Received Salvage Radiotherapy Research Articles

Efficacy of salvage surgery versus re-irradiation for isolated regional lymph node recurrence in patients with nasopharyngeal carcinoma

BackgroundTo compare the clinical characteristics and prognoses of patients with isolated regional lymph node recurrent nasopharyngeal carcinoma (irrNPC) who underwent surgery or re-irradiation treatment.MethodsWe retrospectively reviewed 124 irrNPC patients who underwent initial radiotherapy between January 2010 and December 2020. The staging of regional lymph node recurrence was as follows: 75.8% for rN1, 14.5% for rN2, and 9.7% for rN3. Fifty-five patients underwent regional lymph node surgery (Surgery group), and sixty-nine patients received salvage radiotherapy with or without chemotherapy (Re-irradiation group). The survival rate was compared using Kaplan‒Meier analysis and evaluated by the log-rank test. Cox proportional hazard models were used to analyze prognostic factors.ResultsThe median follow-up time was 70 months, the 5-year overall survival (OS) was 74%, and the median survival time was 60.8 months. There were no significant differences in 5-year OS (75.6% vs. 72.4%, P = 0.973), regional recurrence-free survival (RRFS, 62.7% vs. 71.1%, P = 0.330) or distant metastasis-free survival (DMFS, 4.2% vs.78.7%, P = 0.677) between the Surgery group and Re-irradiation group. Multivariate analysis revealed age at recurrence, radiologic extra-nodal extension (rENE) status, and recurrent lymph node (rN) classification as independent prognostic factors for OS. The rENE status was an independent prognostic factor for DMFS. Subgroup analysis of the Surgery group revealed that the rN3 classification was an adverse prognostic factor for OS. Age at recurrence ≥ 50 years, GTV-N dose, and induction chemotherapy were found to be independent prognostic factors for OS, RRFS, and DMFS, respectively, in the Re-irradiation group.ConclusionsFor NPC patients with isolated regional lymph node recurrence after initial radiotherapy, those who underwent surgery had survival prognosis similar to those who underwent re-radiotherapy with or without chemotherapy. A prospective study is needed to validate these findings.

Unraveling the Mystery of Desmoid Tumors: Insights From a Moroccan Tertiary Center.

Desmoid tumors (DTs) are rare, aggressive malignancies developing from clonal fibroblastic proliferation originating from soft tissues. Despite their low metastatic potential, their invasiveness towards neighboring organs and a high recurrence rate contribute significantly to morbidity and mortality, thereby impacting the quality of life of patients. Several therapeutic options are available, but standardized protocols are lacking. In this study, we reviewed 14 cases of DT retrospectively over a period of 15 years, from September 2008 to December 2023. The most prevalent tumor locations were in the extremities, and the majority of patients were female. We identified risk factors in two patients, those being surgical trauma and familial adenomatous polyposis (FAP). Half of the patients underwent surgery for DT, and two received salvage radiotherapy. Systemic therapy was used in the first and second lines and comprised of chemotherapy, endocrine therapy, and non-steroidal anti-inflammatory drugs (NSAI). Active surveillance was proposed in three patients. This is the first retrospective study to assess the characteristics of DT in Moroccan patients in a tertiary care setting. It aims to shed light on the challenges faced in treating these rare tumors in the context of a lack of therapeutic standardization.

Does a patient-specific bladder-filling protocol affect bladder volume and dose in postprostatectomy radiotherapy?

Our aim is to develop a patient-specific bladder-filling protocol (PSP) using an ultrasound-based bladder scanner (BS) and compare the volumetric and dosimetric parameters with those of the standard filling protocol (SP) in postprostatectomy patients. Twenty postprostatectomy patients who received salvage radiotherapy (72Gy/36 fx) were included. For PSP, the patient was asked to drink 500mL of water after emptying his bladder. Bladder volume was measured using BS every 10min. Each patient's unique time to reach a 150-200cc volume was used for simulation and treatment. For the SP, the patient was asked about the feeling of having a full bladder. Organs at risk (OAR) were contoured on cone-beam computed tomography (CBCT) scans that were transferred to the treatment planning system (TPS). Treatment plans were applied to CBCTs. Changes in bladder volume and doses for planning computed tomography (PCT) and CBCT were determined. In the SP, there was no significant difference in mean bladder volume for PCT and CBCT (p = 0.139); however, there was a trend for significance in the mean bladder dose (p = 0.074). In PSP, there was no significant difference in the mean bladder volume or dose for PCT and CBCT (p = 0.139 and p = 0.799, respectively). There was a significant difference in terms of mean CBCT bladder volume between the two protocols (p = 0.007), whereas no significant difference was detected in terms of bladder dose (p = 0.130). With PSP, optimal bladder filling was obtained and maintained throughout the whole treatment course, and it was reproducible in every fraction.

Study of prostate-specific antigen levels during salvage radiotherapy after prostate cancer surgery

BackgroundAdministration of adjuvant or salvage radiotherapy (RT) after prostate cancer (PCa) surgery is supported by clinical evidence and is a widely adopted strategy. On occasion, we detect changes in prostate-specific antigen (PSA) levels, such as a transient elevation or decline, during RT. Thus, we retrospectively investigated the frequency of changes in PSA levels, their associations with histopathological parameters, PSA doubling time (PSADT), and biochemical recurrence (BR) of PCa.MethodsThis study included 23 consecutive patients who underwent surgery for PCa between 2012 and 2019, received salvage RT without hormone therapy, and exhibited changes in PSA levels during RT. The prostatic bed was irradiated with a total dose of 64 to 66 Gy. BR was defined as consecutive PSA levels exceeding 0.2 ng/mL or having to start hormone therapy because of PSA elevation after salvage RT.ResultsDuring salvage RT after PCa surgery, PSA levels transiently increased in 11 patients (47.8%) and decreased in 12 (52.2%). When factors associated with BR were examined in patients with transient PSA elevation, seminal vesicle invasion and preoperative PSA values were identified as being statistically significant. When factors for BR were examined in patients with a decline in PSA levels, the Gleason score and PSADT were identified as being significant. Among the cases of a decline in PSA levels during salvage RT, those who received a radiation dose of less than 36 Gy did not experience BR. Similarly, patients who exhibited changes in PSA levels during salvage RT and did not have perineural invasion did not experience BR.ConclusionThis is the first study to examine the histopathological factors possibly affecting BR in patients undergoing salvage RT after PCa surgery. The results indicate that in patients with transient PSA elevation, seminal vesicle invasion is a significant risk factor. On the other hand, in patients with a decline in PSA levels during irradiation, the Gleason score and perineural invasion were found to be potential risk factors for BR. These findings suggest that a thorough examination of postoperative histopathological results may be necessary for the optimal management of patients with PCa.

Outcomes of Bridging and Salvage Radiotherapy in Relapsed or Refractory Mantle Cell Lymphoma Patients Undergoing CD19-Targeted CAR T-Cell Therapy.

We sought to describe our early experience of using bridging and salvage radiation therapy (RT) in patients with relapsed/refractory mantle cell lymphoma (MCL) undergoing CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. A retrospective study was conducted for consecutive MCL patients who were treated with commercially available CD19-targeted CAR T-cell therapy between 2020 and 2022 at a single institution. Patients who received RT pre-and post-CAR T-cell therapy were identified and analyzed using descriptive and statistical analysis. Overall survival (OS) from the date of CAR T infusion was estimated with the Kaplan-Meier method. The duration of local control (LC) was defined as the time between the start date of RT and the date of in-field progression/relapse. Response to RT was analyzed based on the total number of irradiated sites. A total of 21 patients with MCL who received CD19-targeted CAR T-cell therapy were identified (17 brexu cel, 3 tisa-cel, and 1 liso-cel) with a median follow-up of 15.3 months (24 days-36.2 months). The median age was 65 years at time of apheresis (43-83 years). The median OS for the entire cohort following CAR T-cell therapy was 17 months (95% CI: 14.2 months-not reached). Of the 21 patients, 1 patient received bridging RT prior to CAR T infusion, 1 patient received RT pre-and post-CAR T, and 5 patients received salvage RT post-CAR T with a total of 23 irradiated sites. Sites of RT include: extremities (10), central nervous system (3), pelvis/groin (3), head and neck (3), chest (2), abdomen (1), and multiple sites (1). The median dose/fractionation were 16.5 Gy (range, 3.6-45 Gy) and 5.5 fractions (range, 2-16 fractions)- radiation data was incomplete only for 1 patient who received RT at an outside institution. The in-field responses of the 21 evaluable sites were as follows: complete response (CR) (n = 18, 86%) and partial response (PR) (n = 3, 14%), translating into an LC rate of 100%; the remaining 2 sites were not evaluable since the patient died shortly after receiving RT due to progressive lymphoma. Notably, there was no correlation between RT dose and LC; 9 sites received low-dose RT (3.6-6 Gy) with responses as follows: CR (n = 6, 67%) and PR (n = 3, 33%). Only 1 patient experienced grade 3-4 RT-related toxicities. At the time of the last follow-up, 4 patients remained alive, and 3 patients succumbed to progressive lymphoma. As no studies exclusively focusing on CAR T-cell therapy and bridging or salvage RT have been published among relapsed/refractory MCL patients, our early experience underlines that using RT as a bridging and salvage approach is associated with excellent in-field control and limited toxicity in the peri-CAR T setting. Low-dose RT for MCL appears to be very effective in this highly refractory population and warrants further investigation.

Radiation therapy as a bridging and salvage strategy in patients with relapsed or refractory multiple myeloma undergoing BCMA-targeted CAR T-cell therapy

Radiation therapy (RT) may play an important role prior to and following BCMA-targeted CAR T-cell therapy in multiple myeloma (MM). We report a series of 13 patients: 5 patients received bridging RT pre-CAR T, 4 patients received salvage RT post-CAR T failure, and 4 patients received both. There was no worsening of CAR-T- or RT-related toxicities. The RT in-field local control rate was 100%, with a median follow-up after each RT course of 7.3 months. RT as a bridging and salvage strategy is safe, feasible, and offers excellent local control in MM patients treated with CAR T-cell therapy.

Adjuvant Radiotherapy in Atypical Meningioma: Are the Risks Worth the Benefit?

Adjuvant radiotherapy (RT) improves progression-free survival (PFS) in atypical meningiomas. Herein, we assess whether the treatment-related acute and long-term toxicity of upfront RT in atypical meningioma patients versus surveillance merits the PFS benefit. In our prior single institution retrospective study of 230 patients with resected intracranial atypical meningiomas between 2000-2015, adjuvant RT was associated with a significantly lower risk of progression/recurrence compared to surveillance (HR = 0.21 [95% CI 0.11-0.41]; p<0.01), with 36% of surveillance patients eventually requiring salvage RT. In the current study, the acute (≤6 months) and long term (>6 months) RT-related toxicities from the same patient cohort for those who received adjuvant RT (n = 51) were evaluated and compared to those who received salvage RT (n = 64) in the surveillance group. Additionally, overall treatment-related toxicity at time of last follow up was obtained for comparison between the adjuvant RT (n = 51) vs surveillance (n = 179) group. All toxicities were graded per CTCAE v5.0. Kaplan-Meier analysis was used to calculate the cumulative incidence of toxicities; Pearson's chi-squared and log-rank test were used for comparison. Adjuvant RT as compared to salvage RT was generally associated with greater RT-related toxicities both in the acute (90% vs 69%, p = 0.006) and long term (57% vs 33%, p = 0.010). While there was no significant difference in grade 3-4 acute toxicities, long term grade 3-4 toxicities (including headache, seizure, vision loss, neuromotor deficit, and neurocognitive deficit) were present in 14% of adjuvant vs 3% of salvage RT group (p = 0.035). Radionecrosis occurred in 18% of adjuvant RT vs 8% of salvage RT group (p = 0.11). Between adjuvant RT vs surveillance groups, any-treatment related toxicity at last follow up was greater with adjuvant RT (31% vs 15%; p = 0.006), with trend towards greater grade 3-4 toxicities (including headache, vision loss, neuromotor deficit, neurocognitive deficit, and cerebral edema) as well (8% vs 3%; p = 0.101). Cumulative incidence of treatment-related neuromotor deficit (any grade) was significantly greater in the adjuvant RT vs surveillance group with 14% vs 2% at 10 years (p = 0.004). There was no difference in rate of cerebrovascular accident between adjuvant RT (6%) vs surveillance (4%) groups (p = 0.83). Adjuvant RT for patients with atypical meningioma was associated with greater acute and long-term treatment toxicities. Potential RT-related toxicity and impact on quality-of-life should thus be carefully weighed against the tumor control benefit of RT in deciding the optimal use and timing of RT.

High-Intensity Focused Ultrasound (Sonablate®) for Prostate Cancer: Preliminary Outcomes in Taiwan.

We reported preliminary outcomes of high-intensity focused ultrasound (HIFU) [Sonablate®] in the combination of transurethral resection of the prostate for localized prostate cancer in Taiwan. Seventy-seven patients using Sonablate® HIFU for localized prostate cancer were enrolled in this study from April 2021 to December 2022. Prostate-specific antigen biochemical recurrence, International Index of Erectile Function (IIEF)-5 scores, International Prostate Symptom Score (IPSS), quality of life (QoL) scores, and postoperative complications were recorded during follow-up. Overall, 19.5% of patients were low-risk, 36.4% were intermediate-risk, and 44.1% were high-risk according to the D'Amico risk classification. The median follow-up was 12.09±5.85 months, and the biochemical-free survival rates for the low-, intermediate-, and high-risk groups were 100% (15/15), 96.4% (27/28), and 79.4% (27/34), respectively. Four patients (5.2%) received salvage radiotherapy and all maintained biochemical-free survival. The mean IPSS and QoL scores before versus after HIFU were 10.4 versus 6.8 (p=0.003) and 3.2 versus 3.0 (p=0.096), respectively. There was no statistically significant change in preoperative and postoperative IIEF scores (20.6 vs. 19; p=0.062) in patients who had an IIEF score of >15 at baseline and received nerve-sparing procedures (subtotal ablation). The results of Sonablate® HIFU in Taiwan indicated adequate short-term cancer control, excellent potency, and continence preservation. HIFU can achieve improvement of IPSS with low complication rates.

Radiotherapy for postoperative vaginal recurrences of cervical squamous cell carcinoma: analysis of dosing and prognosis

Squamous cell carcinoma (SCC) is the most common type of vaginal recurrence in cervical cancer patients, and the role of salvage radiotherapy on these patients remains unclear. This study aimed to investigate the efficacy of salvage radiotherapy for vaginal recurrence of SCC in patients who previously underwent surgery and to explore prognostic factors associated with survival. Ninety-seven patients with histologically proven SCC who were treated for vaginal recurrence at Peking Union Medical College Hospital were identified. All patients had previously undergone surgery and received salvage radiotherapy. Factors predictive of overall survival (OS), progression-free survival (PFS), and local control (LC) were investigated. The median follow-up time was 42.5 months. The estimated 5-year OS, PFS, and LC rates were 84%, 79%, and 91%. On multivariate analysis, inguinal lymph node metastasis was significantly associated with poor OS; a tumour size ≤4 cm was associated with longer PFS (p < 0.05); the recurrence pattern was an independent predictor of LC (p < 0.05). In the 45 patients with recurrences that were paravaginal or invasive of surrounding organs, biologically equivalent doses in 2 Gy fractions of ≥72.6 Gy were independently predictive of longer LC (p < 0.05). RT is an effective treatment for postoperative vaginal recurrence in patients with cervical SCC. For patients with extravaginal recurrence, a salvage dose of ≥72.6 Gy appears to be optimal. Impact statement What is already known on this subject? Radiotherapy plays a critical role in treating recurrent cervical cancer, but the effectiveness of RT for vaginal recurrence in patients who previously underwent surgery remains limited. Few studies have focussed on the effect of RT dose on patient survival. What do the results of this study add? This study investigated the efficacy of RT in patients with cervical squamous cell carcinoma who experienced postoperative recurrence. Lymph node metastasis, tumour size and recurrence pattern were significantly associated with survival. Moreover, an EQD2 ≥ 72.6 Gy was independently predictive of longer LC. What are the implications of these findings for clinical practice and/or further research? RT is an effective treatment for postoperative vaginal recurrence in patients with cervical squamous cell carcinoma. For patients with extravaginal recurrence, a salvage dose of ≥72.6 Gy appears to be optimal.

RADIATION THERAPY AS A BRIDGING AND SALVAGE STRATEGY IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA UNDERGOING BCMA‐TARGETED CAR T‐CELL THERAPY

Introduction: Radiation therapy (RT) may be a useful bridging and/or salvage approach prior to and following B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed or refractory multiple myeloma (MM). Thus, we sought to report our early experience evaluating the potential role of RT in bridging and salvage settings in MM patients undergoing CAR T-cell therapy. Methods: A multi-institutional retrospective study was conducted for consecutive MM patients who received CAR T-cell therapy between 2018 and 2022. Patients who were administered bridging RT pre-CAR T and salvage RT post-CAR T failure were identified and analyzed using descriptive and statistical analysis. Results: We retrospectively reviewed 13 patients who have been treated with RT pre- and/or post-CAR T-cell therapy infusion at two tertiary care centers [5 patients received bridging RT pre-CAR T, 4 patients received salvage RT post-CAR T failure, and 4 patients received both bridging and salvage RT]. A total of 17 sites were treated with bridging-RT with a median dose of 20 Gy (range, 4–24 Gy) and a median of 5 fractions (range, 1–12 fractions). Twelve sites were treated with salvage RT with a median dose/fractionation of 20 Gy (range, 4–30 Gy) and 5 fractions (range, 1–12 fractions). No worsening in CAR T-related toxicities occurred among the patients who were treated with bridging RT, and no significant RT-related toxicities were observed post-bridging or salvage RT. For the entire cohort, the median overall survival was 16.2 months (95% CI: 8.6 months-not reached), and the median progression-free survival was 4.1 months (95% CI: 1.07 months-not reached). The local control rate for patients receiving bridging RT and/or salvage RT was 100%, with a median follow-up after each RT course of 7.3 months. Conclusion: Our findings suggest that using RT as a bridging and salvage strategy is safe and feasible, and offers excellent local control among relapsed/refractory MM patients treated with CAR T-cell therapy infusion. Future larger studies with translational correlatives are required to assess the optimal role of RT in these settings. Keywords: Cellular therapies, Multiple Myeloma No conflicts of interests pertinent to the abstract.

Phase 2 study of olaparib (without ADT) in men with biochemically recurrent prostate cancer (BCR) after prostatectomy.

5087 Background: The natural history of BCR after prostatectomy is variable and current treatment approaches include observation, salvage radiation, or androgen deprivation therapy (ADT), although many men wish to defer such therapy. We hypothesized that olaparib, now approved for use in certain men with metastatic castration resistant prostate cancer, might be an alternative option for men with high-risk BCR. Methods: This was a single arm, phase 2 trial (NCT03047135) conducted at 4 US sites. Subjects with biochemically recurrent (M0) prostate cancer, post prostatectomy, with a PSA doubling time of ≤6 months and an absolute PSA of ≥1.0 ng/mL were eligible. Patients were NOT selected based on the presence of homologous recombination repair (HRR) mutations. 51 patients were treated with olaparib 300mg twice per day, until radiographic or symptomatic progression, PSA doubling from baseline value, or drug-related toxicity. The primary endpoint was PSA50 response (50% PSA decline from baseline). Secondary endpoint was PSA progression free survival (PFS). Patients were required to undergo tissue-based next generation sequencing on the radical prostatectomy specimen to determine the presence of mutations in HRR genes ( ATM, BARD1, BRCA1/2, BRIP1, CDK12, CHEK1/2, FANCA/E/L, PALB2, RAD51B/C/D). A prespecified endpoint was to assess PSA responses in HRR[+] and HRR[–] cohorts separately. Results: Mean age was 64 years (SD 7), and 92% (47/51) of patients were White. Mean baseline PSA doubling time was 2.9 (SD 1.5) months. 55% (28/51) of pts had Gleason 6-7, 14% (7/51) had Gleason 8, and 31% (16/51) had Gleason 9-10. 86% (44/51) of patients had previously received salvage radiation. 27 patients harbored HRR mutations, the most common of which were BRCA2 (n=11), CHEK2 (n=6), and ATM (n=6). The overall PSA50 response rate was 24% (12 of 51)(95% CI 0.13, 0.38), with no responses in the HRR[–] group and 44% (12/27) PSA50 responses in the HRR[+] group (95%CI 0.26, 0.65). All 11 of the participants with a BRCA2 mutation achieved a PSA50 response. The median PSA PFS was 22 months in the HRR[+] group and 13 months in the HRR[–] group (HR 0.71; 95% CI 0.31, 1.63). Most AEs were low grade. The most common all-grade AEs were fatigue, nausea, leukopenia, anemia, and dysgeusia. Grade-3 AEs were leukopenia (9.8%), ALT/AST increase (3.9%), and anemia (2.0%). There were no grade 4–5 AEs. Conclusions: Olaparib, in the absence of ADT, can be safely administered and demonstrated activity in men with BCR prostate cancer and HRR mutations, especially for BRCA2 mutations. Additional studies to further evaluate olaparib in these patients are indicated. Clinical trial information: NCT03047135 .

18F-DCFPyL PSMA-PET affects management of salvage radiotherapy for post-prostatectomy patients with biochemical failure: A matched cohort study.

Our objective was to assess the effect of 18F-DCFPyL prostate-specific membrane antigen (PSMA) positron emission tomography (PET) on the management and outcomes of patients receiving salvage radiotherapy following biochemical failure (BF) post-radical prostatectomy (RP) using a matched cohort analysis. A PSMA-PET cohort of patients with BF post-RP was identified through a prospective registry. Patients from this registry were included if they did not have disease outside of the pelvis and underwent salvage radiotherapy to the prostate and/or pelvis. Case-control matching was performed with a contemporary cohort of patients with BF post-RP without PSMA-PET information. Forty-four patients were included in the PSMA-PET cohort and 80 were analyzed in the non-PSMA-PET cohort. The PSMA-PET cohort had a significantly higher pre-radiotherapy median prostate-specific antigen (PSA) of 0.48 ng/mL compared to 0.20 ng/mL in the non-PSMA-PET cohort (p<0.001), but these levels were similar after matching. The PSMA-PET cohort had a higher proportion of patients receiving radiotherapy to pelvic lymph nodes (n=27 [61.4%] vs. n=16 [20.0%], p<0.001). Median followup was 26 months (interquartile range 18.8-33) for both cohorts. BF-free survival and event-free survival were not significantly different between the two cohorts for all (p=0.662 and >0.99) and matched patients (p=0.808 and 0.808), respectively. Metastasis-free survival was significantly higher in the matched PSMA-PET cohort compared to the matched non-PSMA-PET cohort (p=0.046), although a higher proportion of patients in the non-PSMA-PET cohort underwent PSMA-PET restaging after BF (52% vs. 20%, p=0.08726). Our study showed that patients undergoing PSMA-PET scans after BF post-RP had a higher likelihood of pelvic nodal treatment at the time of salvage RT. Despite higher PSA levels at salvage, we identified no recurrence or survival differences.

MP40-14 ARE EAU RISK GROUPS RELIABLE IN THE STRATIFICATION OF MEN WITH BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY AND RESTAGED WITH PSMA-PET?

MP40-14 ARE EAU RISK GROUPS RELIABLE IN THE STRATIFICATION OF MEN WITH BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY AND RESTAGED WITH PSMA-PET?

Strategy for PSA progression in patients undergoing salvage radiation for biochemical recurrence after radical prostatectomy.

The treatment strategy for prostate-specific antigen (PSA) progression in patients who receive salvage radiation therapy (RT) for biochemical recurrence (BCR) after radical prostatectomy (RP) is salvage androgen deprivation therapy (ADT). However, its optimal timing is highly controversial. The study sample consisted of 77 men who underwent RP, received salvage RT against BCR, and underwent salvage ADT for PSA progression. The endpoint of this study was development to castration-resistant prostate cancer (CRPC), from the start of salvage RT. Themedian follow-uptime was 9.5years, and 20 patients experienced CRPC. The multivariable analysis identified PSA-doubling time (PSA-DT) ≤ 12months (hazard ratio, 3.5) and seminal vesicle invasion (SVI) (hazard ratio, 4.4) as independent risk factors. We defined the high-risk and low-risk groups as those with one or two risk factors and no risk factors, respectively. In the high-risk group, a significant difference in time to CRPC was observed between patients who received salvage ADT at PSA ≤ 1.0ng/mL (n = 8) and at > 1.0ng/mL (n = 27) (10-year non-CRPC rate: 100.0% vs. 46.3%, respectively). In contrast, in the low-risk group, no significant difference in CRPC-free survival was observed between patients who received salvage ADT at PSA ≤ 1.0ng/mL (n = 14) and at > 1.0ng/mL (n = 28) (10-year non-CRPC rate: 86.4% vs. 80.8%, respectively). In high-risk patients (PSA-DT ≤ 12months and/or SVI), salvage ADT for PSA progression after salvage RT should be started before the PSA levels exceed 1.0ng/mL.

Potential synergy between radiotherapy and CAR T-cells - a multicentric analysis of the role of radiotherapy in the combination of CAR T cell therapy

BackgroundChimeric antigen receptor (CAR) T-cell therapy has improved the limited overall survival (OS) of patients with intensively pretreated diffuse large B-cell lymphoma (DLBCL). However, the potentially life-threatening toxicities of CAR T-cells and early relapses remain a challenge. As suggested by smaller monocentric analyses, radiotherapy (RT) in combination with CAR T-cells may have an immunomodulatory effect. Method/ ResultsIn this multicentric retrospective analysis, we investigated potentially synergistic effects of RT and CAR T-cells. Of 78 patients from four centers who received CAR T-cell therapy for DLBCL, 37 patients underwent bridging RT or received salvage RT. RTs (median 36 gray) were well tolerated. Therapy response and disease control of CAR T-cell therapy were comparable after bridging RT or bridging systemic therapy. High-grade neurotoxicity tended to occur less frequently after bridging RT.After further disease progression, patients with localized relapses showed better outcomes, compared to those in advanced stage. In the subgroup with localized relapse, patients receiving salvage RT had an increased OS, vs. those without salvage RT (1-year OS rate 89% vs. 38%, p = 0.03). ConclusionOur analysis demonstrated that RT in combination with CAR T-cells led neither to high-grade toxicities, nor to a decreased response rate. We observed better outcomes of salvage therapies in patients with localized relapses vs. those with advanced stage relapses. Especially the patients who received salvage RTs for localized relapses seem to benefit more. Further analyses are necessary to clarify whether specific synergistic effects exist, such as an enhanced anti-tumor effect of CAR T-cells from RT sensitizing.

Surgical Management of Brain Tumors in Infants Under One Year of Age.

To comprehensively analyze clinical presentation, diagnosis, and management approaches of brain tumors in infants under one year of age. We conducted a retrospective analysis of clinical data retrieved from medical records of infants who underwent surgical treatment for intracranial mass lesions at our institution from January 2006 to December 2016. The data encompassed parameters such as age at diagnosis, symptoms, tumor location, histology, surgical procedures, adjuvant treatment, and survival outcomes. Cases involving dermoid, epidermoid cysts, and other skull-based lesions were excluded from the analysis. Our analysis identified twenty-three cases of brain tumors diagnosed within the first year of life, comprising 14 boys and 9 girls. The median age at diagnosis was 8.2 months, and the most common presenting symptoms were nausea and vomiting, as well as head circumference abnormalities. Successful gross total resection was achieved in 75.8% of patients, with choroid plexus papilloma being the most frequently encountered histopathological diagnosis. Eight patients received adjuvant chemotherapy, while one patient underwent salvage radiotherapy. The treatment of brain tumors in infants during their first year of life presents significant challenges. The affected patients exhibit diverse tumor pathologies occurring at various locations within the brain. Further research is warranted to establish optimal treatment options for this specific population.

The Utility of 68Ga-PSMA PET/CT in Decisions Regarding Administering Salvage Radiotherapy to Men with Prostate Cancer

Numerous papers have described 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)'s sensitivity in identifying prostate cancer (PCa) recurrence. This study aimed to characterize the role of 68Ga-PSMA PET/CT in deciding to re-irradiate pelvic structures. 68Ga-PSMA PET/CT scans performed at Sheba Medical Center over seven years in 113 men were reviewed. All had undergone radiation to the prostate (70, 61.9%) or post-radical prostatectomy radiation to the prostate fossa (PF) (43, 48.1%), and had local or oligometastatic PCa recurrence and received salvage radiotherapy (SRT) based on PET/CT findings. Mean age was 70.7 years. The mean grade group was 2.9; the mean prostate-specific antigen was 9.0. The 68Ga-PSMA PET/CT positive findings included: 37 (32.7%) in the prostate, 23 (20.4%) in seminal vesicles, 7 (6.2%) in the PF, and 3 (2.7%) in the seminal vesicle fossa. The mean standardized uptake value was 10.6 ± 10.2 (range: 1.4-61.6); the mean lesion size was 1.8 ± 3.5 mm (range: 0.5-5.1). SRT was directed toward the prostate and seminal vesicles in 48 (42.5%), PF in 18 (15.9%), and intrapelvic lymph node and bone in 47 (41.6%). Toxicities were mostly mild to moderate. 68Ga-PSMA PET/CT-identified relapse with targeted SRT was well-tolerated and may result in less onerous treatments.

Don't Put the CART Before the Horse: The Role of Radiation Therapy in Peri-CAR T-cell Therapy for Aggressive B-cell Non-Hodgkin Lymphoma

The optimal approach to incorporate radiation therapy (RT) in conjunction with chimeric antigen receptor (CAR) T-cell therapy (CART) for relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (bNHL) remains unclear. This study documented the RT local control rate among patients who received bridging radiation therapy (BRT) before CART and compares it with those who received salvage radiation therapy (SRT) after CART. This article further reports on a promising way to use SRT for post-CART disease and identifies predictors for RT in-field recurrence. We retrospectively reviewed 83 patients with r/r bNHL who received CART and RT, either as BRT pre-CART infusion (n=35) or as SRT post-CART infusion (n=48), between 2018 and 2021. RT was defined as comprehensive (compRT; ie, treated all sites of active disease) or focal (focRT). Limited disease was defined as disease amenable to compRT, involving <5 active disease sites. At time of RT, patients who received BRT before CART had bulkier disease sites (median diameter, 8.7 vs 5.5 cm; P=.01) and were treated to significantly lower doses (median equivalent 2-Gy dose, 23.3 vs 34.5 Gy; P=.002), compared with SRT post-CART. Among 124 total irradiated sites identified, 8 of 59 (13%) bridged sites and 21 of 65 (32%) salvaged sites experienced in-field recurrence, translating to 1-year local control rates (LC) of 84% and 62%, respectively (P=.009). Patients with limited post-CART disease (n=37) who received compSRT (n=26) had better overall survival (51% vs 12%; P=.028), freedom from subsequent progression (31% vs 0%; P < .001), and freedom from subsequent event (19% vs 0%; P=.011) compared with patients with limited disease who received focSRT (n=11). BRT followed by CART appears to be associated with improved LC compared with SRT in r/r bNHL. Nonetheless, SRT offers a promising salvage intervention for limited (<5 sites) relapsed post-CART disease if given comprehensively.

RBIO-06. CLINICAL AND MOLECULAR PREDICTORS OF RADIATION RESPONSIVENESS IN MENINGIOMAS: A MULTICENTER RETROSPECTIVE COHORT STUDY

Abstract BACKGROUND Aside from surgery, radiotherapy (RT) remains the only standard of care treatment for meningiomas. However, few studies have identified clinical/molecular biomarkers associated with responsiveness to RT and the optimal timing of RT after surgery remains controversial. We aimed to assess outcomes in a large multi-institutional cohort of RT-treated meningiomas to identify clinical factors and DNA methylation and RNA expression markers associated with progression-free survival (PFS) post-RT. METHODS Patients with intracranial meningiomas who underwent treatment with fractionated RT between 1997-2018 were included. DNA-methylation using the Illumina 850K EPICArray and RNA-sequencing were performed on tumours with sufficient tissue. Primary endpoints were radiographic recurrence of progression and time to progression from the time of RT completion. RESULTS 404 meningiomas were included for analysis. Of these, 167 (41.3%) recurred post-RT, usually within 5-years of RT. Previous RT to the meningioma, having a WHO grade 3 meningioma, and older age at diagnosis were independently associated with poorer PFS post-RT. Following propensity score matching, patients that received adjuvant RT had significantly better PFS post-RT compared to those that received salvage RT after recurrence (p=0.04). DNA methylation on 220 of these meningiomas segregated tumours into two distinct methylation groups (RT-resistant and RT-sensitive) based on unsupervised consensus clustering. DNA methylation were able to independently predict PFS post-RT better than all clinical factors. Differential RNA-expression analysis of these groups showed up-regulation of pathways involved in chromosome segregation and mitotic cell cycle and down-regulation of fatty acid metabolism pathways in RT-resistant meningiomas. CONCLUSION While there are a paucity of clinical factors that can reliably predict a meningioma’s response to RT, DNA methylation and RNA expression biomarkers may aid in differentiating RT-resistant meningiomas from RT-sensitive tumours. Patients that receive adjuvant RT may have prolonged PFS post-RT compared to those that receive salvage RT only after recurrence has already occurred.

Prognostic Utility of (18)F-Fluciclovine Positron Emission Tomography (FACBC) in Biochemically Recurrent (BCR) Prostate Cancer (PCa) Treated with Salvage Radiotherapy

<h3>Purpose/Objective(s)</h3> Patients with a biochemical recurrence after definitive radiotherapy or prostatectomy often undergo imaging to localize recurrent disease prior to salvage treatment. FACBC is a commonly utilized scan for this, but little is known about the prognostic utility of imaging metrics derived from FACBC scans in this setting. <h3>Materials/Methods</h3> This single-center retrospective study included 167 patients (pts) who had FACBC for BCR between 10/2017-10/2019. Clinical, pathological, imaging, and treatment data were collected by chart review. Pts who received salvage radiotherapy (SRT) were then identified and classified by whether their scan was positive or negative. Imaging metrics derived from positive scans included maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion metabolism (TLM). Freedom from biochemical progression (FFBP) and overall survival (OS) were compared between pts with positive and negative scans according to the Kaplan-Meier method, and for the above imaging metrics dividing each metric by its median value. Cox regression analysis for the following covariates was also performed: number of recurrence sites, SUVmax, MTV, and TLM. <h3>Results</h3> 71 pts received SRT; 34 had positive scans. The median FFBP for all patients who received SRT was 130 weeks (range 58.4-244.9). There was a statistical difference in FFBP between patients with negative and positive scans (median 130 vs. 128 weeks, p=0.039), but no difference in OS (median 130 vs. 146 weeks, p = 0.140). Among pts with positive scans, there was no difference in FFBP when considering high vs. low SUVmax, MTV, or TLF. There was also no difference when these factors were analyzed via cox regression. <h3>Conclusion</h3> In this retrospective cohort of 71 pts with FACBC PET scans treated with SRT, pts with a negative FACBC had a longer time to biochemical progression, but this did not affect overall survival. Although SUVmax, MTV, and TLM have been shown to be prognostic in other cancers with other PET tracers, none were prognostic in this cohort.