Prostate Cancer Recurrence: Examining the Role of Salvage Radiotherapy Field and Risk Factors for Regional Disease Recurrence Captured on 18F-DCFPyL PET/CT.

PURPOSE: The role of elective pelvic nodal irradiation in salvage radiotherapy (sRT) remains controversial. Utilizing 18F-DCFPyL PET/CT, this study aimed to investigate differences in disease distribution after whole pelvic (WPRT) or prostate bed (PBRT) radiotherapy and to identify risk factors for pelvic lymph node (LN) relapse. METHODS: This retrospective study included patients with PSA > 0.1 ng/mL post-radical prostatectomy (RP) or post-RP and sRT who underwent 18F-DCFPyL PET/CT. Disease distribution on 18F-DCFPyL PET/CT after sRT was compared using Chi-square tests. Risk factors were tested for association with pelvic LN relapse after RP and salvage PBRT using logistic regression. RESULTS: 979 18F-DCFPyL PET/CTs performed at our institution between 1/1/2022 - 3/24/2023 were analyzed. There were 246 patients meeting criteria, of which 84 received salvage RT after RP (post-salvage RT group) and 162 received only RP (post-RP group). Salvage PBRT patients (n = 58) had frequent pelvic nodal (53.6%) and nodal-only (42.6%) relapse. Salvage WPRT patients (n = 26) had comparatively lower rates of pelvic nodal (16.7%, p = 0.002) and nodal-only (19.2%, p = 0.04) relapse. The proportion of distant metastases did not differ between the two groups. Multiple patient characteristics, including ISUP grade and seminal vesicle invasion, were associated with pelvic LN disease in the post-RP group. CONCLUSION: At PSA persistence or progression, salvage WPRT resulted in lower rates of nodal involvement than salvage PBRT, but did not reduce distant metastases. Certain risk factors increase the likelihood of pelvic LN relapse after RP and can help inform salvage RT field selection.

Utilization and Factors Precluding Receipt of Checkpoint Inhibitor Consolidation for Stage III NSCLC in a Large US Academic Health System.

OBJECTIVES: We sought to determine the proportion of patients with stage III non-small cell lung cancer (NSCLC) who initiate consolidation durvalumab or other immune checkpoint inhibitors (ICIs) after concurrent chemoradiotherapy (cCRT), as well as reasons for nonreceipt and prognostic implications. MATERIALS AND METHODS: We retrospectively identified consecutive patients with unresectable stage III NSCLC treated with definitive cCRT between October 2017 and December 2021 within a large US academic health system. Patients either received consolidation ICIs (ICI group) or did not (no-ICI group). Baseline characteristics and overall survival (OS) of the groups were assessed. Factors predictive of ICI nonreceipt were evaluated using logistic regression. RESULTS: Of 333 patients who completed cCRT, 229 (69%) initiated consolidation ICIs; 104 (31%) did not. Reasons for ICI nonreceipt included progressive disease post-cCRT (N = 31, 9%), comorbidity or intercurrent illness (N = 25, 8%), cCRT toxicity (N = 23, 7%; 19/23 pneumonitis), and EGFR/ALK alteration (N = 14, 4%). The no-ICI group had worse performance status and a higher rate of baseline pulmonary comorbidity. Larger planning target volume was associated with post-cCRT progressive disease, and higher lung radiation dose with cCRT toxicity. Median OS was 16 months in the no-ICI group and 34.4 months in the ICI group. In the no-ICI group, OS was superior among those with EGFR/ALK alterations (median 44.5 months) and worst among those with progressive disease (median 5.9 months, P < 0.001). CONCLUSION: 31% of patients who completed cCRT for stage III NSCLC did not receive consolidation ICIs. Survival amongst these patients is poor, especially for those with progressive disease post-cCRT.

Long-term outcomes of a prospective randomized trial of 131Cs/125I permanent prostate brachytherapy.

PURPOSE: Iodine-125 (125I) is the most commonly used isotope for prostate brachytherapy (BT). Cesium-131 (131Cs) has a higher dose rate and shorter dose delivery time resulting in decreased duration of acute urinary morbidity. Long-term data suggest excellent oncologic outcomes; it is not known how outcomes compare. A prospective randomized trial comparing the two isotopes was initiated. MATERIALS AND METHODS: Patients with low- or intermediate-risk disease were treated with a BT in a single outpatient facility. Prescription dose was 144 Gy for 125I and 115 Gy for 131Cs. Androgen deprivation or supplemental EBRT was not allowed. The primary study objective was comparison of the mean EPIC Urinary Domain Score. Secondary objective was biochemical relapse-free survival (BRFS) comparison. Time-to-event for all outcomes of interest was measured from implant date. RESULTS: One hundred forty men were enrolled; 81.4% were low-risk and 18.6% were intermediate-risk. The median followup was 97 months. Urinary and sexual health-related quality of life did not differ between isotopes at any recorded time point. At 2 months after implantation, bowel health-related quality of life was worse with 125I; however, this difference was lost at subsequent time points. The 9-year BRFS was 87.2% and 84.0% for the 125I and 131Cs group, respectively (p = 0.897). There was no statistically significant difference in BRFS based on initial T stage, PSA, or Gleason score. CONCLUSIONS: Short- and long-term urinary, sexual, and bowel quality of life, as well as long-term biochemical control were comparable between 125I and 131Cs. This report therefore supports the continued use of 131Cs as an effective and comparable alternative isotope.

Safety practices and opportunities for improvement in brachytherapy: A patient safety practices survey of the American Brachytherapy Society membership.

PURPOSE: Safe delivery of brachytherapy and establishing a safety culture are critical in high-quality brachytherapy. The American Brachytherapy Society (ABS) Quality and Safety Committee surveyed members regarding brachytherapy services offered, safety practices during treatment, quality assurance procedures, and needs to develop safety and training materials. METHODS AND MATERIALS: A 22-item survey was sent to ABS membership in early 2019 to physicians, physicists, therapists, nurses, and administrators. Participation was voluntary. Responses were summarized with descriptive statistics and relative frequency distributions. RESULTS: There were 103 unique responses. Approximately one in three was attending physicians and one in three attending physicists. Most were in practice >10 years. A total of 94% and 50% performed gynecologic and prostate brachytherapy, respectively. Ninety-one percent performed two-identification patient verification before treatment. Eighty-six percent performed a time-out. Ninety-five percent had an incident reporting or learning system, but only 71% regularly reviewed incidents. Half reviewed safety practices within the last year. Twenty percent reported they were somewhat or not satisfied with department safety culture, but 92% of respondents were interested in improving safety culture. Most reported time, communication, and staffing as barriers to improving safety. Most respondents desired safety-oriented webinars, self-assessment modules, learning modules, or checklists endorsed by the ABS to improve safety practice. CONCLUSIONS: Most but not all practices use standards and quality assurance procedures in line with society recommendations. There is a need to heighten safety culture at many departments and to shift resources (e.g., time or staffing) to improve safety practice. There is a desire for society guidance to improve brachytherapy safety practices. This is the first survey to assess safety practice patterns among a national sample of radiation oncologists with expertise in brachytherapy.

Cardiac Monitoring for Thoracic Radiation Therapy: Survey of Practice Patterns in the United States.

OBJECTIVE: The American Society of Clinical Oncology (ASCO) 2017 guidelines on cardiac monitoring during cancer treatments identified patients receiving thoracic radiation (TRT) ≥30 Gy (heart in field) at increased risk for developing radiation-induced heart disease (RIHD). ASCO encouraged clinicians to actively screen and monitor for baseline modifiable cardiac risk factors and therapy-induced cardiotoxicity in this high-risk population. Coronary artery calcium (CAC) is an independent risk factor for adverse cardiac events that can be mitigated with preventative medical therapy. It is unclear whether radiation oncologists (ROs) are aware of ASCO guidelines or the implications of CAC observed on computed tomographic scans. We report on practice patterns, perceptions, and experiences of cardiac monitoring for patients receiving definitive TRT, excluding breast patients. MATERIALS AND METHODS: A 28-question survey was emailed to United States ROs 3 times from September 2018 to January 2019. RESULTS: There were 162 respondents from 42 states, 51% in academic practice. Most ROs (81%) were not aware of the ASCO guidelines. Only 24% agreed with the guidelines, only 27% believed symptomatic RIHD could manifest within 2 years of TRT, and 69% thought there was a lack of strong evidence for type and timing of cardiac monitoring tests. If CAC was evident on computed tomographic scans, 40% took no further action to inform the patient or referring doctor. CONCLUSIONS: This survey highlights a critical gap in knowledge about cardiac monitoring and potentially life-saving opportunities for preventive cardiac medical management. Future studies focusing on timing and detection of RIHD may elucidate the utility of cardiac monitoring for TRT patients.

Long-term biochemical outcomes using cesium-131 in prostate brachytherapy.

PURPOSE: Long-term outcomes reveal equivalent biochemical outcomes with low-dose-rate (LDR) brachytherapy (BT) compared with radical prostatectomy and external-beam radiotherapy for the management of prostate cancer. Iodine-125, the most commonly used isotope, may be associated with long-term urinary consequences. Cesium-131 (131Cs) has a higher dose rate and shorter dose delivery time, predicting a shorter duration of urinary morbidity. We report our institution's high-volume experience and the most mature data to date on outcomes with 131Cs prostate BT. METHODS AND MATERIALS: 571 men (median age: 65.38 years) with low (55%)-, intermediate (36%)-, and high-risk disease (9%) received monobrachytherapy, dual-modality, or trimodality using 131Cs at a single institution. Risk groups were defined according to the National Comprehensive Cancer Network definition. Median prescription dose for definitive LDR-BT and LDR-BT boost was 115 Gy and 70 Gy, respectively. Median initial PSA was 6.1 ng/mL (IQR: 4.6-8.7). RESULTS: Median followup time was 5 years. 5/7-year overall survival for low-, intermediate-, and high-risk patients was 96.9%/96/9%, 92.8%/89.7%, and 95.8%/87.1%, respectively (p = 0.02). 5/7-year freedom from biochemical failure for low-, intermediate-, and high-risk patients was 98.5%/96.3%, 94.1%/86.4%, and 93.2%/74.5%, respectively (p < 0.01). 5/7-year prostate cancer -specific survival was 100%/100%, 99.3%/99.3%, and 98.0%/98.0% for low-, intermediate-, and high-risk patients, respectively (p < 0.01). CONCLUSIONS: 131Cs is a viable alternative isotope for prostate brachytherapy for organ-confined disease. Long-term biochemical control and survival outcomes are excellent and on par with those attained with the use of 125I or 103Pd. This report therefore supports the continued use of 131Cs as an effective and comparable alternative isotope.

Concurrent Radiation and Immunotherapy: Survey of Practice Patterns in the United States.

OBJECTIVE: The objective of this study was to report on US radiation oncologists' (ROs) practice patterns and perceptions of concurrent radiation (RT) and immunotherapy (IT) (CRI). METHODS: A 22-question survey was emailed to radiation oncologists in February 2018. CRI was defined as RT completed within 1 week before initial IT infusion through 4 weeks after final IT infusion. RESULTS: Of the 323 respondents from 45 states, 88% had experience treating a patient with CRI, including 51% private and 48% academic physicians. The most common reason for not offering CRI was concerns of increased toxicity (50%). Although 84% to 94% of respondents did not change RT dose, more ROs decreased dose when treating central structures (chest/abdomen/pelvis) versus noncentral structures (brain/head and neck/extremities): 13% to 15% versus 4% to 8%, P<0.001. The majority (58% to 80%) of respondents would not delay RT from last IT infusion. Moderate and significant actual toxicities were rare (medical intervention 6%, hospitalization/death <1%). 97.5% of ROs did not routinely prescribed prophylactic steroids for CRI. More ROs believed CRI with SBRT/SRS versus palliative RT had better local control (35% vs. 25%, P<0.05) and higher rates of abscopal responses (41% vs. 25%, P<0.01). CONCLUSIONS: Despite concerns for toxicity, ROs with CRI experience reported minimal toxicities. Most ROs do not alter RT dose, use prophylactic steroids, or delay starting RT from last IT infusion. Uncertainty remains about improved local control outcomes and abscopal responses from CRI, with a perception that concurrent SBRT offers better outcomes than palliative RT. These survey results may help guide ROs until more definitive data are available.

Checkpoint Inhibition: Will Combination with Radiotherapy and Nanoparticle-Mediated Delivery Improve Efficacy?

Checkpoint inhibition (CPI) has been a rare success story in the field of cancer immunotherapy. Knowledge gleaned from preclinical studies and patients that do not respond to these therapies suggest that the presence of tumor-infiltrating lymphocytes and establishment of immunostimulatory conditions, prior to CPI treatment, are required for efficacy of CPI. To this end, radiation therapy (RT) has been shown to promote immunogenic cell-death-mediated tumor-antigen release, increase infiltration and cross-priming of T cells, and decreasing immunosuppressive milieu in the tumor microenvironment, hence allowing CPI to take effect. Preclinical and clinical studies evaluating the combination of RT with CPI have been shown to overcome the resistance to either therapy alone. Additionally, nanoparticle and liposome-mediated delivery of checkpoint inhibitors has been shown to overcome toxicities and improve therapeutic efficacy, providing a rationale for clinical investigations of nanoparticle, microparticle, and liposomal delivery of checkpoint inhibitors. In this review, we summarize the preclinical and clinical studies of combined RT and CPI therapies in various cancers, and review findings from studies that evaluated nanoparticle and liposomal delivery of checkpoint inhibitors for cancer treatments.

Multi-institutional report on toxicities of concurrent nivolumab and radiation therapy.

PURPOSE: Radiation therapy (RT) and nivolumab are standard therapies for a wide range of advanced and metastatic cancers, yet little is known about the toxicity profile of their combined treatment. The rate of grade ≥3 toxicities from nivolumab monotherapy and radiation-only palliative treatments has been reported at 10% to 18% and 0% to 26%, respectively. We reviewed our experience to assess the acute toxicity profile of concurrent RT-nivolumab. METHODS AND MATERIALS: A retrospective review of all consecutive patients from January 2015 to May 2017 who received concurrent RT-nivolumab was conducted at 4 separate centers. Concurrent RT-nivolumab was defined as RT completed between 3 days prior to initial nivolumab infusion and 28 days after the last nivolumab infusion. RESULTS: Of the 261 patients who received nivolumab, 46 (17.6%) had concurrent RT to 67 treatment sites. The median follow-up was 3.3 months (interquartile range, 1.7-6.1 months) and the 1-year overall survival rate was 22%. For the 11 of 46 patients (24%) who were alive at last analysis, the median follow-up was 12.8 months (interquartile range, 8.3-14.9 months). The most common histology, RT prescription, and treatment site were non-small cell lung cancer (23 of 46 patients; 50%), 30 Gy in 10 fractions (24 of 67 patients; 35.8%), and abdomen/pelvis (16 of 67 patients; 24%), respectively. Four patients with melanoma had concurrent ipilimumab and were removed from the final toxicity analysis of RT-nivolumab. Within 3 months of treatment with RT-nivolumab, 4 of 42 patients (9.5%) experienced grade 3 toxicity and 2 of these patients' toxicities were attributed specifically to the addition of RT: grade 3 hearing loss after whole brain RT and grade 3 pancreatitis after stereotactic body RT to the left adrenal gland. One death from transaminitis was attributed to nivolumab alone because the RT field did not encompass the liver. CONCLUSIONS: Concurrent RT-nivolumab did not appear to increase the toxicity profile from the previously reported toxicity rates from nivolumab or radiation alone.

Long-term outcomes analysis of low-dose-rate brachytherapy in clinically T3 high-risk prostate cancer.

PURPOSE: The available data demonstrating that superiority of LDR brachytherapy (LDR-BT) boost in high-risk prostate cancer patients under represents patients with extracapsular extension (T3a) and/or seminal vesicle invasion (T3b) have been limited. We report long-term clinical outcomes data for patients with cT3a/b disease receiving LDR-BT. METHODS AND MATERIALS: Ninety-nine men (median age: 69.4 years) with cT3a/bN0M0 high-risk prostate adenocarcinoma received definitive LDR-BT or LDR-BT boost after external beam radiation therapy (EBRT) at a single institution between 1998 and 2007. About 86% of patients received androgen deprivation therapy. Freedom from biochemical failure (FFBF), prostate cancer-specific survival (PCSS), and overall survival (OS) was calculated using the Kaplan-Meier method with the Phoenix definition used as definition of failure. Cox regression analysis was used to compare outcomes between clinical stage, initial PSA, Gleason Score, and percent core positive rate. RESULTS: With a median followup of 7 years, 7-year rate of FFBF, PCSS, and OS for the entire cohort was 65.2% (±5.6%), 90.1% (±3.6%), and 77.9% (±4.7%), respectively. LDR-BT boost patients achieved a 7-year FFBF rate of 73.5 (±6.5%). No significant difference in outcomes was present between T3a or T3b disease, Gleason score, iPSA stratification and percent core positive rates. CONCLUSIONS: LDR-BT, primarily as a boost in conjunction with ADT and EBRT, is not only feasible, but also highly effective in men with cT3a and cT3b high-risk prostate cancer resulting in excellent biochemical control and survival outcomes. LDR-BT boost implantation of patients should be strongly considered for cT3 patients given the merits of trimodality care.

Hypofractionated Palliative Radiotherapy with Concurrent Radiosensitizing Chemotherapy for Advanced Head and Neck Cancer Using the "QUAD-SHOT Regimen".

AIM: To analyze the outcomes using the hypofractionated palliative radiotherapy regimen "QUAD-Shot" with concurrent radiosensitizing chemotherapy for advanced head and neck cancer. MATERIALS AND METHODS: We analyzed twenty-one patients with newly-diagnosed or recurrent head and neck cancer treated with palliative hypofractionated concurrent chemoradiation using the QUAD-Shot regimen. RESULTS: All patients received at least one cycle of RT, with sixteen patients (76%) completing all three cycles. 85.7 % of patients had objective response to therapy with five patients (23.8%) demonstrating complete response (CR) and thirteen patients (61.9%) demonstrating partial response (PR). Palliation of symptoms was achieved in all (100%) of the sixteen patients that completed the three cycles. Median overall survival and median progression-free survival were 7 and 4 months, respectively. CONCLUSION: QUAD-Shot palliative radiation therapy coupled with radiosensitizing chemotherapy is efficacious and well-tolerated in patients with newly-diagnosed or recurrent head and neck cancer not amenable to curative therapy.

Impact of the use of an endorectal balloon on rectal dosimetry during stereotactic body radiation therapy for localized prostate cancer.

PURPOSE: Endorectal balloons may be of benefit during stereotactic body radiation therapy of the prostate to limit intrafraction prostatic motion and potentially minimize rectal toxicity. We evaluated the effect of the endorectal balloon (ERB) on rectal dosimetry, specifically the absolute volume of rectum receiving high dose. METHODS AND MATERIALS: Eleven patients with localized prostate cancer underwent stereotactic body radiation therapy planning with computed tomography simulation with and without a RadiaDyne ERB inflated with 60 mL of water. Prescription dose was 3625 cGy in 5 fractions of 725 cGy. The V3600 (volume receiving 3600 cGy), V3440 (volume receiving 3440 cGy), and volume receiving 50% of the prescription dose were calculated for both the rectum and rectal wall. Repeat plans were generated using smaller planning target volume margins (reduced to 1 mm from 3 mm posteriorly) and after virtually replacing the water-filled ERB with air equivalent density. Comparisons were made using the Wilcoxon signed-rank test. RESULTS: The rectal V3600 and V3440 were significantly lower without ERB than with water-filled ERB using standard 3-mm posterior margin (P = .003 for both V3600/V3440), water-filled ERB using reduced 1-mm posterior margin (P = .016 and .003), or air-filled ERB (P = .003 and .004). Regarding the rectal wall, V3600 and V3440 were also significantly lower without ERB than with any ERB, except when using the water-filled ERB with reduced posterior margin (P = .328). The volumes of rectum and rectal wall receiving lower dose (volume receiving 50% of the prescription dose) were not significantly greater without the ERB. CONCLUSION: We found an increase in the volume of rectum and rectal wall receiving high dose radiation utilizing an ERB. Consideration in using an ERB should account for potential increased rectal dose and subsequent toxicity.

Dose-escalated radiation therapy with and without short-course androgen deprivation for intermediate-risk prostate cancer.

AIM: To investigate outcomes in intermediate-risk (IR) prostate cancer patients receiving dose-escalated external beam radiation therapy (RT) with or without short-course androgen deprivation (ADT). PATIENTS AND METHODS: This study comprised of 203 patients with IR prostate cancer who were treated at a single institution to a dose of 7,560 cGy or more between 2003-2010. Of these, 62 (30.5%) patients received ADT. Biochemical recurrence, distant metastatic-free survival, prostate cancer-specific survival, and overall survival were analyzed using the Kaplan-Meier method. RESULTS: The median follow-up was 62 months and the median duration of ADT was 6 months. The 6-year biochemical control was 89.2% for those receiving RT plus ADT versus 76.7% in those receiving RT alone (p=0.02). There were no differences between the two groups regarding distant metastatic-free survival, prostate cancer-specific survival, and overall survival (respective p-values of 0.91, 0.50, 0.67). CONCLUSION: Dose-escalated RT and short-course ADT results in improved biochemical outcomes for IR prostate cancer.

Concordance Between Prostate Needle Biopsy and Surgical Histopathology in a Primarily African-American Population.

INTRODUCTION: Prior studies have revealed that the concordance between biopsy and surgical specimens has been improving over time. However, to date, this has not been analyzed in an African American population, for whom data have often shown more aggressive prostate cancer than for other races. METHODS: We analyzed 250 patients who were operated on at the NY Harbor Department of Veterans Affairs for localized prostate cancer between 2003 and 2010. The clinical biopsy scores were compared with the pathological biopsy scores. We compared the concordance using the κ coefficient. Univariate and multivariate logistic regressions were used to identify predictors for poor concordance. RESULTS: This population consisted of 59.6% African Americans, 32% Caucasians, and 8.4% Hispanics. Overall, there was a 50% exact concordance between the biopsy and surgical specimens. The κ was 0.33, indicating fair agreement. Patients with a Gleason score of 6 were found to have an exact concordance 66% of the time, and those with a score of Gleason 7 (3 + 4) had an exact concordance 50% of the time. On univariate and multivariate analyses, only an increasing prostate-specific antigen was associated with reduced concordance. Race was not a significant predictor. CONCLUSIONS: These data are in line with prior studies of concordance. Despite being a population with more aggressive prostate cancer, there does not appear to be an increase in the risk of discordance in African American men.