Christopher Gaffney’s research while affiliated with Memorial Sloan Kettering Cancer Center and other places

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Publications (39)


Accelerating Drug Development in Hormone-Naïve Prostate Cancer and Changing the Paradigm from Palliation to Cure: The Metacure Phase 2 Randomized Clinical Trial
  • Preprint

January 2024

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7 Reads

Deaglan McHugh

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Min Yuen Teo

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Sean McBride

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[...]

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Howard I. Scher

Feasibility and tissue concordance of genomic sequencing of urinary cytology in upper tract urothelial carcinoma

August 2023

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18 Reads

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5 Citations

Urologic Oncology Seminars and Original Investigations

Background: There is limited ability to accurately diagnose and clinically stage patients with upper tract urothelial carcinoma (UTUC). The most easily available and widely used urinary biomarker is urine cytology, which evaluates cellular material yet lacks sensitivity. We sought to assess the feasibility of performing next-generation sequencing (NGS) on urine cytology specimens from patients with UTUC and evaluate the genomic concordance with tissue from primary tumor. Methods: In this retrospective study, we identified 48 patients with a diagnosis of UTUC treated at Memorial Sloan Kettering Cancer Center (MSK) between 2019 and 2022 who had banked or fresh urine samples. A convenience cohort of matching, previously sequenced tumor tissue was used when available. Urine specimens were processed and the residual material, including precipitated cell-free DNA, was sequenced using our tumor-naïve, targeted exome sequencing platform that evaluates 505 cancer-related genes (MSK-IMPACT). The primary outcome was at least 1 detectable mutation in urinary cytology specimens. The secondary outcome was concordance to matched tissue (using ANOVA or Chi-Square, as indicated). Results: Genomic sequencing was successful for 45 (94%) of the 48 urinary cytology patient samples. The most common mutations identified were TERT (62.2%), KMT2D (46.7%), and FGFR3 (35.6%). All patients with negative urine cytology and low-grade tissue had successful cytology sequencing. Thirty-six of the 45 patients had matching tumor tissue available; concordance to matched tissue was 55% overall (131 of the total 238 oncogenic or likely oncogenic somatic mutations identified). However, in 94.4% (n = 34/36) of patients, the cytology had at least 1 shared mutation with tissue. Eleven (30.6%) patients had 100% concordance between cytology and tissue. Conclusions: Sequencing urinary specimens from selective UTUC cytology is feasible in nearly all patients with UTUC. Prospective studies are underway to investigate a clinical role for this promising technology.


An in-progress phase 2 window of opportunity (WOO) trial of targeted therapy with erdafitinib for patients with recurrent FGFR3-altered non–muscle-invasive bladder cancer (NMIBC).

June 2023

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15 Reads

Journal of Clinical Oncology

TPS4614 Background: Alterations to FGFR3 are the most common somatic mutations in non-muscle invasive bladder cancer (NMIBC), present in 40-60% of high-grade Ta and > 80% of recurrent low grade Ta tumors. FGFR3 mutations are also known to be associated with a “cold” tumor microenvironment (TME) that may mediate BCG resistance. Erdafitinib, a targeted inhibitor of FGFR 1-4, is the first FDA approved targeted therapy for locally advanced/metastatic bladder cancer. As FGFR3 mutations are present 3-5x more commonly in NMIBC than metastatic disease, erdafitinib is a logical therapeutic candidate for FGFR3-altered NMIBC. Through this ongoing phase II trial, we seek to determine the safety and efficacy of erdafitinib for the treatment of intermediate and high risk FGFR3-altered NMIBC after prior intravesical therapy. Methods: To address the need for expanded targeted therapeutics for NMIBC, , we launched an investigator-initiated phase II window of opportunity (WOO) trial of erdafitinib (NCT04917809, PI Pietzak). We are currently enrolling patients with intermediate or high risk NMIBC with history of ≥1 or more induction courses of BCG and/or intravesical chemotherapy who present with a clinically staged Ta papillary recurrence on office cystoscopy. Patients are also required to have an oncogenic FGFR3 mutation or fusion, as confirmed by OncoKB on MSK-IMPACT, to be included in the trial. Trial patients are treated with 6 mg oral erdafitinib daily for 28 days during the “window of opportunity” time period between office cystoscopy and transurethral resection of the recurrent bladder tumor (TURBT). The primary outcome is the rate of objective response, defined as complete (no visible tumor) or partial ( > 50% reduction of measured diameter by Response Evaluation Criteria for Tumors of the Bladder [RECIT-Bladder]) as compared to cystoscopy at TURBT. We are employing an optimal Simon two-stage binomial design, assuming an objective response of > 15% would and < 2% would not be worthy of further study. We plan to enroll 16 patients in the first stage and 9 in the second (87% power). Secondary outcomes include safety (CTAE 5.0), patient reported outcomes, and recurrence-free survival. Correlative studies will be conducted with urine, blood, and tumor tissue samples. Urine and blood are collected before (day 1), during (day 14) and after treatment (day 28) and will undergo immune and molecular studies to understand shifts in the microenvironment in the setting of response and resistance. This trial is being conducted in parallel with a co-clinical trial of patient derived organoid/xenograft models (MSK 19-015, PI Pietzak) to further refine the understanding of FGFR3 mutational resistance to standard treatment and the effects of targeted immunotherapy on tumor clinicogenomics. Clinical trial information: NCT04917809 .


A brief mind-body intervention to reduce pain and anxiety during prostate needle biopsy: A randomized, controlled trial with two-staged consent.

June 2023

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6 Reads

Journal of Clinical Oncology

e17092 Background: Prostate biopsy is among the most common oncologic procedures performed annually. A substantial proportion of patients experience significant morbidity related to biopsy, including pain, anxiety, and discomfort which may discourage follow-up biopsy crucial for identifying progression or discourage enrollment in active surveillance programs that require serial biopsy. Guided meditation significantly reduces pain and anxiety during breast biopsy. We developed a brief mind-body intervention that could easily integrate into general practice for patients during prostate biopsy and compared patient-reported outcomes after biopsy with and without this intervention. Methods: We conducted a clinically-integrated randomized controlled trial (MSK IRB 18-089) of a brief mind-body intervention during prostate biopsy compared to usual care. All adult patients offered biopsy were eligible. Patients randomized to the intervention were offered both a pre-biopsy mind-body exercise and guided mindfulness meditation during biopsy via headphones. The primary outcome of interest was any severe patient-reported pain, anxiety, discomfort, or tolerability on a visual-analog scale (0-10). We compared the proportion of men in each arm reporting a severe score (7-10) on any of the four scales using Fisher’s exact test. The pre-specified clinically relevant improvement justifying integration into clinical practice was 15%. We compared means separately using ANCOVA with randomization stratum (first vs. prior biopsy) as a covariate. Results: 238 patients (119 per arm) enrolled. 102 in the intervention arm and 94 in the usual care arm proceeded to biopsy and completed the questionnaire. A total of 37/94 (39%) and 38/102 (37%) patients in the usual care and the intervention arms, respectively, reported severe scores in any of the four domains, a difference of 2.1% (95% confidence interval -13, 17%, p = 0.8). The upper bound of the confidence interval includes the pre-specified clinically relevant difference. There was no evidence of a difference in mean post-biopsy anxiety (p = 0.3), discomfort (p = 0.09), pain (p = 0.4) or tolerability scores (p = 0.2), Table. Conclusions: There was no difference in patient reported outcomes between a mind-body intervention and usual care for prostate biopsy. Though the upper bound of the 95% confidence interval included the clinically relevant difference in severe scores, the difference in means for each outcome suggests a clinically meaningful benefit for this brief mindfulness intervention is unlikely. [Table: see text]


Adoption and Outcomes of HoLEP in the United States

June 2023

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31 Reads

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4 Citations

Urology

Objectives: To investigate the utilization of holmium laser enucleation of the prostate (HoLEP) using a large real-world cohort. We compare the safety, readmission, and retreatment rates of HoLEP to other widely used endoscopic surgical interventions for benign prostatic hyperplasia (BPH) including transurethral resection of the prostate (TURP), photoselective vaporization of the prostate (PVP), and prostatic urethral lift (PUL). Methods: Men who underwent endoscopic treatments for BPH from 2000-2019 were identified in the Premier Healthcare Database (n=218,793). We compared the relative proportion of each procedure performed and annual physician volume data to identify trends in adoption and utilization. Readmission and retreatment rates were determined at both 30- and 90- days post-operation. Multivariable logistic regression was used to assess the association between procedure type and outcomes. Results: HoLEP accounted for 3.2% (n=6,967) of all BPH procedures performed between 2000 and 2019 and increased from 1.1% of procedures in 2008 to 4% in 2019. Patients undergoing HoLEP had a lower odds of 90-day readmission compared to TURP (OR 0.87, p=0.025). HoLEP had similar odds of retreatment compared to TURP at both 1- year (OR 0.96, p=0.7) and 2-years (OR 0.98, p=0.9), while patients undergoing PVP and PUL were more likely to be retreated within 2-years (OR 1.20, p<0.001; OR 1.87, p<0.001). Conclusions: HoLEP is a safe therapy for BPH with lower readmission and comparable retreatment rates to the gold standard TURP. Despite this, the utilization of HoLEP has lagged behind other endoscopic procedures and remains low.






A phase II trial of intravesical chemoimmunotherapy with gemcitabine and bacillus Calmette-Guérin (BCG) for patients with BCG-exposed, high-grade, non-muscle–invasive bladder cancer.

February 2023

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13 Reads

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1 Citation

Journal of Clinical Oncology

TPS579 Background: The standard of care for high-risk non-muscle invasive bladder cancer (NMIBC) after exposure to induction only BCG or relapse >12 months after “adequate” BCG is retreatment with BCG. However, ~50% of patients will relapse within 6 months. Thus, there is a critical need to develop novel combination therapies to improve BCG immunotherapy efficacy. Combination BCG with immune checkpoint inhibition is associated with a ~12-18% risk of serious treatment-related adverse events and BCG combined with Mitomycin C (MMC) has unacceptable urinary toxicity. Intravesical Gemcitabine (GEM) is a common treatment for NMIBC, is well tolerated, has better efficacy after BCG than MMC, and, based on preclinical data, may synergistically enhance the efficacy of BCG by augmenting the immune tumor microenvironment. We completed a prospective Phase I trial of chemoimmunotherapy with gemcitabine and BCG in BCG-relapsed/BCG-exposed NMIBC that was well-tolerated (no treatment related grade ≥3 adverse events) with promising early efficacy (95% [19/20] 6-month complete response rate). No dose limiting toxicities were seen. The maximum tolerated dose (MTD) was 2000 mg gemcitabine and 50 mg TICE BCG. Methods: To address the need for more effective and less toxic bladder preserving treatment options by enhancing the effectiveness of BCG, we launched an investigator-initiated phase I/II trial of combination intravesical gemcitabine with BCG in patients with BCG-exposed NMIBC (NCT04179162). The Phase II portion is currently enrolling patients with BCG-exposed carcinoma in-situ (CIS ±Ta/T1) that recurred within 24 months of last BCG (BCG-exposed/BCG-relapsing NMIBC). Patients with BCG-unresponsive disease, contraindication to BCG, or prostatic/ureteral urothelial disease are excluded. Induction intravesical GEM (2000mg, twice weekly) is given weeks 1, 4, 7, and 10 and intravesical BCG (40mg, Tice strain, weekly) is given weeks 2, 3, 5, 6, 8, and 9. Responders receive SWOG maintenance BCG. The primary endpoint is clinical complete response (CR) at 6 months (absence of high-grade disease on cystoscopy/TURBT and negative cytology) using a Simon’s optimal 2-stage design testing the null hypothesis of a true CR of 55% at 6 months (based on historical outcomes of BCG alone) against a 1-sided alternative. In the first stage, the study would stop if ≤ 9/15 patients had a CR. In the second stage, the null hypothesis will be rejected if ≥ 29 CRs are observed in 43 total patients (type I error rate 5% and power of 80% if the true CR rate is 75%). Phase I patients treated at the MTD (14/25) are included in Phase II. Secondary outcomes include recurrence-free, progression-free, and cystectomy-free survival. Correlative studies explore immune and molecular predictors of response and resistance to chemoimmunotherapy in tumor tissue, urine, and blood. Clinical trial information: NCT04179162 .


Citations (15)


... The results of this study corroborate recent studies on urinary samples. Katims et al. [14] found that targeted gene sequencing was possible in urinary cytology in 95% of cases. In their study, all patients with negative cytology samples were successfully sequenced [14]. ...

Reference:

Diagnostic and prognostic genomic aberrations in upper tract urothelial carcinoma can be identified in focal barbotage samples
Feasibility and tissue concordance of genomic sequencing of urinary cytology in upper tract urothelial carcinoma
  • Citing Article
  • August 2023

Urologic Oncology Seminars and Original Investigations

... TURP has been the gold standard in surgery for BPH for decades 3,36 . Laser-enucleation still has a niche existence in comprehensive healthcare 36,37 , but may gain in popularity, reaching a share of 20% in surgeries for BPH performed in France in 2018, and may increasingly replace TURP or emerged as the preferred option in centers with corresponding expertise [38][39][40] . HoLEP and ThuLEP equally relieve voiding symptoms, with high efficacy and safety 41 . ...

Adoption and Outcomes of HoLEP in the United States
  • Citing Article
  • June 2023

Urology

... Intravesical therapy continues to evolve, especially with recent trials investigating novel combination intravesical chemotherapy regimens [61][62][63]. In patients with BCG-unresponsive NMIBC, combination therapy may be a highly effective therapeutic option. ...

A phase II trial of intravesical chemoimmunotherapy with gemcitabine and bacillus Calmette-Guérin (BCG) for patients with BCG-exposed, high-grade, non-muscle–invasive bladder cancer.
  • Citing Article
  • February 2023

Journal of Clinical Oncology

... In addition, the limited amount of eligible studies reduced the credibility of the final conclusions. Another nine articles [12,[14][15][16][17][18][19][20][21] were added to this research compared to the latest meta-analysis [13], which made the outcomes more convincing and credible. Gald conducted an additional stratified analysis utilizing the semen concentration of the patients [20]. ...

Impact of testicular delivery and vasal vein ligation on clinical outcomes in men undergoing microsurgical varicocelectomy
  • Citing Article
  • Publisher preview available
  • December 2021

International Urology and Nephrology

... More recently, improvements in endourologic instrumentation have permitted minimally invasive approaches to ejaculatory duct pathology, such as seminal vesiculoscopy or balloon dilation of the ejaculatory ducts [35,36]. Unusual pathology may be encountered, such as symptomatic stones requiring laser lithotripsy or basketing, blood clots requiring irrigation, or tumors necessitating biopsy [37,38]. ...

V07-10 SEMINAL VESICULOSCOPY FOR DIAGNOSIS AND MANAGEMENT OF HEMATOSPERMIA
  • Citing Article
  • September 2021

The Journal of Urology

... Several studies have compared the clinical outcomes between unilateral VE and bilateral VE (13,17,18), however no studies have focused on the efficacy of unilateral VE in OA of different causes. To the best of our knowledge, this is the first study reporting the clinical outcomes of unilateral VE between congenital and acquired OA patients. ...

Practice patterns of vasal reconstruction in a large United States cohort
  • Citing Article
  • August 2021

... New modalities and approaches have expanded the indications for the surgical treatment of BPH [6,7]. For example, GreenLight photovaporization of the prostate (PVP) has been shown to reduce the risk of intraoperative bleeding and postoperative hematuria in patients requiring anticoagulant and/or antiplatelet therapy, and has been associated with lower rates of major acute cardiac events [8][9][10]. ...

Symptomatic Improvement of Lower Urinary Tract Symptoms of Benign Prostatic Hyperplasia: A Comparative Systematic Review and Meta-Analysis of Four Different Minimally Invasive Therapies
  • Citing Article
  • July 2021

Journal of Vascular and Interventional Radiology

... If the tumor sizes > 8 mm in the biopsies, the likelihood is 90% to be upgraded from GS6 to GS7 in the prostatectomy specimens [32]. Molecular studies show that tumor size is an independent factor in the accumulation of genomic risk factors [33]. Furthermore, molecular studies have shown that even small foci can metastasize [34]. ...

Tumor size and genomic risk in localized prostate cancer
  • Citing Article
  • February 2021

Urologic Oncology Seminars and Original Investigations

... A recent national survey of urologists and radiation oncologists showed that while both specialties reported positive attitudes towards mpMRI, only about a quarter of providers in both groups actually ordered mpMRI [1]. Likewise, a recent review of SEER data showed that while more people are using mpMRI in men with prior biopsy and no prior biopsy, there remains significant heterogeneity in utilization patterns, with increased utilization reported in patients with higher socioeconomic status [2]. e findings suggest that one of the main factors limiting the accessibility of mpMRI is its affordability [3]. ...

MP42-18 INCREASING UTILIZATION OF MAGNETIC RESONANCE IMAGING (MRI) PRIOR TO PROSTATE BIOPSY IN BLACK AND NON-BLACK MEN: AN ANALYSIS OF THE SEER-MEDICARE COHORT
  • Citing Article
  • April 2020

The Journal of Urology