Local Progression-free Survival Research Articles

Comparison of En Bloc Resection and Intralesional Excision for Re-resection of Giant Cell Tumors of the Spine.

Re-resection of spinal giant cell tumors is an exceedingly difficult procedure. Moreover, the prognosis of patients with en bloc resection or intralesional excision for re-resection has rarely been reported. This study aimed to compare the prognostic value of en bloc resection with that of intralesional excision in patients undergoing re-resection for giant cell tumors of the spine. This retrospective analysis evaluated patients who underwent revision surgeries for relapse of giant cell tumors of the spine at our center between January 2005 and January 2021. Local progression-free survival represents the duration between en bloc resection or intralesional excision and tumor recurrence. Neurological recovery, survival rates, local control, and complications were evaluated. The Kaplan-Meier estimator was used for survival analysis. A total of 22 patients (nine men and 13 women) with a mean age of 34.1 (range 19-63) years were included. Significant statistical differences were found in the local tumor recurrence rate between patients treated with en bloc resection and those treated with intralesional excision (p < 0.05). The 5- and 10-year local progression-free survival rates were both 90% in the en bloc resection group, while in the intralesional excision group, the 5-year local progression-free survival rate was 80% with a 10-year rate of 45.7%. The en bloc resection group had a lower local tumor recurrence rate than that of the intralesional excision group (p < 0.05), but the former had a higher rate of complications (p = 0.015). This study revealed a low local recurrence rate in patients who underwent en bloc resection for giant cell tumors, while the perioperative complication rate was high.

Patterns of failure after radiosurgery for WHO grade 1 or imaging defined meningiomas: Long-term outcomes and implications for management

BackgroundWe analyzed long-term control and patterns of failure in patients with World Health Organization Grade 1 meningiomas treated with definitive or postoperative stereotactic radiosurgery at the authors’ affiliated institution. Methods96 patients were treated between 2004 and 2019 with definitive (n = 57) or postoperative (n = 39) stereotactic radiosurgery. Of the postoperative patients, 17 were treated adjuvantly following subtotal resection and 22 were treated as salvage at time of progression. Patients were treated to the gross tumor alone without margin or coverage of the dural tail to a median dose of 15 Gy. Median follow up was 7.4 years (inter-quartile range 4.8–11.3). Local control, marginal control, regional control, and progression-free survival were analyzed. ResultsLocal control at 5 and 10 years was 97 % and 95 %. PFS at 5 and 10 years was 94 % and 90 % with no failures reported after 6 years. Definitive and postoperative local control were similar at 5 (95 % [82–99 %] vs. 100 %) and 10 years (92 % [82–99 %] vs. 100 %). Patients treated with postoperative SRS did not have an increased marginal failure rate (p = 0.83) and only 2/39 (5 %) experienced recurrence elsewhere in the cavity. ConclusionsStereotactic radiosurgery targeting the gross tumor alone provides excellent local control and progression free survival in patients treated definitively and postoperatively. As in the definitive setting, patients treated postoperatively can be treated to gross tumor alone without need for additional margin or dural tail coverage.

Promising outcome of patients with recurrent glioblastoma after Gamma Knife-based hypofractionated radiotherapy

BackgroundThe role of Gamma Knife radiosurgery (GKRS) in recurrent glioblastoma remains unclear. The purpose of this study is to evaluate the effects of GKRS in a group of patients with recurrent glioblastoma, focusing on survival and safety. MethodsPatients undergoing GKRS for recurrent glioblastoma between September 2014 and April 2019 were included in this study. Relevant clinical and radiosurgical data, including GKRS-related complications, were recorded and analyzed. Overall survival (OS), local progression free survival (LPFS) and prognostic factors for outcome were thoroughly evaluated. ResultsFifty-three patients were analyzed (24 female, 29 male). The median age was 50 years (range, 19–78 years). The median GKRS treatment volume was 35.01 cm3 (range, 2.38-115.57 cm3). Twenty patients (38%) were treated with single fraction GKRS, while 33 (62%) were treated with GKRS-based hypofractionated stereotactic radiotherapy (HSRT). The median prescription dose for single fraction GKRS, 3-fractions HSRT and 5-fractions HSRT were 16 Gy (range, 10−20 Gy), 27 Gy (range, 18−33 Gy) and 25 Gy (range, 25−30 Gy), respectively. The median LPFS and OS times were 8.1 months and 11.4 months after GKRS, respectively. HSRT and Bevacizumab were associated with improved LPFS, while HSRT alone was associated with longer OS. ConclusionOur findings suggested that HRST would likely improve LPFS and OS in definite settings; the addition of Bevacizumab to GKRS was associated with increased rates of local control. No major complications were reported. Further prospective studies are warranted to confirm our findings.

Efficacy and safety analysis of stereotactic body radiotherapy for brain multi-metastases in non-small cell lung cancer patients.

Lung cancer is prone to metastasize to the brain, which is difficult for surgery and leads to poor prognosis due to poor chemotherapy efficacy. Our aim is to evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for brain multi-metastases. In the retrospective study, a total of 51 non-small cell lung cancer (NSCLC) patients with brain multi-metastases (3-5 metastases) receiving SBRT in the local hospital between 2016 and 2019 were enrolled for analyzing the efficacy and safety of SBRT. The primary endpoints included 1-year local control rate, radiotherapy toxicity, overall survival and progression-free survival. The median follow-up for the enrolled patients was 21 months, and the 1-year and 2-year OS rates were 82.4% and 45.1%, respectively. Demographic analysis showed no significant differences between SBRT alone and combination with whole brain radiotherapy in clinical characteristics including age, gender and Eastern Cooperative Oncology Group performance status. The 1-year local control rate was 77.3% (17/22) for SBRT alone, which was comparable to 79.3% (23/29) of combined radiotherapy. Cox proportional hazard regression demonstrated that the prognostic benefit of combining WBRT was not significantly superior to SBRT alone (HR = 0.851, P= 0.263). Their radiotherapy toxicity rate was lower in SBRT alone group (13.6%, vs. 44.8% for combination; P= 0.017). The current research suggested that SBRT alone could effectively relieve tumor burden and improve the prognosis and quality of life for NSCLC patients with brain multi-metastases, which should be validated in further prospective clinical trials.

Craniospinal irradiation for CNS leukemia: rates of response and durability of CNS control.

Management of CNS involvement in leukemia may include craniospinal irradiation (CSI), though data on CSI efficacy are limited. We retrospectively reviewed leukemia patients who underwent CSI at our institution between 2009 and 2021 for CNS involvement. CNS local recurrence (CNS-LR), any recurrence, progression-free survival (PFS), CNS PFS, and overall survival (OS) were estimated. Of thirty-nine eligible patients treated with CSI, most were male (59%) and treated as young adults (median 31 years). The median dose was 18Gy to the brain and 12Gy to the spine. Twenty-five (64%) patients received CSI immediately prior to allogeneic hematopoietic cell transplant, of which 21 (84%) underwent total body irradiation conditioning (median 12Gy). Among 15 patients with CSF-positive disease immediately prior to CSI, all 14 assessed patients had pathologic clearance of blasts (CNS-response rate 100%) at a median of 23 days from CSI start. With a median follow-up of 48 months among survivors, 2-year PFS and OS were 32% (95% CI 18-48%) and 43% (95% CI 27-58%), respectively. Only 5 CNS relapses were noted (2-year CNS-LR 14% (95% CI 5-28%)), which occurred either concurrently or after a systemic relapse. Only systemic relapse after CSI was associated with higher risk of CNS-LR on univariate analysis. No grade 3 or higher acute toxicity was seen during CSI. CSI is a well-tolerated and effective treatment option for patients with CNS leukemia. Control of systemic disease after CSI may be important for CNS local control. CNS recurrence may reflect reseeding from the systemic space.

Long-term outcomes of metastasis-directed stereotactic body radiation therapy in metastatic nasopharyngeal carcinoma.

The study aims to evaluate the outcomes of metastasis-directed stereotactic body radiation therapy (SBRT) in metastatic nasopharyngeal carcinoma (mNPC). We reviewed all SBRT conducted in patients with mNPC in our institution between 2013 and 2022. Systemic therapy was performed with chemotherapy with or without anti-programmed death-1 (PD-1) therapy. Local treatment delivered with ablative purpose in stereotactic setting with dose/fraction ≥5 Gy was evaluated. Kaplan-Meier analyses were used to determine the rates of local control (LC), progression-free survival (PFS), and overall survival (OS). Univariate and multivariate analyses were performed by Cox regression. A total of 54 patients with 76 metastatic sites receiving SBRT were analyzed. Median follow-up was 49 months. The 3-year LC, PFS, and OS rates were 89.1%, 29.4%, and 57.9%, respectively. Adding a PD-1 inhibitor to SBRT tended to prolong median OS (50.1 vs. 32.2 months, p = 0.068). Patients receiving a biologicaleffective dose (BED, α/β = 10) ≥ 80 Gy had a significantly longer median OS compared to those who received a lower dose (not reached vs. 29.5 months, p = 0.004). Patients with oligometastases (1-5 metastases) had a better median OS (not reached vs. 29.5 months, p < 0.001) and PFS (34.3 vs. 4.6 months, p < 0.001). Pretreatment EBV-DNA and maintenance therapy were also significant predictors for OS. Metastatic NPC patients could benefit from metastases-directed SBRT in combination with systemic therapy.

Efficacy of Yttrium-90 Transarterial Radioembolisation in Advanced Hepatocellular Carcinoma: An Experience With Hybrid Angio-Computed Tomography and Glass Microspheres

BackgroundHepatocellular carcinoma is one of the most common malignancies worldwide. Transarterial radioembolization (TARE) involves selective intra-arterial administration of microspheres loaded with a radioactive compound like Yttrium90. Conventionally, C-arm based cone-beam computed tomography has been used extensively during TARE. However, Angio-CT is a relatively new modality which combines the advantages of both fluoroscopy and Computed Tomography (CT). There is scarce literature detailing the use of Angio-CT in Y90 TARE. MethodsThis was a retrospective study of primary liver cancer cases in which TARE procedure was done from November 2017 to December 2021. Glass-based Y-90 microspheres were used in all these cases. All the cases were performed in the hybrid Angio-CT suite. A Single Photon Emission Computed Tomography – Computed Tomography (SPECT-CT) done post planning session determined the lung shunt fraction and confirmed the accurate targeting of the lesion. Post drug delivery, PET-CT was obtained to confirm the distribution of the Y-90 particles. The technical success, median follow-up, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were recorded. ResultsA total of 56 hepatocellular carcinoma patients underwent TARE during this period out of which 36 patients (30 males and 6 females) underwent Y90 TARE. The etiology of cirrhosis included non-alcoholic steatohepatitis (NASH) (11), hepatitis C (HCV) (11), hepatitis B (HBV) (9), metabolic dysfunction and alcohol associated liver disease (MetALD) (2), alcoholic liver disease (ALD) (1), cryptogenic (1) and autoimmune hepatitis (AIH) (1). The technical success was 100% and median follow-up was 7 months (range: 1 - 32 months). The median OS was 15 months (range 10.73 – 19.27 months; 95% CI) and the median local PFS was 4 months (range 3.03 – 4.97 months; 95% CI). The ORR (best response, CR + PR) was 58%. No major complications were seen in this study. ConclusionTARE is a viable option for liver cancers in all stages but more so in the advanced stages. The use of Angio-CT in TARE aids in the precise delivery of the particles to the tumour and avoids non-target embolization.

Stereotactic radiosurgery of brain metastases: a retrospective study

BackgroundSingle-fraction stereotactic radiosurgery (SRS) is an established standard for radiation therapy of brain metastases although recent developments indicate that multi-fractionated stereotactic radiotherapy (FSRT) results in lower radiation necrosis especially for larger metastases, and the same or even better local control in comparison to SRS.MethodsSeventy-two patients with 111 brain metastases received SRS with a single dose of 18 Gy between September 2014 and December 2021. The dose prescription was either 18 Gy given to the enclosing 80% isodose with a normalization to Dmax = 100% of 22.5 Gy (part I) or 18 Gy = D98, while D0.03 cc of 21.6–22.5 Gy was accepted (part II). The study retrospectively evaluated local progression-free survival (LPFS), response on the first follow-up magnetic resonance imaging (MRI), and radiation necrosis.ResultsMelanoma brain metastases (n = 44) were the most frequent metastases. The median gross tumor volume (GTV) was 0.30 cm³ (IQR, 0.17–0.61). The median follow-up time of all patients was 50.8 months (IQR, 30.4–64.6). Median LPFS was 23.5 months (95%CI 17.2, 29.8). The overall LPFS rates at 12-, 18-, 24- and 30 months were 65.3%, 56.3%, 46.5%, and 38.8%. Brain metastases with radioresistant histology (melanoma, renal cell cancer, and sarcoma) showed a 12-month LPFS of 60.2%, whereas brain metastases with other histology had a 12-month LPFS of 70.1%. The response of brain metastases on first follow-up MRIs performed after a median time of 47 days (IQR, 40–63) was crucial for long-term local control and survival. Eight brain metastases (7.2%) developed radiation necrosis after a median time of 18.4 months (IQR, 9.4–26.5). In multivariate analyses, a GTV > 0.3 cm³ negatively affected LPFS (HR 2.229, 95%CI 1.172, 4.239). Melanoma, renal cell cancers, and sarcoma had a lower chance of LPFS in comparison to other cancer types (HR 2.330, 95%CI 1.155, 4.699).ConclusionsOur results indicate a reasonable 1-year local control of brain metastases with radiosensitive histology. Radioresistant metastases show a comparatively poor local control. Treatment refinements merit exploration to improve local control of brain metastases.Trial registrationThis study is retrospectively registered (ethics approval number 23-3451-104).

The Clinical Efficacy of Colorectal Cancer Patients with Pulmonary Oligometastases by Sterotactic Body Ablative Radiotherapy: A Meta-Analysis.

There is increasing interest in the efficacy of stereotactic ablative radiotherapy (SABR) for treating colorectal cancer (CRC) patients with oligometastases (OM), recently. The purpose of this meta-analysis was to evaluate local control (LC), progression-free survival (PFS), and overall survival (OS) of CRC patients with pulmonary OM treated with SABR and toxicities. Studies that reported SABR for CRC patients with pulmonary OM were searched from MEDLINE and Embase. Treatment outcomes including LC, PFS, OS, and toxicities of grade 3 or higher were assessed. A total of 19 studies with 1,668 patients were chosen for this meta-analysis. Pooled 1-, 2-, and 3-year LC rates were 83.1%, 69.3%, and 63.9%, respectively. PFS rates were 44.8%, 26.5%, and 21.5% at 1, 2, and 3 years, respectively. OS rates at 1-, 2-, and 3-year were 87.5%, 69.9%, and 60.5%, respectively. The toxicity rate of grade 3 or higher was 3.6%. The effect of dose escalation was meta-analyzed using available studies. Application of SABR to CRC patients with pulmonary OM achieved modest local control with acceptable toxicity according to the present meta-analysis. Further studies establishing the clinical efficacy of SABR are guaranteed.

SBRT of Spinal Metastases Using a Simultaneous Integrated Boost Concept in Oligometastatic Cancer Patients Is Safe and Effective.

(1) Purpose: To assess the safety and effectivity of stereotactic body radiotherapy (SBRT) on spinal metastases utilizing a simultaneous integrated boost (SIB) concept in oligometastatic cancer patients. (2) Methods: 62 consecutive patients with 71 spinal metastases received SIB-SBRT between 01/2013 and 09/2022 at our institution. We retrospectively analyzed toxicity, local tumor control (LC), and progression-free (PFS) and overall survival (OS) following SIB-SBRT and assessed possible influencing factors (Kaplan-Meier estimator, log-rank test and Cox proportional-hazards model). (3) Results: SIB-SBRT was delivered in five fractions, mostly with 25/40 Gy (n = 43; 60.56%) and 25/35 Gy (n = 19, 26.76%). Estimated rates of freedom from VCF were 96.1/90.4% at one/two years. VCF development was significantly associated with osteoporosis (p < 0.001). No ≥ grade III acute and one grade III late toxicity (VCF) were observed. Estimated LC rates at one/two years were 98.6/96.4%, and histology was significantly associated with local treatment failure (p = 0.039). Median PFS/OS was 10 months (95% CI 6.01-13.99)/not reached. Development of metastases ≥ one year after initial diagnosis and Karnofsky Performance Score ≥ 90% were predictors for superior PFS (p = 0.038) and OS (p = 0.012), respectively. (4) Conclusion: Spinal SIB-SBRT yields low toxicity and excellent LC. It may be utilized in selected oligometastatic patients to improve prognosis. To the best of our knowledge, we provide the first clinical data on the toxicity and effectivity of SIB-SBRT in spinal metastases in a larger patient cohort.

Progression-free survival assessment by local investigators versus blinded independent central review in randomized clinical trials in metastatic breast cancer: A systematic review and meta-analysis

IntroductionIn randomized clinical trials (RCTs), blinded independent central review (BICR) is used to minimize heterogeneity and bias associated with radiological response evaluation by local investigators. However, BICR adds costs and complexity to the trial management. We assessed the discrepancy index between progression-free survival (PFS) assessment by local investigators and by BICR in RCTs conducted in patients with metastatic breast cancer (MBC). MethodsA systematic search of PubMed, Embase, Cochrane databases and conference proceedings (ASCO, SABCS, ESMO) was performed up to January 4, 2023 (PROSPERO: CRD42021229865). All RCTs published from 2000 to 2022, including MBC patients treated in first- or second-line, and reporting PFS assessed by local investigators and BICR were included. A discrepancy index between BICR-assessed and investigator-assessed HR was calculated for each trial and an overall combined DI was obtained using a fixed-effects model. The agreement between hazard ratios (HR) of PFS assessed by local investigators and BICR was measured using intraclass correlation coefficient (ICC). ResultsWe analyzed 24 studies including 13,168 patients. Among them, 19 (79%) were in first-line, 18 (75%) were phase III trials and 23 (96%) had PFS as primary endpoint. The overall combined discrepancy index was 0.97 (95%CI 0.85–1.10; ICC 0.831, p < 0.001) suggesting no statistically significant difference in PFS assessment between local investigators and BICR. This result was consistent across all analyzed subgroups. ConclusionsThe good concordance between local investigator and BICR assessments supports the reliability of local investigator-assessed PFS as primary endpoint for RCTs in MBC and questions the practical utility of implementing BICR in all RCTs.

Prognostic Outcomes of Cutaneous Squamous Cell Carcinoma in Solid Organ Transplant Recipients: A Retrospective Comparative Cohort Study.

Cutaneous squamous cell carcinoma (cSCC) is the second most common cutaneous neoplasm, and its incidence is on the rise. While most cSCCs have an excellent prognosis, certain risk factors, especially immunosuppression, have been associated with higher rates of local recurrence (LR), metastasis, and poor prognosis. This study aims to assess the risk factors for LR and metastasis development in cSCC among solid organ transplant recipients (SOTRs) and compare these rates with those in immunocompetent patients. A retrospective observational study included cSCC cases from the University Hospital Reina Sofía in Córdoba, Spain, between 2002 and 2019. Demographic, clinical, and histopathological data were collected. Local recurrence and metastasis rates were analyzed, along with progression-free survival. Univariate analyses were performed to identify prognostic factors in SOTRs. Among 849 cSCC cases, we found higher rates of local recurrence and metastasis in tumors developed by SOTRs compared to those in immunocompetent individuals. However, no significant differences in local recurrence, metastasis, or progression-free survival were observed between the two groups. Risk factors for adverse outcomes in SOTRs included tumor size > 2 cm, depth > 4 mm, and a higher Clark level. A total of 34.4% of SOTRs developed a second primary cSCC during the follow-up. In our study, cSCCs in SOTRs did not exhibit statistically significant differences in the rates of adverse outcomes compared to immunocompetent patients. The prognosis of cSCCs in SOTRs may be more related to other tumor-dependent risk factors than to the immunosuppression status itself. Future studies are needed to refine risk stratification and follow-up protocols to ensure the optimal management of high-risk cSCC cases, particularly among immunosuppressed patients.

Stereotactic body radiation therapy for adrenal gland metastases: A multi-institutional outcome analysis

AimThe adrenal gland is a common site of metastasis with a rate of up to 27% in autopsy series. The incidence of these metastases is increasing due to greater use of Positron Emission Tomography scans and improved overall survival of patients with metastatic cancers. Stereotactic body radiation therapy (SBRT) is a non-invasive treatment option for metastasis. The aim of this study is to assess prognostic factors influencing local control, progression-free and overall survival in oligometastatic patients treated with SBRT for an adrenal metastasis. MethodsIn this multicentric retrospective study, we included patients with adrenal metastases treated with SBRT between 2010 and 2021 in eleven french centers. All primary tumors were included. ResultsA total of 110 patients treated for 121 adrenal lesions were included. Non-small-cell lung cancer was the predominant histologic type (55.4 %). Eighty-two percent of patients had at least 2 metastatic sites. The median Planning Target Volume was 70 cm3 with a median prescription dose of 40 Gray (Gy). The mean Biologically Effective Dose (BED) 10 dose was 74.2 Gy. Local control at 1 and 2 years was 85.9 % and 72.5 % respectively. The median overall survival and progression-free survival were 31.6 and 8.5 months respectively. Local control was significantly improved by systemic treatment one month before or after SBRT (p = 0.009) and by a BED10 greater than or equal to 50 Gy (p = 0.003).In multivariate analysis, oligometastatic presentation (p = 0.009) and a metachronous metastatic presentation (p = 0.008) were independent factors for progression-free survival.Tolerance was excellent, no grade 3 and 4 toxicities were described due to SBRT. ConclusionStereotactic radiotherapy of adrenal metastases makes possible a local control of more than 85% at one year and was well tolerated. The factors influencing survival in oligometastatic patients still need to be found in order to better select those who benefit the most from this type of treatment.

A Prospective Study Assessing the Efficacy and Toxicity of Stereotactic Body Radiation Therapy for Oligometastatic Bone Metastases

PurposeStereotactic body radiation therapy (SBRT) is a promising treatment for oligometastatic disease in bone due to its delivery of high dose to target tissue and minimal dose to surrounding tissue. The purpose of this study is to assess the efficacy and toxicity of this treatment in patients with previously unirradiated oligometastatic bony disease. Materials and MethodsIn this prospective phase II trial, patients with oligometastatic bone disease, defined as ≤3 active sites of disease, were treated with SBRT at XXXX between December 2016 and May 2019. SBRT dose and fractionation regimen were not protocol-mandated. Local progression-free survival (LPFS), progression-free survival (PFS), prostatic specific antigen (PSA) progression, and overall survival (OS) were reported. Treatment-related toxicity was also reported. ResultsA total of 98 patients and 126 lesions arising from various tumor histologies were included in this study. The median age of patients enrolled was 72.8 years (80.6% male, 19.4% female). Median follow-up was 26.7 months. The most common histology was prostate cancer (68.4%, 67/98). The most common dose prescriptions were 27/30 Gy in 3 fractions (27.0%, 34/126), 30 Gy in 5 fractions (16.7%, 21/126), or 30/35 Gy in 5 fractions (16.7%, 21/126). Multiple doses per treatment regimen reflect dose painting employing the lower dose to the clinical target volume (CTV) and higher dose to the gross tumor volume (GTV). Four patients (4.1%, 4/98) experienced local progression at one site for each patient (3.2%, 4/126). Among the entire cohort, 2-year LPFS (including death without local progression) was 84.8%, 2-year PFS (including deaths as well as local, distant, and PSA progression) was 47.5%, and 2-year OS was 87.3%. Twenty-six patients (26.5%, 26/98) developed treatment-related toxicities. ConclusionsOur study supports existing literature in showing that SBRT is effective and tolerable in patients with oligometastatic bone disease. Larger phase III trials are necessary and reasonable to determine long-term efficacy and toxicities.

Preoperative Intensified Chemoradiation with Intensity-Modulated Radiotherapy and Simultaneous Integrated Boost Combined with Capecitabine in Locally Advanced Rectal Cancer: Long-Term Outcomes of a Real-Life Multicenter Study

Background: Despite the feasibility and promising activity data on intensity-modulated RT and simultaneous integrated boost (IMRT-SIB) dose escalation in preoperative chemoradiation (CRT) for locally advanced rectal cancer (LARC), few data are currently available on long-term outcomes. Patients and Methods: A cohort of 288 LARC patients with cT3-T4, cN0-2, cM0 treated with IMRT-SIB and capecitabine from March 2013 to December 2019, followed by a total mesorectal excision (TME) or an organ-preserving strategy, was collected from a prospective database of 10 Italian institutions. A dose of 45 Gy in 25 fractions was prescribed to the tumor and elective nodes, while the SIB dose was prescribed according to the clinical practice of each institution on the gross tumor volume (GTV). Concurrent capecitabine was administered at a dose of 825 mg/m2 twice daily, 7 days a week. The primary objective of the study was to evaluate long-term outcomes in terms of local control (LC), progression-free survival (PFS) and overall survival (OS). The secondary objective was to confirm the previously reported feasibility, safety and efficacy (pCR, TRG1-2 and downstaging rates) of the treatment in a larger patient population. Results: All patients received a dose of 45 Gy to the tumor and elective nodes, while the SIB dose ranged from 52.5 Gy to 57.5 Gy (median 55 Gy). Acute gastrointestinal and hematologic toxicity rates of grade 3–4 were 5.7% and 1.8%, respectively. At preoperative restaging, 36 patients (12.5%) with complete or major clinical responses (cCR or mCR) were offered an organ-preserving approach with local excision (29 patients) or a watch and wait strategy (7 patients). The complete pathologic response rate (pCR) in radically operated patients was 25.8%. In addition, 4 TME patients had pT0N1 and 19 LE patients had pT0Nx, corresponding to an overall pT0 rate of 31.3%. Of the 36 patients selected for organ preservation, 7 (19.5%) required the completion of TME due to unfavorable pathologic features after LE or tumor regrowth during W-W resulting in long-term rectal preservation in 29 of 288 (10.1%) of the total patient population. Major postoperative complications occurred in 14.2% of all operated patients. At a median follow-up of 50 months, the 5-year PFS and OS rates were 72.3% (95% CI: 66.3–77.4) and 85.9% (95% CI: 80.2–90.1), respectively. The 5-year local recurrence (LR) rate was 9.2% (95% CI: 6.0–13.2), while the distant metastasis (DM) rate was 21.3% (95% CI: 16.5–26.5). The DM rate was 24.5% in the high-risk subset compared to 16.2% in the low-intermediate risk group (p = 0.062) with similar LR rates (10% and 8%, respectively). On multivariable analysis, cT4 and TRG3–5 were significantly associated with worse PFS, OS and metastasis-free survival. Conclusions: Preoperative IMRT-SIB with the moderate dose intensification of 52.5–57.5 Gy (median 55 Gy) and the full dose of concurrent capecitabine confirmed to be feasible and effective in our real-life clinical practice. Organ preservation was shown to be feasible in carefully selected, responsive patients. The favorable long-term survival rates highlight the efficacy of this intensified treatment program. The incorporation of IMRT-SIB with a more effective systemic therapy component in high-risk patients could represent a new area of investigational interest.

Genetic Alterations of Follicular Lymphoma Can Predict Response to Very Low Dose Radiotherapy

Introduction Follicular lymphoma (FL) is typically indolent, but relapses and transformation to higher grade disease are common. FL is often radiosensitive and can show complete response (CR) even to very low dose radiotherapy (VLDRT, 4Gy). There are no known genetic markers of FL radiosensitivity. We sought to identify molecular signatures of FL radiosensitivity to aid in patient selection for VLDRT. Methods We analyzed our institutional database and identified 110 FL patients with 113 tumors treated with radiotherapy (RT) and preexisting MSK-IMPACT, a targeted exon sequencing panel. For each patient, we collected key clinicodemographic information including pre- and post-RT treatment history, prior large cell lymphoma, and Ann Arbor stage at RT. For treated tumors, we obtained tumor site, grade, diameter, maximum SUV, BCL2 translocation (trans) status through fluorescence in situ hybridization, RT dose and fractionation, and the treatment strategy ( i.e. treating all sites of disease vs a subsite of disease). Tumor site was dichotomized by pelvic tumors vs all others, as this was the most frequently altered site. The presence of mutant (mut) genes compared to wild type (WT) were associated with RT response, measured by PET scan within 6 months of RT, using logistic regression. Log-rank testing and Cox proportional hazards models were used to analyze local progression free survival (LPFS), censored at start of unplanned therapy, with 2-year (2y) survival reported. Multivariate modeling was used to adjust gene associations with outcomes, controlling for the clinicodemographic and tumor characteristics mentioned above. Results The patient and tumor characteristics are summarized in table 1. We found CREBBP to be the most frequently altered gene (66% of tumors). We identified 5 signatures of altered genes, most of which showed altered CREBBP and relatively long LPFS (e.g. one signature showed CREBBP mut, TNFRSF14 mut and IRF8/STAT6 mut with a 2y LPFS 78%); however, one signature with concurrent KMT2D mut and altered BCL2 including trans and mut had significantly shorter LPFS than all other signatures (2y LPFS 47%, p &amp;lt; 0.01) and lower odds of CR relative to the other signatures (p= 0.03). CREBBP mut was the only alteration associated with increased odds of CR (Odds ratio: 2.39 (95% CI: 1.06-5.37, p = 0.04), and this effect remained significant after adjusting for pelvic disease site (p=0.04). Mutations of BCL2, IRF8, and KMT2D were associated with LPFS using log-rank testing (p&amp;lt;0.01, p=0.02, and p=0.04, respectively). BCL2 mut or concurrent BCL2 mut and BCL2 trans (mut/trans) had shorter LPFS for the overall cohort (p&amp;lt;0.01 for both), while for VLDRT, only BCL2 mut/trans was associated with shorter LPFS (p=0.02). In the VLDRT cohort, we found that CREBBP histone acetyltransferase (HAT) mut was associated with improved LPFS compared to WT (n=39, 2y LPFS 74% vs 52%, HR:0.41 (95% CI: 0.18-0.93, p=0.03)), but this was not observed for tumors receiving &amp;gt;4Gy (n=44, HR: 1.27 (95% CI: 0.32-5.08), p=0.74)). We observed that either BCL2 mut, BCL2 trans, or BCL2 mut/trans and CREBBP HAT WT had a 2y LPFS of 13% whereas BCL2 mut, BCL2 trans or BCL2 mut/trans and CREBBP HAT mut had a 2y LPFS of 83% (p&amp;lt;0.01), and this relationship persisted on multivariate analysis (Figure 1). Conclusions Incorporating genetic signatures associated with radiosensitivity, and specifically alterations involving BCL2 and CREBBP, may independently improve patient selection for RT. CREBBP HAT domain mutations are potentially targetable and may have important implications for augmenting radiosensitivity to VLDRT.

Insights into Presentation and Outcomes of Localized Immunoglobulin Light Chain Amyloidosis: A 12-Year Experience of a Large Academic Center

Introduction : Localized immunoglobulin light chain amyloidosis (Loc-AL) is an ultra-rare disease caused by the local deposition of misfolded AL fibrils. To date, limited data exists on reporting patterns of disease presentation and long-term outcomes. The primary aim of this study is to describe our institution's experience of patients with Loc-AL, including disease presentation, management, and risk for local and systemic progression. Methods: We retrospectively analyzed medical records of 3108 patients with amyloidosis and selected 141 (5%) patients with biopsy proven Loc-AL treated at our institution between 1/1/2010 and 7/1/2023. Patients with evidence of systemic AL disease involving the bone marrow and/or major organs, such as heart, kidney, liver, and nervous system on initial assessment were excluded. AL amyloid typing was available in all cases; mass spectrometry was performed in 85 (60%) cases. Chi-squared test and Kaplan-Meier method were used for statistical analysis. Results: Of the 141 patients with Loc-AL included in this analysis, 79 (56%) were female and 117 (83%) were White. The median age at diagnosis was 67 (range 18-92) years. The sites of involvement included: 22% lower respiratory system (16% lung/pleura, 4% tracheobronchial system, 2% multi-site), 18% gastrointestinal system (8% upper GI [esophagus, stomach, duodenum] tract, 9% lower GI [colon, rectum] tract, and 1% other), 18% head &amp; neck (eye [conjunctiva, lacrimal sac], auditory canal, oral cavity, pharynx/oropharynx), 9% urothelial system (prostate, bladder, ureteral, urethra), 9% soft tissue, 7% skin, 7% breast, 4% upper respiratory system (vocal cords, larynx, subglottic area), and 6% others (including two cases of central nervous system involvement) (Figure 1). At presentation, 75 (53%) patients were symptomatic, whereas in the remaining 65 (47%) patients Loc-AL was an incidental finding. Bone marrow biopsy, fat pad biopsy and cardiac imaging (echocardiogram and/or cardiac MRI) were obtained in 67 (48%), 20 (14%) and 105 (74%) patients, respectively. All bone marrow and pad biopsies were negative for AL amyloid; in addition, no bone marrow biopsy revealed monoclonal plasma cells. A serum monoclonal protein (sMP) was detected in only 29 (20%) patients, 12 of whom had serum light chain different from the localized light chain type. Of the 29 patients with positive sMP, 20 had IgG isotype, 6 had IgM, 2 IgA and 1 had light chains only. Abnormal free light chain ratio was reported in 17 (12%) patients, 6 of whom had a positive sMP. Twenty-four (17%) patients had coexistent autoimmune disease and 13 (9%) co-existent malignancy that was not plasma cell related. First line management approaches included: observation with or without supportive care (57%), surgical resection (38%), radiotherapy (2%), systemic therapy (3.5% chemotherapy, 3.5% steroids) and topical therapy (3.5%). Of the 5 patients who received chemotherapy, 4 had plasma cell-directed therapy; of them, 3 maintained stable disease based on follow-up imaging and 1 had no response. The fifth patient received rituximab for their underlying MALT lymphoma. Seventeen patients (12%) required repeated interventions (median 1 [range 1-4]) for local disease progression. The most common sites requiring repeated interventions were: genitourinary system (29%), respiratory system (24%) and breast (18%). No patient progressed to systemic AL. There were no deaths attributed to Loc-AL. The median follow-up time was 46.7 months. The 2- and 5-year local progression free survival rates were 93%, and 78%, respectively, and there was no difference with regard to site of disease. The estimated median overall survival (OS) was not reached; the 2- and 5-year OS rates were 99% and 92%, respectively (Figure 2). Conclusion: The results of our study suggest thatLoc-AL has an excellent prognosis, and does not progress to systemic AL disease. A significant number of patients have no symptoms at diagnosis. Observation and/or surgical removal are usually adequate initial approaches to manage Loc-AL, however, a small percentage of patients can relapse locally requiring repeated interventions for symptom control. Consultation with a hematologist is important to rule out systemic disease.

A novel endoscopic nasopharyngectomy by low-temperature plasma radiofrequency ablation in localized recurrent nasopharyngeal carcinoma.

Endoscopic nasopharyngectomy (ENPG) with en bloc resection has been well accepted in resectable localized recurrent nasopharyngeal carcinoma (rNPC), but it is a difficult technique to master for most otorhinolaryngology head and neck surgeons. Ablation surgery is a new and simplified method to remove tumors. We designed a novel method using low-temperature plasma radiofrequency ablation (LPRA) and evaluated the survival benefit. A total of 56 localized rNPC patients were explained in detail and retrospectively analyzed. The surgery method was ablated from the resection margin to the center of the tumor. The postmetastatic overall survival (OS), local relapse-free survival (LRFS) rate, progression-free survival (PFS) and distant metastasis-free survival (DMFS) were analyzed using the Kaplan-Meier method and compared by the log-rank test. All surgeries were successfully performed without any severe postoperative complications or deaths. The median operation time of ablation and harvested NSFF respectively were 29 min (range, 15-100 min) and 101 min (range, 30-180 min). The average number of hospital days postoperation was 3 days (range, 2-5 days). All cases (100.0%) had radical ablation with negative resection margins. The nasopharyngeal defects were completely re-epithelialized in 54 (96.4%) patients. As of the data cutoff (September 3, 2023), the median follow-up time was 44.3 months (range, 17.1-52.7 months, 95% CI: 40.4-48.2). The 3-year OS, LRFS, PFS and DMFS of the entire cohort were 92.9% (95% CI: 0.862-0.996), 89.3% (95% CI: 0.813-0.973), 87.5% (95% CI: 0.789-0.961), and 92.9% (95% CI: 0.862-0.996), respectively. Cycles of radiotherapy were independent risk factors for OS (p = 0.003; HR, 32.041; 95% CI: 3.365-305.064), LRFS (p = 0.002; HR, 10.762; 95% CI: 2.440-47.459), PFS (p = 0.004; HR, 7.457; 95% CI: 1.925-28.877), and DMFS (p = 0.002; HR, 34.776; 95% CI: 3.806-317.799). Radical endoscopic nasopharyngectomy by using low-temperature plasma radiofrequency ablation is a novel, safe and simplified method to master and disseminate for treating resectable rNPC. However, further data and longer follow-up time are needed to prove its efficacy.

Incorporating radiation with anti-CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory non-Hodgkin lymphoma: A multicenter consensus approach.

Anti-CD19 chimeric antigen receptor T-cell therapy (CART) has revolutionized the outcomes of relapsed and/or refractory B-cell non-Hodgkin lymphoma. However, CART is still limited by its availability, toxicity, and response durability. Not all patients make it to the CART infusion phase due to disease progression. Among those who receive CART, a significant number of patients experience life-threatening cytokine release syndrome toxicity, and less than half maintain a durable response with the majority relapsing in pre-existing sites of disease present pre-CART. Radiation therapy stands as a promising peri-CART and salvage treatment that can improve the outcomes of these patients. Evidence suggests that bridging radiotherapy prior to CART controls the disease during the manufacturing period, augments response rates and local control, cytoreduces/debulks the disease and decreases the severity of cytokine release syndrome, and may prolong disease-free intervals and survival especially in patients with bulky disease. Consolidative radiotherapy for residual post-CART disease alters the pattern of relapse and improves local recurrence-free and progression-free survivals. Salvage radiotherapy for relapsed post-CART disease has favorable survival outcomes when delivered comprehensively for patients with limited relapsed disease and palliates symptoms for patients with diffuse relapsed disease. The biology of the disease during the peri-CART period is poorly understood, and further studies investigating the optimal timing and dosing of radiation therapy (RT) are needed. In this review, we tackle the most significant challenges of CART, review and propose how RT can help mitigate these challenges, and provide The Mayo Clinic experts' approach on incorporating RT with CART.

RADT-24. A PROSPECTIVE TRIAL EVALUATING THE EFFICACY OF REIRRADIATION TO BONY METASTASES WITH STEREOTACTIC BODY RADIATION THERAPY

Abstract INTRODUCTION Bone metastasis is common in advanced-stage cancer patients. While reirradiation of metastatic tumors offers significant symptom control, major limits exist on the possible dose delivered to previously irradiated disease sites. Stereotactic body radiation therapy (SBRT) offers the potential to avoid delivering toxic radiation doses to the spinal cord and other organs at risk by delivering large doses with steep dose gradients. METHODS We developed a prospective study including 44 patients with recurrent bone metastasis that were treated to assess the effectiveness of SBRT on local control at or before 6 months as a primary endpoint and local progression-free survival (LPFS), Progression-free survival (PFS), and overall survival (OS) as a secondary objective. RESULTS Patients median age was 62.5 years (22.7% female and 77.3% male). The majority of patients received reirradiation to a spinal lesion (29/44, 65.9%) of various primary disease sites predominantly prostate (13/44, 29.5%), lung (8/44, 18.2%), and renal cell (5/44, 11.4%). The most common dose prescriptions were 30 Gy in 5 fractions (24/44, 54.5%). Of the participants, 41 (93.2%) experienced local control at or before 6 months, with 3.6 median months to local progression for those who progressed. 48% and 36.5% of the cohort maintained LPFS at 2 years, and 3 years respectively with a local progression-free rate of 89.5% at 2 and 3 years. OS was maintained in 50.9% and 38.8% of patients at 2 years and 3 years respectively. CONCLUSION SBRT offers an effective and less toxic approach for the reirradiation of recurrent metastatic tumors as it can prevent associated toxicities to the surrounding normal tissues and maintain a local progression-free rate in a large percentage of patients. We believe that more clinicians should offer SBRT as an effective option for recurrent metastatic bone tumors especially involving the spinal vertebrae.