Faculty Bibliography

PURPOSE/OBJECTIVE:This prospective, non-randomized phase II single-arm pilot trial aimed to explore favorable mid-treatment nodal response (FMNR) through CT imaging to guide de-escalated chemoradiation therapy (CRT) in patients with favorable risk, node-positive HPV-associated oropharyngeal cancer (OPC). MATERIALS AND METHODS/METHODS:. At week 4, CT imaging evaluated nodal response: ≥40% reduction warranted de-escalation to 60 Gy, while <40% reduction continued standard CRT. Primary endpoint was 2-year PFS from initiation of dose de-escalated CRT. Tissue tumor modified viral (TTMV) HPV DNA samples and DW-MRI were collected at baseline and week 4. MDADI questionnaires were collected at baseline, 1, 3, 6, 12, and 24 months. RESULTS:Of 39 patients, 26 had FMNR and underwent de-escalated treatment. 13 pts had slow mid-treatment nodal shrinkage and received standard dose. At a median follow-up of 47.4 months, the 2-year PFS was 92.1% (95% CI: 0.72-0.98) for the deescalated dose group and 92.3% for the standard dose patients (95% CI: 0.57-0.99), p=0.96. With a median survival follow up of 48.9 months (range: 16.7-77.8 months), there were no deaths or distant failures. FMNR was associated with rapid TTMV HPV DNA clearance, reduced TTMV HPV DNA flare, lower baseline and week 4 MRI diffusivity, and higher baseline and week 4 MRI diffusional kurtosis. No differences in acute or late maximum grade 3-4 toxicity by patient were noted. MDADI composite scores showed minimal clinical important difference (MCID) in the de-escalated group at 1-month post-treatment while the standard group had MCID up to 1-year post-treatment. No patients required feeding tube placement. CONCLUSIONS:De-escalated CRT using CT-based mid-treatment nodal response in favorable risk, node-positive HPV-associated OPC achieved excellent 2-year PFS and OS rates and represents a potential approach in better selecting patients for treatment de-escalation.

PURPOSE/OBJECTIVE:Pelvic nodal irradiation is often used for high-risk prostate adenocarcinoma. A commonly used alternative to low dose rate (LDR) brachytherapy, a 3-fraction SBRT boost with fiducial tracking may allow for better coverage of extracapsular extension and macroscopic seminal vesicle invasion. This study evaluates the practical impact of prior pelvic nodal irradiation on fiducial tracking during a subsequent 3-fraction robotic stereotactic body radiation therapy (SBRT) boost for high-risk prostate cancer and compares these outcomes to a cohort of patients undergoing definitive 5-fraction SBRT. METHODS:In this institutional analysis, we prospectively collected fiducial tracking data for patients receiving a 3-fraction boost to the prostate and seminal vesicles after conventional nodal radiation. We also identified patients treated with 5-fraction SBRT with a low risk of nodal involvement. Monte Carlo estimates of the Fisher's Exact Test assessed fiducial tracking loss. Continuous variables within the 5- and 3-fraction cohorts were compared using the Mann-Whitney Test. Changes in fiducial tracking and their association with pre-treatment factors were analyzed through the Kruskal-Wallis test and Monte Carlo for tracking patterns, and Spearman Correlation Coefficient and Mann-Whitney Test for deviations in tracking over 5 fractions. RESULTS:A total of 405 patients were treated from April 2021 to September 2023 with: (1) 5-fraction SBRT (n = 309, 76%), and (2) 3-fraction boost after nodal irradiation (n = 96, 24%). There was no significant fiducial tracking loss over the three-fraction boost treatment regimen that proceeded nodal treatment (p = 0.63). However, there was a significant (p < 0.001) loss of fiducial tracking fidelity as demonstrated by progressive loss of one tracked fiducial over 5-fractions. There was significantly more volatility observed in the 5-fraction versus 3-fraction boost treatment (median volatility 2.4 vs. 0.0, p < 0.001). There were no significant associations between fiducial tracking, independently for 3- or 5-fractions, using either analysis method or volatility for ADT, time from fiducial placement to SBRT, CTV, and QOD vs. daily SBRT. CONCLUSIONS:Pelvic nodal treatment does not affect the quantity/quality of fiducial tracking in 3-fraction treatments. However, 5-fraction treatments showed a progressive loss and increased volatility in fiducial tracking over time. No pre-treatment factors significantly influenced fiducial tracking changes in either cohort, though ADT use trended towards increased volatility in the 5-fraction group. With a minimum of 4 fiducials placed for treatment, the loss/volatility of a single fiducial had no clinical impact on the tracking system.

PURPOSE/OBJECTIVE:Locoregionally recurrent head and neck cancer is a complex clinical scenario that often requires multimodality treatment. These patients have often previously received definitive treatment with a combination of surgery, radiation therapy, and systemic therapy, which can make further management difficult. A second isolated locoregional failure is rare and clinicians are faced with a challenge to optimize disease control while minimizing treatment-related toxicity. METHODS AND MATERIALS/METHODS:In this report, we present the diagnosis, management, and outcomes of a patient with an isolated locoregional recurrence who was previously treated with two courses of radiation. The patient was treated with a second course of reirradiation using interstitial brachytherapy as well as a discussion regarding patient selection and optimal management for recurrent head and neck cancer. RESULTS:Repeat reirradiation using interstitial HDR-brachytherapy with the use of an alloderm spacer was successfully delivered to the patient for an in-field right neck nodal recurrence. He received a total EQD2/BED dose of 127.70/153.24 Gy. At 1-year followup, the patient was without evidence of recurrent disease or new significant side effects. CONCLUSION/CONCLUSIONS:Recurrent head and neck cancer should be managed with a multidisciplinary approach given the complex clinical scenario. Reirradiation is a commonly used salvage measure for recurrent head and neck cancer that requires careful planning and patient selection due to prior treatment-related effects and dose constraints. We reported a case of a second course of reirradiation using interstitial HDR-brachytherapy for locoregionally recurrent head and neck cancer and showed no recurrence of disease or worsening long term side effects at 1 year.

BACKGROUND/PURPOSE/UNASSIGNED:The optimal management of residual micrometastases and isolated tumor cells (ITC) in patients with invasive breast cancer who undergo neoadjuvant chemotherapy (NAC) followed by definitive surgery is not well-studied. We evaluated the role of regional nodal irradiation (RNI) in clinically node-positive (cN1) breast cancer patients with residual low-volume nodal disease following NAC. METHODS/MATERIALS/UNASSIGNED:We queried the National Cancer Database (NCDB) and included patients with cN1 invasive breast cancer diagnosed from 2004 to 2016 who were treated with NAC and definitive surgery and had residual micrometastases (ypN1mi) or ITC (ypN0i+). We used univariable (UVA) and multivariable (MVA) Cox regression analyses to determine prognostic factors and Kaplan-Meier (KM) methods to evaluate overall survival (OS). We used inverse probability treatment weighting (IPTW) to reweight data to account for confounding factors. RESULTS/UNASSIGNED:Our final cohort included 1980 patients, including 527 patients with ypN0i + disease and 1453 patients with ypN1mi disease. 1101 patients (45.0%) received RNI in the overall cohort with a higher proportion of ypN1mi patients receiving RNI (56.5%) compared to 53.1% of ypN0i + patients. There was no significant difference in OS between ypN0i + and ypN1mi patients. RNI had no significant effect on OS in the overall cohort using Cox MVA and KM methods. With separate subset analysis of ypN0i + and ypN1mi patients, there was no significant effect of RNI on OS. This was confirmed with IPTW. CONCLUSIONS/UNASSIGNED:In a national hospital-based study of cN1 invasive breast cancer patients with residual ITC or micrometastases after NAC, RNI did not have a significant effect on OS.

PURPOSE/OBJECTIVE:Squamous cell carcinoma (SCC) of the rectum is a unique entity that lacks definitive guidelines regarding prognosis and treatment. This study aimed to analyze patterns of care and survival for SCC and adenocarcinoma (AC) of the rectum. METHODS:This was a retrospective analysis of patients with stage I-III SCC or AC of the rectum treated from 2004 to 2016 from the National Cancer Database. The treatment groups analyzed were surgery alone (S), chemoradiation followed by surgery (CRT + S), surgery followed by chemoradiation (S + CRT), and definitive chemoradiation (CRT). Patient- and clinical-related factors were compared. Overall survival was assessed with the Kaplan-Meier method and Cox proportional regression models. RESULTS:Of the patients studied, 21,587 (97.1%) were AC and 640 (2.9%) were SCC. Among patients with AC, most (n = 8549, 59.4%) received chemoradiation followed by surgery; those with SCC (n = 305, 66.4%) received definitive chemoradiation. Among patients who received surgery, the majority (69.2%) with AC histology had a low anterior resection while the majority (52.1%) of SCC had an abdominoperineal resection. Five-year overall survival of AC versus SCC in the entire cohort was 61.6% versus 56.1%, respectively (p < 0.001). On multivariable analysis for AC, CRT + S (HR 0.61, p < 0.001), or S + CRT (HR 0.67, p < 0.001) had improved survival compared to S alone while those who had definitive CRT (HR 1.55, p < 0.001) had worse survival. CONCLUSIONS:SCC of the rectum tends to be treated like anal cancers with definitive chemoradiation, with similar survival to historical reports of anal cancer. AC of the rectum is most commonly treated under the rectal cancer paradigm.

We present the case of a 65-year-old male with tumor-induced osteomalacia (TIO) caused by an FGF23-secreting phosphaturic tumor of C2 treated definitively with stereotactic body radiation therapy (SBRT) and kyphoplasty. The patient exhibited notable reduction in FGF23 6 weeks following radiotherapy. He also received a dose of the FGF23 monoclonal antibody, burosumab. We discuss the case with emphasis on radiation in the management of TIO. This case demonstrates SBRT as a well-tolerated local treatment option for the management of unresectable FGF23-producing tumors.