SMAD4 loss predicts worse overall and distant metastasis-free survival in patients with resected pancreatic adenocarcinoma.

BACKGROUND: In select patients, pancreatic adenocarcinoma remains a local disease, yet there are no validated biomarkers to predict this behavior and who may benefit from aggressive local treatments. This study sought to determine if SMAD4 (mothers against decapentaplegic homolog 4) messenger RNA-sequencing (RNA-seq) expression is a robust method for predicting overall survival (OS) and distant metastasis-free survival (DMFS) in patients with resected pancreatic adenocarcinoma. METHODS: Utilizing The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), 322 patients with resected stage I-III pancreatic adenocarcinoma were identified. In TCGA, multivariable proportional hazards models were used to determine the association of SMAD4 genomic aberrations and RNA-seq expression with OS and DMFS. In the ICGC, analysis sought to confirm the predictive performance of RNA-seq via multivariable models and receiver operator characteristic curves. RESULTS: In TCGA, the presence of SMAD4 genomic aberrations was associated with worse OS (hazard ratio [HR], 1.55; 95% CI, 1.00-2.40; p = .048) but not DMFS (HR, 1.33; 95% CI, .87-2.03; p = .19). Low SMAD4 RNA-seq expression was associated with worse OS (HR, 1.83; 95% CI, 1.17-2.86; p = .008) and DMFS (HR, 1.70; 95% CI, 1.14-2.54; p = .009). In the ICGC, increased SMAD4 RNA-seq expression correlated with improved OS (area under the curve [AUC], .92; 95% CI, .86-.94) and DMFS (AUC, .84; 95% CI, .82-.87). CONCLUSIONS: In patients with resected pancreatic adenocarcinoma, SMAD4 genomic aberrations are associated with worse OS but do not predict for DMFS. Increased SMAD4 RNA-seq expression is associated with improved OS and DMFS in patients with resected pancreatic adenocarcinoma. This reproducible finding suggests SMAD4 RNA-seq expression may be a useful marker to predict metastatic spread.

Logistical, technical, and radiation safety aspects of establishing a radiopharmaceutical therapy program: A case in Lutetium-177 prostate-specific membrane antigen (PSMA) therapy.

Prostate-specific membrane antigen (PSMA) is a cell surface protein highly expressed in nearly all prostate cancers, with restricted expression in some normal tissues. The differential expression of PSMA from tumor to non-tumor tissue has resulted in the investigation of numerous targeting strategies for therapy of patients with metastatic prostate cancer. In March of 2022, the FDA granted approval for the use of lutetium-177 PSMA-617 (Lu-177-PSMA-617) for patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. Therefore, the use of Lu-177-PSMA-617 is expected to increase and become more widespread. Herein, we describe logistical, technical, and radiation safety considerations for implementing a radiopharmaceutical therapy program, with particular focus on the development of operating procedures for therapeutic administrations. Major steps for a center in the U.S. to implement a new radiopharmaceutical therapy (RPT) program are listed below, and then demonstrated in greater detail via examples for Lu-177-PSMA-617 therapy.

Survival Outcomes in Men with Unfavorable Intermediate-Risk and High-Risk Prostate Cancer Treated with Prostate-Only versus Whole Pelvic Radiation Therapy.

PURPOSE: Men with unfavorable intermediate-risk (UIR-PCa) or high-risk prostate cancer (HR-PCa) are often treated with definitive external beam radiotherapy (EBRT) plus androgen deprivation therapy. Treatment is frequently intensified by electively treating the pelvic lymph nodes (LNs) with whole pelvis radiotherapy (WPRT), but practice patterns and the benefits of WPRT are not well defined. We hypothesized that men treated with WPRT would have improved overall survival (OS) relative to men treated with prostate-only radiotherapy. MATERIALS AND METHODS: National Cancer Database records of men diagnosed between 2008-2015 with UIR-PCa or HR-PCa and treated with prostate EBRT±androgen deprivation therapy (72-86.4 Gy) with (15,175) or without (13,549) WPRT were reviewed. Risk of LN involvement was calculated using the Memorial Sloan Kettering Cancer Center nomogram. Measured confounders were balanced with inverse probability of treatment weighting and OS hazard ratios (HRs) were generated using multivariable Cox regression. RESULTS: Of the men, 53% received WPRT. Every 1% increase in risk of LN involvement correlated with a 1% increase in risk of death (p <0.001). WPRT trended toward improved OS in all men with UIR-PCa and HR-PCa (HR: 0.95 [95% CI: 0.90-1.006], p=0.055). WPRT correlated with improved OS in men with Gleason 9 and 10 disease (HR: 0.87 [0.78-0.98], p=0.02) or risk of LN involvement ≥10% (HR: 0.93 [0.87-0.99], p=0.03). CONCLUSIONS: Men with higher LN risk scores and Gleason grade benefited from WPRT. These results complement the recent POP-RT randomized trial in mostly positron emission tomography/computerized tomography-staged patients, demonstrating that a more heterogeneous population of men staged without functional imaging benefits from WPRT.

Outcomes of Patients With Unfavorable Intermediate-Risk Prostate Cancer Treated With External-Beam Radiotherapy Versus Brachytherapy Alone.

BACKGROUND: The NCCN Guidelines for Prostate Cancer currently recommend several definitive radiotherapy (RT) options for men with unfavorable intermediate-risk (UIR) prostate cancer: external-beam RT (EBRT) plus androgen deprivation therapy (ADT) or EBRT plus brachytherapy boost with or without ADT. However, brachytherapy alone with or without ADT is not well defined and is currently not recommended for UIR prostate cancer. We hypothesized that men treated with brachytherapy with or without ADT have comparable survival rates to men treated with EBRT with or without ADT. METHODS: A total of 31,783 men diagnosed between 2004 and 2015 with UIR prostate cancer were retrospectively reviewed from the National Cancer Database. Men were stratified into 4 groups: EBRT (n=12,985), EBRT plus ADT (n=12,960), brachytherapy (n=4,535), or brachytherapy plus ADT (n=1,303). Inverse probability of treatment weighting (IPTW) was used to adjust for covariable imbalances, and weight-adjusted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) hazard ratios (HRs). RESULTS: Relative to EBRT alone, the following treatments were associated with improved OS: EBRT plus ADT (HR, 0.92; 95% CI, 0.87-0.97; P=.002), brachytherapy alone (HR, 0.90; 95% CI, 0.83-0.98; P=.01), and brachytherapy plus ADT (HR, 0.78; 95% CI, 0.69-0.88; P=.00006). Brachytherapy correlated with improved OS relative to EBRT in men who were not treated with ADT (HR, 0.92; 95% CI, 0.84-0.99; P=.03) and in those receiving ADT (HR, 0.84; 95% CI, 0.75-0.95; P=.004). At 10-year follow-up, 56% and 63% of men receiving EBRT and brachytherapy, respectively, were alive (P<.0001). IPTW was used to determine the average treatment effect of definitive brachytherapy. Relative to EBRT, definitive brachytherapy correlated with improved OS (HR, 0.90; 95% CI, 0.84-0.97; P=.009) on weight-adjusted MVA. CONCLUSIONS: Definitive brachytherapy was associated with improved OS compared with EBRT. The addition of ADT to both EBRT and definitive brachytherapy was associated with improved OS. These results suggest that definitive brachytherapy should be considered as an option for men with UIR prostate cancer.

Correction: Urine tumor DNA detection of minimal residual disease in muscle-invasive bladder cancer treated with curative-intent radical cystectomy: A cohort study.

[This corrects the article DOI: 10.1371/journal.pmed.1003732.].

Urine tumor DNA detection of minimal residual disease in muscle-invasive bladder cancer treated with curative-intent radical cystectomy: A cohort study.

BACKGROUND: The standard of care treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy, which is typically preceded by neoadjuvant chemotherapy. However, the inability to assess minimal residual disease (MRD) noninvasively limits our ability to offer bladder-sparing treatment. Here, we sought to develop a liquid biopsy solution via urine tumor DNA (utDNA) analysis. METHODS AND FINDINGS: We applied urine Cancer Personalized Profiling by Deep Sequencing (uCAPP-Seq), a targeted next-generation sequencing (NGS) method for detecting utDNA, to urine cell-free DNA (cfDNA) samples acquired between April 2019 and November 2020 on the day of curative-intent radical cystectomy from 42 patients with localized bladder cancer. The average age of patients was 69 years (range: 50 to 86), of whom 76% (32/42) were male, 64% (27/42) were smokers, and 76% (32/42) had a confirmed diagnosis of MIBC. Among MIBC patients, 59% (19/32) received neoadjuvant chemotherapy. utDNA variant calling was performed noninvasively without prior sequencing of tumor tissue. The overall utDNA level for each patient was represented by the non-silent mutation with the highest variant allele fraction after removing germline variants. Urine was similarly analyzed from 15 healthy adults. utDNA analysis revealed a median utDNA level of 0% in healthy adults and 2.4% in bladder cancer patients. When patients were classified as those who had residual disease detected in their surgical sample (n = 16) compared to those who achieved a pathologic complete response (pCR; n = 26), median utDNA levels were 4.3% vs. 0%, respectively (p = 0.002). Using an optimal utDNA threshold to define MRD detection, positive utDNA MRD detection was highly correlated with the absence of pCR (p < 0.001) with a sensitivity of 81% and specificity of 81%. Leave-one-out cross-validation applied to the prediction of pathologic response based on utDNA MRD detection in our cohort yielded a highly significant accuracy of 81% (p = 0.007). Moreover, utDNA MRD-positive patients exhibited significantly worse progression-free survival (PFS; HR = 7.4; 95% CI: 1.4-38.9; p = 0.02) compared to utDNA MRD-negative patients. Concordance between urine- and tumor-derived mutations, determined in 5 MIBC patients, was 85%. Tumor mutational burden (TMB) in utDNA MRD-positive patients was inferred from the number of non-silent mutations detected in urine cfDNA by applying a linear relationship derived from The Cancer Genome Atlas (TCGA) whole exome sequencing of 409 MIBC tumors. We suggest that about 58% of these patients with high inferred TMB might have been candidates for treatment with early immune checkpoint blockade. Study limitations included an analysis restricted only to single-nucleotide variants (SNVs), survival differences diminished by surgery, and a low number of DNA damage response (DRR) mutations detected after neoadjuvant chemotherapy at the MRD time point. CONCLUSIONS: utDNA MRD detection prior to curative-intent radical cystectomy for bladder cancer correlated significantly with pathologic response, which may help select patients for bladder-sparing treatment. utDNA MRD detection also correlated significantly with PFS. Furthermore, utDNA can be used to noninvasively infer TMB, which could facilitate personalized immunotherapy for bladder cancer in the future.

Compliance with sentinel lymph node biopsy guidelines for invasive melanomas treated with Mohs micrographic surgery.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has not been studied for invasive melanomas treated with Mohs micrographic surgery using frozen-section MART-1 immunohistochemical stains (MMS-IHC). The primary objective of this study was to assess the accuracy and compliance with National Comprehensive Cancer Network (NCCN) guidelines for SLNB in a cohort of patients who had invasive melanoma treated with MMS-IHC. METHODS: This retrospective cohort study included all patients who had primary, invasive, cutaneous melanomas treated with MMS-IHC at a single academic center between March 2006 and April 2018. The primary outcomes were the rates of documenting discussion and performing SLNB in patients who were eligible based on NCCN guidelines. Secondary outcomes were the rate of identifying the sentinel lymph node and the percentage of positive lymph nodes. RESULTS: In total, 667 primary, invasive, cutaneous melanomas (American Joint Committee on Cancer T1a-T4b) were treated with MMS-IHC. The median patient age was 69 years (range, 25-101 years). Ninety-two percent of tumors were located on specialty sites (head and/or neck, hands and/or feet, pretibial leg). Discussion of SLNB was documented for 162 of 176 (92%) SLNB-eligible patients, including 127 of 127 (100%) who had melanomas with a Breslow depth >1 mm. SLNB was performed in 109 of 176 (62%) SLNB-eligible patients, including 102 of 158 melanomas (65%) that met NCCN criteria to discuss and offer SLNB and 7 of 18 melanomas (39%) that met criteria to discuss and consider SLNB. The sentinel lymph node was successfully identified in 98 of 109 patients (90%) and was positive in 6 of those 98 patients (6%). CONCLUSIONS: Combining SLNB and MMS-IHC allows full pathologic staging and confirmation of clear microscopic margins before reconstruction of specialty site invasive melanomas. SLNB can be performed accurately and in compliance with consensus guidelines in patients with melanoma using MMS-IHC.

Cardiovascular Events in Men with Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS).

PURPOSE: The comparative cardiovascular risk profiles of available hormone therapies for the treatment of prostate cancer is not known. MATERIALS AND METHODS: We queried the U.S. Food and Drug Administration Adverse Event Reporting System, a retrospective, pharmacovigilance database, for cardiovascular adverse event reports in men with prostate cancer receiving gonadotropin releasing hormone (GnRH) agonists, GnRH antagonists, androgen receptor antagonists, and/or androgen synthesis inhibitors from January 2000 to April 2020. RESULTS: Cardiovascular adverse events accounted for 6,231 reports (12.6%) on hormone monotherapy and 1,793 reports (26.1%) on combination therapy. Arterial vascular events were reported most commonly, followed by arrhythmias, heart failure, and venous thromboembolism. Compared to GnRH agonists, GnRH antagonists were associated with fewer cardiovascular adverse event reports as monotherapy (adjusted reporting odds ratio [ROR]=0.70 [95% CI 0.59-0.84], p <0.001) and as combination therapy (ROR=0.47 [0.34-0.67], p <0.0001), driven by reductions in arterial vascular events. Second generation androgen receptor antagonists and abiraterone were associated with more reports of hypertension requiring hospitalization (ROR=1.21 [1.03-1.41], p=0.02 and ROR=1.19 [1.01-1.40], p=0.03, respectively), and more heart failure events when used in combination with GnRH antagonists (ROR=2.79 [1.30-6.01], p=0.009 and ROR=2.57 [1.12-5.86], p=0.03). CONCLUSIONS: In this retrospective analysis of a pharmacovigilance database, arterial vascular events were the most commonly reported cardiovascular adverse events in men on hormone therapy for prostate cancer. GnRH antagonists were associated with fewer reports of overall cardiovascular events and arterial vascular events than GnRH agonists. Additional study is needed to identify optimal strategies to reduce cardiovascular morbidity among men with prostate cancer receiving hormone therapy.

Reduced Wide Local Excision Margins are Associated with Increased Risk of Relapse and Death from Merkel Cell Carcinoma.

INTRODUCTION: Current recommendations regarding the size of wide local excision (WLE) margins for Merkel cell carcinoma (MCC) are not well established. METHODS: WLE and pathologic margins were respectively reviewed from 79 patients with stage I or II MCC, who underwent WLE at Washington University in St Louis from 2005 to 2019. Outcomes included local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant recurrence-free survival (DRFS), disease-free survival (DFS), and disease-specific survival (DSS). RESULTS: Thirty-two percent of patients received adjuvant radiotherapy (aRT). At 1 year, DFS was 51.3%, 71.4%, and 87.8% for patients with WLE margins < 1 cm, 1-1.9 cm, and ≥ 2 cm, respectively (p = 0.02). At 3 years, the DSS was 57.7%, 82.6%, and 100% for patients with WLE margins < 1 cm, 1-1.9 cm, and ≥ 2 cm, respectively (p = 0.02). Multivariable Cox analysis demonstrated that every 1-cm increase in WLE margins was associated with improved RRFS [hazard ratio (HR) = 0.28, 95% confidence interval (CI): 0.11-0.75], DRFS (HR 0.30, CI 0.08-0.99), DFS (HR 0.42, CI 0.21-0.86), and DSS (HR 0.16, CI 0.04-0.61). WLE and pathologic margin size were moderately-to-strongly correlated (r = 0.66). Close or positive pathologic margins (< 3 mm) were associated with reduced DRFS (HR 6.83, CI 1.80-25.9), DFS (HR 2.98, CI 1.31-6.75), and DSS (HR 3.52, CI 1.14-10.9). CONCLUSION: Reduced WLE and pathologic margins were associated with higher risk of relapse and death from MCC. Larger WLE margins are important in populations with lower rates of adjuvant radiation.

NCCN Guidelines® Insights: Squamous Cell Skin Cancer, Version 1.2022.

The NCCN Guidelines for Squamous Cell Skin Cancer provide recommendations for diagnostic workup, clinical stage, and treatment options for patients with cutaneous squamous cell carcinoma. The NCCN panel meets annually to discuss updates to the guidelines based on comments from panel members and the Institutional Review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new surgical recommendation terminology (peripheral and deep en face margin assessment), as well as recent updates on topical prophylaxis, immunotherapy for regional and metastatic disease, and radiation therapy.

Management of primary skin cancer during a pandemic: Multidisciplinary recommendations.

During the coronavirus disease 2019 (COVID-19) pandemic, providers and patients must engage in shared decision making regarding the pros and cons of early versus delayed interventions for localized skin cancer. Patients at highest risk of COVID-19 complications are older; are immunosuppressed; and have diabetes, cancer, or cardiopulmonary disease, with multiple comorbidities associated with worse outcomes. Physicians must weigh the patient's risk of COVID-19 complications in the event of exposure against the risk of worse oncologic outcomes from delaying cancer therapy. Herein, the authors have summarized current data regarding the risk of COVID-19 complications and mortality based on age and comorbidities and have reviewed the literature assessing how treatment delays affect oncologic outcomes. They also have provided multidisciplinary recommendations regarding the timing of local therapy for early-stage skin cancers during this pandemic with input from experts at 11 different institutions. For patients with Merkel cell carcinoma, the authors recommend prioritizing treatment, but a short delay can be considered for patients with favorable T1 disease who are at higher risk of COVID-19 complications. For patients with melanoma, the authors recommend delaying the treatment of patients with T0 to T1 disease for 3 months if there is no macroscopic residual disease at the time of biopsy. Treatment of tumors ≥T2 can be delayed for 3 months if the biopsy margins are negative. For patients with cutaneous squamous cell carcinoma, those with Brigham and Women's Hospital T1 to T2a disease can have their treatment delayed for 2 to 3 months unless there is rapid growth, symptomatic lesions, or the patient is immunocompromised. The treatment of tumors ≥T2b should be prioritized, but a 1-month to 2-month delay is unlikely to worsen disease-specific mortality. For patients with squamous cell carcinoma in situ and basal cell carcinoma, treatment can be deferred for 3 months unless the individual is highly symptomatic.

Concurrent chemo-radiotherapy with proton therapy: reduced toxicity with comparable oncological outcomes vs photon chemo-radiotherapy.

Concurrent chemo-radiotherapy is a commonly employed curative treatment approach for locally advanced cancers but is associated with considerable morbidity. Chemo-radiotherapy using proton therapy may be able to reduce side effects of treatment and improve efficacy, but this remains an area of controversy and data are relatively limited. We comment on recently published studies and discuss future directions for proton therapy.

False-positive pregnancy test secondary to ectopic expression of human chorionic gonadotropin by a gastrointestinal stromal tumor.

Tumors can rarely overexpress human chorionic gonadotropin (hCG) resulting in false-positive pregnancy tests. Here, we report a 44-year-old female with a metastatic gastrointestinal stromal tumor (GIST) who presented with a positive urine pregnancy test before radiotherapy. Further workup ruled out pregnancy. Following radiotherapy, her metastatic disease progressed and her hCG level continued to rise. To the best of our knowledge, this is the first report of a GIST tumor overexpressing hCG.

Multi-institutional analysis of stereotactic body radiotherapy for sarcoma pulmonary metastases: High rates of local control with favorable toxicity.

BACKGROUND/OBJECTIVES: Oligometastatic sarcoma pulmonary metastases (PM's) are traditionally treated with resection and/or chemotherapy. We hypothesize that stereotactic body radiotherapy (SBRT) is an effective, safe alternative to surgery that can achieve excellent local control (LC) with a favorable toxicity profile. METHODS: Patients treated with SBRT for sarcoma PM's from 2011 to 2016 at Massachusetts General Hospital and the University of Pennsylvania were included. Median dose was 50 Gy. Patients underwent computed tomography (CT) or positron emission tomography/CT Q3 months post-SBRT. RESULTS: 44 patients with 56 separate PM's were treated with SBRT. Median age was 59 (range 19-82). 82% received prior chemotherapy, 66% had prior pulmonary resections (range, 1-5 resections), and 32% received prior thoracic radiotherapy. Median lesion size was 2.0 cm (range, 0.5-8.1 cm). Median follow-up was 16 months and 25 months for patients alive at last follow-up. Overall survival at 12 and 24 months was 74% (95% confidence interval [CI], 67%-81%) and 46% (95% CI, 38%-55%). LC at 12 and 24 months was 96% (95% CI, 93%-98%) and 90% (95% CI, 84%-96%). LC and overall survival did not differ based on age, gender, histology, fractionation, lesion location, or size (P > .05). Three developed Common Terminology Criteria for Adverse Events version 4 grade-2 chest-wall toxicities; one had grade-2 pneumonitis. CONCLUSIONS: In the first multi-institutional series on SBRT for sarcoma PM's, SBRT has excellent LC and is well-tolerated. SBRT should be considered as an alternative/complement to resection.

A prospective clinical trial of proton therapy for chordoma and chondrosarcoma: Feasibility assessment.

BACKGROUND/OBJECTIVES: Proton therapy (PRT) has emerged as a treatment option for chordomas/chondrosarcomas to escalate radiation dose more safely. We report results of a phase I/II trial of PRT in patients with chordoma/chondrosarcoma. METHODS: Twenty adult patients with pathologically confirmed, nonmetastatic chordoma or chondrosarcoma were enrolled in a single-institution prospective trial of PRT from 2010 to 2014. Seventeen patients received adjuvant PRT and three received definitive PRT. Median dose was 73.8 Gy(RBE; range 68.4-79.2 Gy) using PRT-only (n = 6) or combination PRT/intensity-modulated radiotherapy (IMRT) (n = 14). Quality-of-life (QOL) and fatigue were assessed weekly and every 3 months posttreatment with the Functional Assessment of Cancer Therapy - Brain (FACTBr) and Brief Fatigue Inventory. Primary endpoint was feasibility (90% completing treatment with < 10 day treatment delay and ≤ 20% unexpected acute grade ≥ 3 toxicity). RESULTS: Tumors included chordomas of the skull base (n = 10), sacrum (n = 5), and cervical spine (n = 3), and skull base chondrosarcomas (n = 2). Median age was 57. The 80% had positive margins/gross disease. Median follow-up was 37 months. Feasibility endpoints were met. The 3-year local control and progression-free survival was 86% and 81%. There were no deaths. Two patients had acute grade 3 toxicity (both fatigue). One had late grade 3 toxicity (epistaxis and osteoradionecrosis). There were no significant differences in patient reported fatigue or QOL from baseline to the end-of-treatment. CONCLUSIONS: We report favorable local control, survival, and toxicity following PRT.

Treatment Patterns and Overall Survival Outcomes of Octogenarians with Muscle Invasive Cancer of the Bladder: An Analysis of the National Cancer Database.

PURPOSE: Elderly patients with muscle invasive bladder cancer can pose a therapeutic dilemma, given multiple comorbidities which may preclude surgery. In this registry based analysis we investigated treatment patterns and survival outcomes in this group of patients. MATERIALS AND METHODS: We queried the National Cancer Database for muscle invasive (cT2-T4aN0M0) bladder cancer in patients 80 years old or older who were diagnosed from 2004 to 2013. Patients included in study underwent transurethral resection of bladder tumor followed by radical cystectomy, radical cystectomy plus chemotherapy, radiation therapy alone, chemotherapy alone, chemoradiation or no treatment. We performed Kaplan-Meier, log rank and multivariate Cox proportional hazards regression and propensity score matching. RESULTS: A total of 9,270 patients were identified with a median followup of 12.8 months. Median overall survival in patients treated with radical cystectomy alone was 23.2 months (95% CI 19.8-26.6), which was superior to that of chemotherapy alone or radiation therapy alone (p <0.0001). Those treated with chemoradiation had a median overall survival of 27.3 months (95% CI 25.0-29.7), which did not statistically differ from that of radical cystectomy alone (p = 0.39). Surgery plus chemotherapy showed the longest median overall survival of 34.5 months (95% CI 22.2-46.7, vs chemoradiation and radical cystectomy alone p <0.0001). On multivariate analysis and propensity score matching the best overall survival was seen in patients treated with surgery plus chemotherapy and there was no difference in overall survival between chemoradiation and radical cystectomy alone. CONCLUSIONS: In elderly patients with muscle invasive bladder cancer chemoradiation is an alternative definitive treatment strategy with survival equal to that of surgery alone and superior to that of chemotherapy alone or radiation therapy alone. If a patient was able to receive neoadjuvant or adjuvant chemotherapy with surgery, additional survival was observed in this nonrandomized study.

Neutrophil-to-lymphocyte ratio as a bladder cancer biomarker: Assessing prognostic and predictive value in SWOG 8710.

BACKGROUND: Risk stratification is a major challenge in bladder cancer (BC), and a biomarker is needed. Multiple studies have reported the neutrophil-to-lymphocyte ratio (NLR) as a promising candidate; however, these analyses have methodological limitations. Therefore, the authors performed a category B biomarker study to test whether NLR is prognostic for overall survival (OS) after curative treatment or is predictive for the survival benefit from neoadjuvant chemotherapy (NAC). METHODS: This study is an unplanned secondary analysis of SWOG 8710, a randomized phase 3 trial that assessed cystectomy with or without NAC in 317 patients with muscle-invasive BC. NLR was calculated from prospectively collected complete blood counts. For the prognostic analysis, 230 patients were identified; for the predictive analysis, 263 were identified. NLR was evaluated with proportional hazards models including prespecified factors (age, sex, T-stage, lymphovascular invasion, and treatment arm). RESULTS: With a median follow-up of 18.6 years, there were 172 and 205 deaths in the prognostic and predictive cohorts, respectively. In a multivariable analysis, NLR was not prognostic for OS (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.98-1.11; P = .24). Furthermore, NLR did not predict for the OS benefit from NAC (HR, 1.01; 95% CI, 0.90-1.14; P = .86). Factors associated with worse OS were older age (HR, 1.05; 95% CI, 1.04-1.07; P < .001) and surgery without NAC (HR, 1.39; 95% CI, 1.03-1.88; P = .03). CONCLUSIONS: This is the first analysis of NLR in BC to use prospectively collected clinical trial data. In contrast to previous studies, it suggests that NLR is neither a prognostic nor predictive biomarker for OS in muscle-invasive BC. Cancer 2017;123:794-801. © 2016 American Cancer Society.

Efficacy and safety of stereotactic body radiation therapy for the treatment of pulmonary metastases from sarcoma: A potential alternative to resection.

BACKGROUND/OBJECTIVES: Oligometastatic sarcoma pulmonary metastases (PM) are typically treated with resection and/or chemotherapy. We hypothesize that stereotactic body radiotherapy (SBRT) can be an alternative to surgery that can achieve high rates of local control (LC) with limited toxicity. METHODS: Thirty consecutive sarcoma patients received SBRT to 39 PM's from 2011 to 2015 at two university hospitals to a median dose of 50 Gy in 4-5 fractions with CyberKnife or linear accelerator. Patients underwent CT or PET/CT scans q3 months after SBRT. RESULTS: 77% received prior chemotherapy, 70% had 1-3 prior pulmonary resections, and 26% received prior thoracic radiotherapy. Median lesion size was 2.4 cm (range 0.5-8.1 cm). Median follow-up was 16 and 23 months for patients alive at last follow-up. At 12 and 24 months, LC was 94% and 86%, and OS was 76% and 43%. LC and OS did not differ by SBRT technique, fractionation regimen, lesion location, histology, or size (all P > 0.05). Three developed grade 2 chest-wall toxicity with no other grade ≥2 toxicities. CONCLUSIONS: This is the largest series on SBRT for sarcoma PM's and demonstrates that SBRT is well-tolerated with excellent LC across tumor locations and sizes. SBRT should be considered in these patients, and prospective studies are warranted. J. Surg. Oncol. 2016;114:65-69. © 2016 Wiley Periodicals, Inc.