was defined as a two point change in CTP within six months after treatment. Results: 192 subjects were included (101 Ablation, 91 SBRT; median age=60 years, 75% men). Liver disease included HCV (78%), alcohol (35%) and NASH (8%). Liver transplant-adjusted 1- and 2-year OS rates were significantly greater for Ablation vs SBRT (88% vs. 75% and 77% vs. 50%, P&lt;0.001). 1-and 2-year PFS rates were significantly greater for Ablation vs. SBRT (84% vs. 65% and 75% vs. 51%, P &lt; 0.001). 1- and 2- year local tumor control rates were similar with both strategies (99% vs. 91% and 94% vs. 87%, P=0.298). Propensity score-weighted multivariable analysis showed significantly higher OS (sHR: 2.31, P = 0.006) and PFS rates (sHR:1.75, P = 0.008) with Ablation compared to SBRT. Ablation was also associated with lower post-treatment hepatotoxicity compared with SBRT (5% vs. 12%, P = 0.001). Conclusions: TACE+Ablation demonstrated higher OS/PFS and lower post-treatment hepatotoxicity compared with TACE+SBRT. Local disease control up to two years was equivocal, potentially suggesting equipoise for bridge to transplant.