Faculty Bibliography

BACKGROUND AND OBJECTIVE/OBJECTIVE:Trimodality therapy (TMT) is an accepted bladder-preserving option for selected patients with muscle-invasive bladder cancer (MIBC). Pembrolizumab has demonstrated activity in MIBC and may enhance the effects of chemotherapy and radiation. We evaluated the safety and efficacy of adding pembrolizumab to TMT. METHODS:In this multicenter phase 2 trial, patients with MIBC received one dose of pembrolizumab followed by maximal transurethral resection, then definitive bladder radiation with concurrent low-dose gemcitabine and pembrolizumab every 3 wk for three doses. The primary end point was 2-yr bladder-intact disease-free survival (BIDFS). Secondary end points included safety, metastasis-free survival (MFS), and overall survival (OS). KEY FINDINGS AND LIMITATIONS/UNASSIGNED:Fifty-four patients were enrolled, including 48 in the efficacy cohort; 67% had clinical stage T2 disease. The 2-yr BIDFS was 60% (95% confidence interval [CI], 45-73). Two-yr MFS and OS were 81% (95% CI, 66-92) and 83% (95% CI, 69-91), respectively. Grade ≥3 treatment-related adverse events occurred in 25% of patients. Limitations include the single-arm design and modest sample size. CONCLUSIONS AND CLINICAL IMPLICATIONS/CONCLUSIONS:Pembrolizumab combined with gemcitabine-based chemoradiation was feasible and showed efficacy comparable to standard TMT. Ongoing phase 3 trials will further define its role in bladder preservation.

INTRODUCTION/BACKGROUND:Focal dose intensification strategies targeting the dominant intra-prostatic lesion (DIL) improve outcomes of patients with prostate cancer. The purpose was to determine whether the 6-month multiparametric (mp)MRI response of the DIL is associated with post-treatment prostate-specific antigen (PSA) kinetics after MRI linear accelerator (LINAC) guided stereotactic body radiotherapy (SBRT) with focal dose intensification. METHODS:), and PSA ≤ 1.0 ng/mL. RESULTS:(100.0% vs 82.9%, p = 0.010) and PSA ≤ 1.0 ng/mL (45.9% vs 11.4%, p = 0.001) compared to those without mpMRI CR. In 10 patients without 6-month mpMRI CR but had further MRI follow-up (median 13 months), DILs either further decreased in size (30.0%) or resolved (70.0%). CONCLUSION/CONCLUSIONS:Initial 6-month mpMRI response correlates with PSA kinetics, which is associated with important clinical outcomes. mpMRI can be used for post-SBRT evaluation to gauge local tumor response of the DIL, where most recurrences occur.

OBJECTIVE:This study aimed to explore the demographic and clinical factors associated with delayed initiation of treatment for patients with cervical cancer treated with chemoradiation and brachytherapy and determine its impact on oncologic outcomes. METHODS:Patients with stage IB2 to IVA cervical cancer who were treated with definitive chemoradiation therapy and brachytherapy from 2009 to 2019 were included. Patients who initiated treatment within 8 weeks of diagnosis (early) were compared with those who initiated treatment after 8 weeks (delayed). Time intervals at each stage of care and reasons for delay were evaluated. Logistic regression was performed to identify factors associated with delayed treatment initiation. Cox regression analyzed factors associated with progression-free and overall survival. RESULTS:Of 122 patients, 76 (62%) initiated early treatment, with a median time to treatment of 35 days, and 46 (38%) underwent delayed treatment initiation, with 76 median days to treatment. Patients referred from the public hospital were more likely to experience delayed treatment than those referred from the private hospital (odds ratio 4.31, 95% confidence interval [CI] 1.31 to 14.07). Most delays were due to system factors (85%). Each 10-day increase in time to treatment initiation was associated with worsened overall survival (hazard ratio [HR] 1.07, 95% CI 1.01 to 1.13). Public hospital patients were more likely to experience delays but were less likely to present with advanced stage (29% vs 50%, p = .031) and had improved overall survival compared with patients referred from the private hospital (HR 0.37, 95% CI 0.16 to 0.87). CONCLUSIONS:Treatment initiation delays were associated with a decrement in survival. In this cohort, public hospital patients were more likely to have a favorable stage and improved survival than those from the private hospital but also were more likely to experience treatment initiation delays. Referral patterns and delays related to diagnostic workup were the most common factors contributing to delays in care establishment. Improving care coordination may ensure equitable access to timely staging and treatment. Further studies are needed to determine whether treatment initiation delays impact cancer outcomes.

Post-radiotherapy erectile dysfunction (ED) can significantly impact the quality of life of patients with prostate cancer (PCa). Critical anatomical structures, such as the neurovascular bundle (NVB), internal pudendal arteries (IPA), penile bulb, and corporal tissues track in close proximity to the prostate, making them susceptible to radiation-related damage. This study aimed to evaluate the anatomical patterns of these structures and their relationship with the prostate, and to provide comprehensive illustrative examples on MRI. Consecutive patients with PCa who underwent MRI-linear accelerator (LINAC)-based stereotactic body radiotherapy (SBRT) in January-December 2024 were included. NVB patterns were classified into 3 categories: (1) "classical" with discrete NVB elements, (2) "adherent", dispersed and adherent to prostatic capsule, and (3) "absent". The smallest distance between the IPA and the prostate capsule and membranous urethral length (MUL), serving as a surrogate for distance between corporal tissue and prostatic apex, were also measured. These MRI findings were compared between prostate volumes >40 and <40 ml and between MRI/pathological features of the dominant intraprostatic lesion. A total of 160 men (median age 70 years, interquartile range [IQR] 64-76) were included. The most common NVB pattern was "classic" (80.0-85.0%), followed by the "adherent" NVB pattern (13.8-18.1%). The median smallest distance between the IPA and prostate was 2.3 cm (IQR 1.8-2.8 cm), with 3.1-3.8% less than 1.0 cm. The median MUL was 1.5 cm (IQR, 1.2-1.8 cm), with 2.5% of patients less than 1.0 cm. No significant association was found between these MRI features and prostate volume or other variables (p = 0.09-0.99). In conclusion, most PCa patients demonstrated favorable anatomy for potential dose sparing of critical structures. Comprehensive MRI illustrations are provided to help radiation oncologists recognize the location, trajectory, and relationship of these structures, facilitating their contouring and ultimately aiding in achieving meaningful dose reductions to these erectile function structures.

PURPOSE OF REVIEW/OBJECTIVE:The most common definitive treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy. However, removing the bladder and surrounding organs poses risks of morbidity that can reduce quality of life, and raises the risk of death. Treatment strategies that preserve the organs can manage the local tumor and mitigate the risk of distant metastasis. Recent data have demonstrated promising outcomes in several bladder-preservation strategies. RECENT FINDINGS/RESULTS:Bladder preservation with trimodality therapy (TMT), combining maximal transurethral resection of the bladder tumor, chemotherapy, and radiotherapy (RT), was often reserved for nonsurgical candidates for radical cystectomy. Recent meta-analyses show that outcomes of TMT and radical cystectomy are similar. More recent bladder-preservation approaches include combining targeted RT (MRI) and immune checkpoint inhibitors (ICIs), ICIs and chemotherapy, and selecting patients based on genomic biomarkers and clinical response to systemic therapies. These are all promising strategies that may circumvent the need for radical cystectomy. SUMMARY/CONCLUSIONS:MIBC is an aggressive disease with a high rate of systemic progression. Current management includes neoadjuvant cisplatin-based chemotherapy and radical cystectomy with lymph node dissection. Novel alternative strategies, including TMT approaches, combinations with RT, chemotherapy, and/or ICIs, and genomic biomarkers, are in development to further advance bladder-preservation options for patients with MIBC.

BACKGROUND AND PURPOSE/OBJECTIVE:Radiation dose prescriptions are foundational for optimizing treatment efficacy and limiting treatment-related toxicity. We sought to assess the lack of standardization of SBRT dose prescriptions across institutions. MATERIALS & METHODS/METHODS:were used to assess dosimetric variability. RESULTS: ≥ 110 % was found in nearly half of the institutions. There was significant dosimetric variation across institutions. CONCLUSIONS:The SBRT prescriptions in the literature or in treatment guidelines currently lack nuance and hence there is significant variation in dose prescriptions across academic institutions. These findings add greater importance to the identification of dose parameters associated with improved clinical outcome comparisons as we move towards more hypofractionated treatments. There is a need for standardized reporting to help institutions in adapting treatment protocols based on the outcome of clinical trials. Dosimetric parameters are subsequently needed for uniformity and thereby standardizing planning guidelines to maximize efficacy, mitigate toxicity, and reduce treatment disparities are urgently needed.

Purpose: Locally advanced cervical cancer was defined by an international consensus panel as a high priority malignancy during the COVID-19 pandemic, recommending prompt initiation of definitive treatment and completion of treatment (PMID 32563593). The objective of this study was to study the clinical outcomes of patients (pts) with cervical cancer treated with definitive chemoradiation (CRT) and brachytherapy (BT) at our institution in 2019 (pre-COVID) and in 2020 (peri-COVID).
Material(s) and Method(s): This was a retrospective cohort study of pts with FIGO Stage IB2-IVA cervical cancer at our institutions from 1/1/2019 to 12/31/2020. Pts received CRT followed by intracavitary brachytherapy (IC) with two operative insertions one week apart, or interstitial (IS) BT with one operative insertion. BT treatment was planned using image-guided CT or MR delineation. Pre-COVID was defined by initiation of CRT in 1/2019-12/2019, and peri-COVID was defined by initiation in 1/2020-10/2020. Process changes peri-COVID included limited on-site staff (e.g., minimal OR staff, no trainees, remote physics team), universal implementation of COVID-19 testing prior to surgery, and CT instead of MR-delineation based treatment. Outcomes of interest were time to treatment initiation and completion and differences in treatment planning modality or dosimetry. Fisher's exact and Mann Whitney U tests were used with significance p<0.05.
Result(s): Thirty-one pts were included, with 18 patients undergoing treatment pre-COVID and 13 peri-COVID. The median age at diagnosis pre-COVID was 57.7 (range 23-77) and for peri-COVID, 45.5 (range 28-62, p=0.06). There were no differences in non-English speaking pts (44% vs 59%, p=0.71) or uninsured pts (11% vs 33%, p=0.184) between the two cohorts. Median time to initiation of treatment from biopsy diagnosis was 52 days (range 13-209) in 2019 and for peri-COVID, 55.5 (range 20-173, p=0.71). During COVID, four pts had delayed initiation to treatment >100 days: two related to fertility, and one due to fear of COVID-19. For this pt, tumor size progressed from 2.3 cm to 4.2 cm maximal dimension. One pt treated in 2020 tested positive following treatment and did not require hospital admission. All pts except one completed CRT with RT: 25 pts pelvic RT (45 Gy), 3 pelvic and para-aortic RT (45 Gy with 57.5 Gy concomitant boost to nodes), 8 pts pelvic RT (45Gy) with sequential parametrial boost (50.4-59.4 Gy) using IMRT with no dose differences between pre and peri-COVID (Table 1). No pts required treatment breaks and the median overall treatment time was 50 days (range 31-85) in 2019 vs 50 days (range 43-63) in 2020 (p=0.710).
Conclusion(s): Despite the significant burden of the COVID-19 pandemic on our health care system, all cervical cancer pts receiving CRT met standard of care including CRT and BT within the recommended time frame with no significant differences in dosimetric treatment parameters pre- and peri-COVID. Delays in treatment initiation of treatment initiation were seen in 30% of pts in the peri-COVID period, suggesting that patients may have had increased barriers to access care. More follow-up is needed to determine how the Covid pandemic impacted cervical cancer outcome measures.
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Objectives/UNASSIGNED:To investigate the efficacy and safety of lung stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC) including oligorecurrent and oligoprogressive disease. Methods/UNASSIGNED:Single-institution retrospective analysis of 60 NSCLC patients with 62 discrete lesions treated with SBRT between 2008 and 2017. Patients were stratified into three groups, including early stage, locally recurrent, and oligoprogressive disease. Group 1 included early stage local disease with no prior local therapy. Group 2 included locally recurrent disease after local treatment of a primary lesion, and group 3 included regional or well-controlled distant metastatic disease receiving SBRT for a treatment naive lung lesion (oligoprogressive disease). Patient/tumor characteristics and adverse effects were recorded. Local failure free survival (LFFS), progression free survival (PFS), and overall survival (OS) were estimated using the Kaplan Meier method. Results/UNASSIGNED:At median follow-up of 34 months, 67% of the study population remained alive. The estimated 3-year LFFS for group 1, group 2, and group 3 patients was 95% (95% CI: 86%-100%), 82%(62% - 100%), and 83% (58-100%), respectively. The estimated 3-year PFS was 59% (42-83%), 40% (21%-78%), and 33% (12%-95%), and the estimated 3-year OS was 58% (41-82%), 60% (37-96%), and 58% (31-100%)), respectively for each group. When adjusted for age and size of lesion, no significant difference in OS, LFFS, and PFS emerged between groups (p > 0.05). No patients experienced grade 3 to 5 toxicity. Eighteen patients (29%) experienced grade 1 to 2 toxicity. The most common toxicities reported were cough and fatigue. Conclusions/UNASSIGNED:Our data demonstrates control rates in group 1 patients comparable to historical controls. Our study also reveals comparable clinical results for SBRT in the treatment of NSCLC by demonstrating similar rates of LFFS and OS in group 2 and group 3 patients with locally recurrent and treatment naïve lung lesion with well-controlled distant metastatic disease.

PURPOSE/OBJECTIVE(S): Use of local therapy such as stereotactic body radiation therapy (SBRT) to treat oligometastatic malignancy is a well-established paradigm, but whether benefit extends to the oligoprogressive setting remains unclear. We present our institutional series of patients with oligometastatic or oligoprogressive malignancy treated with SBRT. MATERIALS/METHODS: We performed a retrospective study of patients with oligometastatic and oligoprogressive malignancy treated with SBRT between 2014 and 2019. Oligometastatic patients were defined as those with five or fewer metastatic lesions in total. Oligoprogressive patients were defined as those with more than five and up to twenty metastatic lesions in total, of which five or fewer metastases were progressing on current systemic therapy. Patients lacking complete treatment records or follow-up imaging were excluded. The study was approved by the NYU Institutional Review Board.
RESULT(S): A total of 114 patients were treated with 123 courses of SBRT, of which 96 treated oligometastasis and 27 treated oligoprogression. Primary sites of disease included lung (38%), prostate (20%), and GI (12%), as well as gynecologic, abdominal, and cutaneous malignancies. Median follow-up was 21 months. No grade 3 or higher radiation-related adverse events were reported. Patients with oligometastatic malignancy had longer 2-year overall survival (79% vs 59%; P=0.003), local control (73% vs 55%; P=0.01), and progression-free survival (26% vs 8%; P < 0.001), but similar freedom from new systemic therapy (36% vs 31%; P=0.8). This result held true in subgroup analysis regardless of lung vs non-lung primary site, and regardless of the presence or absence of a targetable mutation.
CONCLUSION(S): In this hypothesis-generating retrospective cohort study, patients with oligoprogressive malignancy treated with SBRT have similar freedom from new systemic therapy to patients with oligometastatic malignancy, strengthening the rationale for treating oligoprogressive malignancy with SBRT.
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