Local Failure Rate Research Articles

STEREOTACTIC BODY RADIOTHERAPY (SBRT) FOR SACRAL METASTASES: DEVIATION FROM RECOMMENDED TARGET VOLUME DELINEATION PREDICTS HIGHER RISK OF LOCAL FAILURE

Abstract Report outcomes after sacrum SBRT, focusing on the impact of contouring deviation on local failure (LF) risk, with an aim to validate the contouring consensus guidelines. METHODS/MATERIALS: Patients who underwent sacral SBRT from 2010- 2021 were identified from a prospectively maintained institutional database. Primary outcomes were magnetic resonance-based LF and vertebral compression fracture (VCF). RESULTS: A total of 215 treated sacral segments in 112 patients were reviewed. Most segments were treated with 30 Gy/4 fractions (51%), 24 Gy/2 fractions (31%), or 30 Gy/5 fractions (10%). Thirty-one percent of segments were of radioresistant histology (gastrointestinal, kidney, melanoma, sarcoma, or thyroid primary), and 51% had extraosseous disease. Sixteen percent of segments were under-contoured per consensus guidelines. The cumulative incidence of LF was 18.4% (95% CI 13.5-24.0) at 12-months and 23.1% (95% CI 17.6-29.0) at 24-months. On multivariate analysis (MVA), under- contouring (HR 2.4, 95% CI 1.3-4.7, p=0.008), radioresistant histology (HR 2.4, 95% CI 1,4-4.1, p=0.001), and extraosseous extension (HR 2.5, 95% CI 1.3-4.7, p=0.005) were predictors of increased risk of LF. The LF rates at 12/24-months were 15.1%/18.8% for segments contoured per guideline versus 31.4%/40.0% for those under-contoured. The cumulative incidence of VCF was 7.1% (95% CI 4.1-11.1) at 12-months and 12.3% (95% CI 8.2-17.2) at 24-months. On MVA, female gender predicted increased VCF risk (HR 2.3, 95% CI 1.1-5.2, p=0.04). CONCLUSIONS: Sacral SBRT is associated with high rates of efficacy and an acceptable VCF risk. Adherence to target volume delineation consensus guidelines reduces the risk of LF.

Predictors of pathologic fracture and local recurrence following stereotactic body radiation therapy to 505 non-spine bone metastases

PurposeStereotactic Body Radiation Therapy (SBRT) is increasingly applied to treat non-spine bone metastases (NSBM) though data remains limited on this approach. In this retrospective study, we report outcomes and predictors of local failure (LF) and pathological fracture (PF) post-SBRT for NSBM using a mature single-institution database. MethodsPatients with NSBM treated with SBRT between 2011 and 2021 were identified. The primary objective was to assess the rates of radiographic LF. Secondary objectives were to assess the rates of in-field PF, overall survival (OS), and late grade ≥ 3 toxicity. Competing risks analysis was used to assess rates of LF and PF. Univariable regression and multivariable regression (MVR) were performed to investigate predictors of LF and PF. ResultsA total of 373 patients with 505 NSBM were included in this study. Median follow-up was 26.5 months. The cumulative incidence of LF at 6, 12, and 24 months were 5.7%, 7.9%, and 12.6%, respectively. The cumulative incidence of PF at 6, 12, and 24 months were 3.8%, 6.1%, and 10.9%, respectively. Lytic NSBM (HR = 2.18; p < 0.01), a lower biologically effective dose (HR = 1.11 per 5 Gy10 decrease; p = 0.04), and a PTV ≥ 54 cc (HR = 4.32; p < 0.01) predicted for a higher risk of LF on MVR. Lytic NSBM (HR = 3.43; p < 0.01), mixed (lytic/sclerotic) lesions (HR = 2.70; p = 0.04), and rib metastases (HR = 2.68; p < 0.01) predicted for a higher risk of PF on MVR. ConclusionSBRT is an effective modality to treat NSBM with high rates of radiographic local control with an acceptable rate of PF. We identify predictors of both LF and PF that can serve to inform practice and trial design.

Let's make size not matter: tumor control and toxicity outcomes of hypofractionated Gamma Knife radiosurgery for large brain metastases.

Management of patients with large brain metastases poses a clinical challenge, with poor local control and high risk of adverse radiation events when treated with single-fraction stereotactic radiosurgery (SF-SRS). Hypofractionated SRS (HF-SRS) may be considered, but clinical data remains limited, particularly with Gamma Knife (GK) radiosurgery. We report our experience with GK to deliver mask-based HF-SRS to brain metastases greater than 10cc in volume and present our control and toxicity outcomes. Patients who received hypofractionated GK radiosurgery (HF-GKRS) for the treatment of brain metastases greater than 10cc between January 2017 and June 2022 were retrospectively identified. Local failure (LF) and adverse radiation events of CTCAE grade 2 or higher (ARE) were identified. Clinical, treatment, and radiological information was collected to identify parameters associated with clinical outcomes. Ninety lesions (in 78 patients) greater than 10cc were identified. The median gross tumor volume was 16.0cc (range 10.1-56.0cc). Prior surgical resection was performed on 49 lesions (54.4%). Six- and 12-month LF rates were 7.3% and 17.6%; comparable ARE rates were 1.9% and 6.5%. In multivariate analysis, tumor volume larger than 33.5cc (p = 0.029) and radioresistant histology (p = 0.047) were associated with increased risk of LF (p = 0.018). Target volume was not associated with increased risk of ARE (p = 0.511). We present our institutional experience treating large brain metastases using mask-based HF-GKRS, representing one of the largest studies implementing this platform and technique. Our LF and ARE compare favorably with the literature, suggesting that target volumes less than 33.5cc demonstrate excellent control rates with low ARE. Further investigation is needed to optimize treatment technique for larger tumors.

Risk-adjusted chemoradiation according to human papilloma viral status for anal cancer: a pilot study.

HPV-associated or positive (HPV+) anal cancer patients may have better outcome compared to those with HPV negative (HPV-) disease. We report a planned interim analysis of a prospective registry study that tailors chemoradiation (CRT) for anal cancer according to HPV status. HPV+ patients received de-escalated radiation doses of 45, 50.4 and 55.8 Gy, while HPV- received 50.4, 55.8 and 63 Gy for T1, T2 and T3/T4 disease respectively. Chemotherapy consisted of a single dose of mitomycin-C and oral capecitabine on days of RT. All patients were planned by VMAT following CT, PET/CT and MR simulation. This cohort (n = 24) had a minimum 24-month follow-up. Disease free survival (DFS) and local failure rates (LFR) were compared with 180 patients managed by standard CRT (2 cycles of mitomycin-C and 5-fluorouracil, radiation doses 50.4-63 Gy based on T-category) from 2011-2018. Propensity score comparison was performed using a retrospective to prospective 2 to 1 match based on tumor size and N-category. In the HPV+ cohort (n = 20), there were 2 local failures. Two of 4 HPV- patients failed locally. The 30-month DFS and LFR were 79% and 17% respectively. Similar DFS and LFR were observed in the retrospective (80% and 15% respectively) and matched patients (76% and 16% respectively). No grade ≥3 neutropenia and febrile neutropenia were observed in the registry cohort whereas 19% and 14% respectively were seen in the retrospective patients. De-escalation of CRT for HPV+ anal cancer may result in decreased acute toxicities and similar cancer outcomes compared to standard CRT.

Postoperative Management of Recurrence After Radiosurgery and Surgical Resection for Brain Metastases and Predicting Benefit From Adjuvant Radiation

Stereotactic radiosurgery (SRS) is often used as upfront treatment for brain metastases. Progression or radionecrosis after SRS is common and can prompt resection. However, postoperative management strategies after resection for SRS failure vary widely, and no standard practice has been established. In this approved study, we retrospectively reviewed patients who received SRS for a brain metastasis followed by resection of the same lesion. We extracted patient-, disease-, and treatment-related variables and information on disease-related outcomes. Univariate and multivariate analyses of clinicopathologic variables were used to create a model to predict factors associated with local failure (LF). A total of 225 patients with brain metastases treated with SRS from 2009 to 2017 followed by surgical resection were identified. Overall, 65% of cases had gross total resection (GTR) on postoperative imaging review. Twenty-one patients (9.3%) received adjuvant radiation therapy to the surgical cavity, and 204 (90.7%) were observed. Of these 204 patients, 118 had GTR with evidence of tumor within the pathology specimen. With a median follow-up of 13 months after resection, 47 patients (40%) developed LF after surgery. After salvage resection of a brain metastasis initially treated with SRS, the observed LF rate was 40% among those who had a GTR and evidence of tumor on pathologic examination. This LF rate is sufficiently high that adjuvant radiation to the surgical bed after salvage resection should be considered in these cases when there is tumor in the pathology, even after a GTR.

Efficacy of a Second Course of Radiation for Patients With Metachronous Hepatocellular Carcinoma

Liver-directed radiation therapy is an effective treatment for hepatocellular carcinoma (HCC), but metachronous lesions develop outside the irradiated field in >50% of patients. We hypothesized that irradiation of these new lesions would produce an outcome like that of patients receiving a first course (C1) of treatment. We included patients with HCC who received a second course (C2) of radiation therapy >1 month after C1. Toxicity was defined as Child-Pugh score increase ≥2 within 6 months posttreatment (binary model) and as the change in albumin-bilirubin during the year after treatment (longitudinal model). Overall survival (OS) and local failure (LF) were captured at the patient and lesion level, respectively; both were summarized with Kaplan-Meier estimates. Predictors of toxicity and OS were assessed using generalized linear mixed and Cox regression models, respectively. Of 340 patients with HCC, 47 underwent irradiation for metachronous HCC, receiving similar prescription dose in C1/C2. Median follow-up was 17 months after C1 and 15 months after C2. Twenty-two percent of patients experienced toxicity after C1, and 25% experienced toxicity after C2. Worse baseline albumin-bilirubin predicted toxicity in both binary (odds ratio, 2.40; 95% CI, 1.46-3.94; P=.0005) and longitudinal models (P < .005). Two-year LF rate was 11.2% after C1 and 8.3% after C2; tumor dose (hazard ratio [HR], 0.982; 95% CI, 0.969-0.995; P=.007) and tumor size (HR, 1.135; 95% CI, 1.068-1.206; P < .005) predicted LF. Two-year OS was 46.0% after C1 and 42.6% after C2; tumor dose (HR, 0.986; 95% CI, 0.979-0.992; P < .005) and tumor size (HR, 1.049; 95% CI, 1.010-1.088; P=.0124) predicted OS. Reirradiation was not associated with toxicity (P > .7), LF (P=.79), or OS (P=.39). In this largest series in the Western hemisphere, we demonstrate that irradiation for metachronous HCC offers low rates of LF with acceptable toxicity and OS like that of patients receiving a C1. These findings support judicious selection of patients for reirradiation in metachronous HCC.

Predictive value of the deltoid tuberosity index for assessing the risk of screw cut-out

Abstract Background Reconstruction of the proximal humerus with a locking plate is often the first surgical approach for proximal humerus fractures. Screw cut-out is a common complication and is relevant in osteoporotic bone of older adults. The Deltoid Tuberosity Index (DTI) is an indirect measure for assessing local bone quality and failure rate before surgery, providing important information for surgical planning. This was the first independent, large-sample retrospective analysis of the correlation between local bone density, indirectly measured through the DTI, and screw cut-out. Methods In total, 306 cases of proximal humerus fractures treated with the PHILOS plate (DePuy Synthes, Oberdorf, Switzerland) were retrospectively analyzed. The DTI was measured on anteroposterior x‑rays. The primary endpoint was screw cut-out defined as the intra-articular position of at least one screw associated with a reduction loss after surgery. Results The mean clinical follow-up was 935 days. The DTI varied from 1.10 to 2.28 (average: 1.45). Screw cut-out occurred on average in 8% of the cases and was positively correlated with a DTI of ≤ 1.44 (p = 0.003). However, the rate of cut-out and correlation with DTI varied widely according to age group: for ages 65–80 years, a DTI of ≤ 1.44 increased the cut-out rate from 0% to 17% (p = 0.02); in younger ages (&lt; 65 years) the DTI did not correlate with cut-out and in the oldest group (&gt; 80 years) cut-out rates were high (17–20%) independently of the DTI. Conclusion We confirm the correlation between a DTI of ≤ 1.44 and screw cut-out. High-risk groups for screw cut-out are patients over 65 years with a DTI of ≤ 1.44 or any patient older than 80 years. Applying the DTI in the age group of 65–80 years offers relevant information for surgical planning in the trauma setting via a fast, cheap, and easy-to-use tool. Level of Evidence: Level 3, Retrospective Cohort Study.

Intensity-Modulated Radiation Therapy for Early-Stage Squamous Cell Carcinoma of the Glottic Larynx: A Systematic Review and Meta-Analysis

Early-stage squamous cell carcinoma of the glottic larynx is commonly treated with 2-dimensional or 3-dimensional conventional radiation therapy (CRT). Despite its use in other head and neck cancers, intensity-modulated radiation therapy (IMRT) remains controversial in this patient population. A systematic review was performed by querying 3 databases (Pubmed, Embase, Web of Science) for articles published between December 1, 2000 and September 2, 2022. Included studies reported outcomes in at least 10 patients treated with IMRT for early-stage glottic cancer. Data were extracted and reported following PRISMA standards. Pooled outcomes were estimated using random-effects models. Primary outcome was the rate of local failure (LF) following IMRT. Secondary outcomes included rates of regional failure (RF) following IMRT and rates of LF and RF following CRT. A total of 15 studies (14 retrospective, 1 prospective) consisting of 2083 patients were identified. IMRT was used in 873 patients (64% T1, 28% T2). Multiple treatment (partial larynx, single vocal cord carotid sparing) and image-guided radiation therapy techniques were used. The pooled crude rate of LF was 7.6% (95% confidence inverval [CI], 3.6%-11.5%) and actuarial LF rates at 3 and 5 years were 6.3% (95% CI, 2.2%-10.3%) and 9.0% (95% CI, 4.4%-13.5%), respectively. The pooled crude rate of RF after IMRT was 1.5% (95% CI, 0.5%-2.5%). On metaregression analysis, increased rate of LF was significantly associated with T2 disease (P < .001) and grade 2 to 3 histology (P < .001). Treatment with CRT was reported in 738 patients (76% T1, 22% T2). Among the studies reporting outcomes of both modalities, there was no significant difference in LF (log odds ratio; P=.12) or RF (log odds ratio; P=.58) between IMRT or CRT. In patients with early-stage glottic cancer, retrospective data suggests local and regional control are similar for patients treated with IMRT and CRT. Additional prospective studies with uniform methods of volume delineation and image guidance are needed to confirm the efficacy of IMRT.

Optimized radiotherapy treatment strategy for early glottic carcinoma.

The local control rates of T1 bulky and T2 glottic carcinoma treated via radiation therapy alone are unsatisfactory; thus, we aimed to evaluate the efficacy and safety of our treatment protocol for early glottic carcinoma. Patients with early glottic squamous cell carcinoma treated via radiation therapy from January 2007 to November 2019 were reviewed. Patients were treated with: 63-67.5 Gy/28-30 fractions of radiation therapy alone for T1 non-bulky; concurrent chemoradiotherapy with S-1 and 60 Gy/30 fractions for T1 bulky and T2 favorable; and concurrent chemoradiotherapy with high-dose cisplatin and 66-70 Gy/33-35 fractions for T2 unfavorable glottic carcinoma. Local failure rates were estimated using the cumulative incidence function, overall and disease specific survival rates were estimated using Kaplan-Meier analysis, and adverse events were evaluated. Eighty patients were analyzed; the median age was 69.5 (range, 26-90) years, the median follow-up time for survivors was 40.1 (range, 1.9-128.4) months, and the 3-year local failure, disease specific survival, and overall survival rates were 5.8%, 98.3%, and 94.4%, respectively. In T1 bulky and T2 cases, the local failure rate was significantly lower in the concurrent chemoradiotherapy than in the radiation therapy alone group. Grade 3 acute dermatitis and mucositis were noted in nine and four patients, respectively. There were no acute adverse events of Grade 4 or higher, or late adverse events of Grade 2 or higher. The treatment protocol was effective and well-tolerated; thus, the efficacy of concurrent chemoradiotherapy was suggested in T1 bulky and T2 cases.

Pathologic Complete Response and Clinical Outcomes in Patients With Localized Soft Tissue Sarcoma Treated With Neoadjuvant Chemoradiotherapy or Radiotherapy

Pathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS). We sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630. RTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS. One hundred forty-three eligible patients from RTOG 0630 (n = 79) and RTOG 9514 (n = 64) were included in this ancillary analysis of pCR and 79 patients from RTOG 0630 were evaluated for long-term outcomes. Patients in trial 9514 received CT interdigitated with RT, whereas those in trial 0630 received preoperative RT alone. Overall and disease-free survival (OS and DFS) rates were estimated by the Kaplan-Meier method. Hazard ratios (HRs) and P values were estimated by multivariable Cox model stratified by study, where possible; otherwise, P values were calculated by stratified log-rank test. Analysis took place between December 14, 2016, to April 13, 2017. Overall there were 42 (53.2%) men; 68 (86.1%) were white; with a mean (SD) age of 59.6 (14.5) years. For RTOG 0630, at median follow-up of 6.0 years, there was 1 new in-field recurrence and 1 new distant failure since the initial report. From both studies, 123 patients were evaluable for pCR: 14 of 51 (27.5%) in trial 9514 and 14 of 72 (19.4%) in trial 0630 had pCR. Five-year OS was 100% for patients with pCR vs 76.5% (95% CI, 62.3%-90.8%) and 56.4% (95% CI, 43.3%-69.5%) for patients with less than pCR in trials 9514 and 0630, respectively. Overall, pCR was associated with improved OS (P = .01) and DFS (HR, 4.91; 95% CI, 1.51-15.93; P = .008) relative to less than pCR. Five-year local failure rate was 0% in patients with pCR vs 11.7% (95% CI, 3.6%-25.1%) and 9.1% (95% CI, 3.3%-18.5%) for patients with less than pCR in 9514 and 0630, respectively. Histologic types other than leiomyosarcoma, liposarcoma, and myxofibrosarcoma were associated with worse OS (HR, 2.24; 95% CI, 1.12-4.45). This ancillary analysis of 2 nonrandomized clinical trials found that pCR was associated with improved survival in patients with STS and should be considered as a prognostic factor of clinical outcomes for future studies. ClinicalTrials.gov Identifiers: RTOG 0630 (NCT00589121); RTOG 9514 (NCT00002791).

Phase 1 Dose Escalation Study of SBRT Using 3 Fractions for Locally Advanced Pancreatic Cancer

The optimal dose and fractionation of stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) have not been defined. Single-fraction SBRT was associated with more gastrointestinal toxicity, so 5-fraction regimens have become more commonly employed. We aimed to determine the safety and maximally tolerated dose of 3-fraction SBRT for LAPC. Two parallel phase 1 dose escalation trials were conducted from 2016 to 2019 at Memorial Sloan Kettering Cancer Center and University of Colorado. Patients with histologically confirmed LAPC without distant progression after at least 2 months of induction chemotherapy were eligible. Patients received 3-fraction linear accelerator-based SBRT at 3 dose levels, 27, 30, and 33 Gy, following a modified 3+3 design. Dose-limiting toxicity, defined as grade ≥3 gastrointestinal toxicity within 90 days, was scored by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The secondary endpoints included cumulative incidence of local failure (LF) and distant metastasis (DM), as well as progression-free and overall survival PFS and OS, respectively, toxicity, and quality of life (QoL) using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and the pancreatic cancer-specific QLQ-PAN26 questionnaire. Twenty-four consecutive patients were enrolled (27 Gy: 9, 30 Gy: 8, 33 Gy: 7). The median (range) age was 67 (52-79) years, and 12 (50%) had a head/uncinate tumor location, with a median tumor size of 3.8 (1.1-11) cm and CA19-9 of 60 (1-4880) U/mL. All received chemotherapy for a median of 4 (1.4-10) months. There were no grade ≥3 toxicities. Two-year rates (95% confidence interval) of LF, DM, PFS, and OS were 31.7% (8.6%-54.8%), 70.2% (49.7%-90.8%), 20.8% (4.6%-37.1%), and 29.2% (11.0%-47.4%), respectively. Three- and 6-month QoL assessment showed no detriment. For select patients with LAPC, dose escalation to 33 Gy in 3 fractions resulted in no dose-limiting toxicities, no detriments to QoL, and disease outcomes comparable with conventional RT. Further exploration of SBRT schemes to maximize tumor control while enabling efficient integration with systemic therapy is warranted.

Hypofractionated stereotactic radiosurgery (HSRS) as a salvage treatment for brain metastases failing prior stereotactic radiosurgery (SRS)

Various treatment options exist to salvage stereotactic radiosurgery (SRS) failures for brain metastases, including repeat SRS and hypofractionated SRS (HSRS). Our objective was to report outcomes specific to salvage HSRS for brain metastases that failed prior HSRS/SRS. Patients treated with HSRS to salvage local failures (LF) following initial HSRS/SRS, between July 2010 and April 2020, were retrospectively reviewed. The primary outcomes were the rates of LF, radiation necrosis (RN), and symptomatic radiation necrosis (SRN). Univariable (UVA) and multivariable (MVA) analyses using competing risk regression were performed to identify predictive factors for each endpoint. 120 Metastases in 91 patients were identified. The median clinical follow up was 13.4 months (range 1.1-111.1), and the median interval between SRS courses was 13.1 months (range 3.0-56.5). 115 metastases were salvaged with 20-35Gy in 5 fractions and the remaining five with a total dose ranging from 20 to 24Gy in 3-fractions. 67 targets (56%) were postoperative cavities. The median re-treatment target volume and biological effective dose (BED10) was 9.5cc and 37.5Gy, respectively. The 6- and 12- month LF rates were 18.9% and 27.7%, for RN 13% and 15.6%, and for SRN were 6.1% and 7.0%, respectively. MVA identified larger re-irradiation volume (hazard ratio [HR] 1.02, p = 0.04) and shorter interval between radiosurgery courses (HR 0.93, p < 0.001) as predictors of LF. Treatment of an intact target was associated with a higher risk of RN (HR 2.29, p = 0.04). Salvage HSRS results in high local control rates and toxicity rates that compare favorably to thosesingle fraction SRS re-irradiationexperiences reported in the literature.

Linac-based stereotactic salvage reirradiation for intraprostatic prostate cancer recurrence: toxicity and outcomes

BackgroundThe rates of local failure after curative radiotherapy for prostate cancer (PC) remain high despite more accurate locoregional treatments available, with one third of patients experiencing biochemical failure and clinical relapse occurring in 30–47% of cases. Today, androgen deprivation therapy (ADT) is the treatment of choice in this setting, but with not negligible toxicity and low effects on local disease. Therefore, the treatment of intraprostatic PC recurrence represents a challenge for radiation oncologists. Prostate reirradiation (Re-I) might be a therapeutic possibility. We present our series of patients treated with salvage stereotactic Re‑I for intraprostatic recurrence of PC after radical radiotherapy, with the aim of evaluating feasibility and safety of linac-based prostate Re‑I.Materials and methodsWe retrospectively evaluated toxicities and outcomes of patients who underwent salvage reirradiation using volumetric modulated arc therapy (VMAT) for intraprostatic PC recurrence. Inclusion criteria were age ≥ 18 years, histologically proven diagnosis of PC, salvage Re‑I for intraprostatic recurrence after primary radiotherapy for PC with curative intent, concurrent/adjuvant ADT with stereotactic body radiation therapy (SBRT) allowed, performance status ECOG 0–2, restaging choline/PSMA-PET/TC and prostate MRI after biochemical recurrence, and signed informed consent.ResultsFrom January 2019 to April 2022, 20 patients were recruited. Median follow-up was 26.7 months (range 7–50). After SBRT, no patients were lost at follow-up and all are still alive. One- and 2‑year progression free survival (PFS) was 100% and 81.5%, respectively, while 2‑year biochemical progression-free survival (bFFS) was 88.9%. Four patients (20%) experienced locoregional lymph node progression and were treated with a further course of SBRT. Prostate reirradiation allowed the ADT start to be postponed for 12–39 months. Re‑I was well tolerated by all patients and none discontinued the treatment. No cases of ≥ G3 genitourinary (GU) or gastrointestinal (GI) toxicity were reported. Seven (35%) and 2 (10%) patients experienced acute G1 and G2 GU toxicity, respectively. Late GU toxicity was recorded in 10 (50%) patients, including 8 (40%) G1 and 2 (10%) G2. ADT-related side effects were found in 7 patients (hot flashes and asthenia).ConclusionLinac-based SBRT is a safe technique for performing Re‑I for intraprostatic recurrence after primary curative radiotherapy for PC. Future prospective, randomized studies are desirable to better understand the effectiveness of reirradiation and the still open questions in this field.

Outcomes from a 3-fraction high-dose-rate brachytherapy regimen for patients with cervical cancer

PURPOSETo estimate local control, survival, and toxicity associated with a 3-fraction (3F) image-guided brachytherapy (IGBT) regimen compared to longer fraction (LF) for cervical cancer. METHODS150 patients treated between 2015-2020 with 3F (24Gy in 3 fractions) or LF (28...30 Gy in 4-5 fractions) were reviewed. The primary outcome was 2-year local failure. We compared overall survival (OS), disease-free survival (DFS), hospitalizations, and toxicity. RESULTSThere were 32 patients in the 3F group and 118 in the LF group, with a median follow up of 22 months. The 3F had worse performance status (p = 0.01) but otherwise similar characteristics. The 2-year local failure rate was 3.6% (95% CI 0%, 10.6%) for 3F, and 7.5% (95% CI 2.4%, 12.6%) for LF. The univariable hazard ratio (HR) for local failure for 3F was 0.43 (0.05, 3.43; p = 0.43). Moreover, 2 of 32 (6.3%) 3F patients experienced Grade ...3 toxicity compared to 7 of 118 (5.9%) LF patients (p = 1.0), with no difference in hospitalization within 2 years (p = 0.66) and no treatment-related deaths. CONCLUSIONSLocal control was excellent, with long term survival and toxicity similar between the groups. These findings support consideration of 3F.

Sinonasal adenocarcinomas: Retrospective analysis from an oncology center

Introduction and objectivesSinonasal adenocarcinomas are rare and heterogeneous tumors and for this reason remain understudied. Our purpose is to analyze clinical presentation, outcomes and factors affecting survival of patients with sinonasal adenocarcinomas, treated at our institution. Material and methodsRetrospective review of clinical records of patients with sinonasal adenocarcinoma, treated at a tertiary oncology institution (January 2010 to December 2019). ResultsSixty patients diagnosed with adenocarcinoma were included, with male preponderance (54.90%) and a mean age of 57.5±14.9 years. Adenocarcinoma was the most frequent type of sinonasal cancer, contrary to previous reports from our institution. In most patients, it was detected at an advanced disease stage, significantly decreasing their survival rate when compared to patients diagnosed at initial stages (p<0.029). Intestinal type adenocarcinoma was established in 47 patients, the most frequent being the colonic subtype (24%). Tumors with good/moderate histologic differentiation presented a survival advantage over those that were poorly differentiated (p=0.043). The most common treatment modality was surgery followed by radiotherapy. Endoscopic resection was performed in 53% of the patients and an external approach was used in 40% of the patients. Estimated overall survival rates at 3 and 5-years were 64% and 53%, respectively, and cancer specific survival 72% and 65%, for the same period. Recurrence rate was 32% and occurred mainly locally. Disease Free Survival rate was 71% at 3 years and 65% at 5 years. ConclusionsDespite being the most common sinonasal malignancy in our sample, in contrast to other series, sinonasal adenocarcinomas are still rare tumors with a substantial local failure rate of around 30%. Advanced stage at diagnosis and histologic differentiation grade negatively affected prognosis of these tumors.

A Comparison of Single Fraction and Multi Fraction Radiosurgery on the Gamma Knife ICON: A Single Institution Review

PurposeBrain metastases are a common development in patients with malignant solid tumors. Stereotactic radiosurgery (SRS) has a long track record of effectively and safely treating these patients, with some limitations to the use of single fraction SRS based on size and volume. In this study, we reviewed outcomes of patients treated using SRS and fractionated SRS (fSRS) to compare predictors and outcomes of those treatments. Methods and MaterialsTwo hundred patients treated with SRS or fSRS for intact brain metastases were included. We tabulated baseline characteristics and performed a logistic regression to identify predictors of fSRS. Cox regression was used to identify predictors of survival. Kaplan-Meier analysis was used to calculate survival, local failure, and distant failure rates. A receiver operating characteristic curve was generated to determine timepoint from planning to treatment associated with local failure. ResultsThe only predictor of fSRS was tumor volume >2.061 cm3. There was no difference in local failure, toxicity, or survival by fractionation of biologically effective dose. Predictors of worse survival were age, extracranial disease, history of whole brain radiation therapy, and volume. Receiver operating characteristic analysis identified 10 days as potential factor in local failure. At 1 year, local control was 96.48 and 76.92% for those patients treated before or after that interval, respectively (P = .0005). ConclusionsFractionated SRS is a safe and effective alternative for patients with larger volume tumors not suitable for single fraction SRS. Care should be taken to treat these patients expeditiously as a delay was shown to affect local control in this study.

Impact of depth of invasion on local recurrence in R0 resected node-negative oral tongue squamous cell carcinoma.

This study evaluates the impact of depth of invasion (DOI) on local recurrence (LR) in node-negative oral tongue squamous cell carcinoma (SCC). Fifty-one patients were retrospectively reviewed from an institutional database. Patients were evaluated for local control (LC). Cox-proportional hazards modeling was used to calculate hazard ratios. There were 84.3% T1/2 and 15.7% T3/4 classification tumors. The 3-year overall survival rate was 97.9%. Local failure rate was 5.7% with a 3-year LC of 93.6%. On Univariate analysis, increased hazard of LR was noted with each unit increase in DOI (HR 1.40, 95% CI 1.07-1.83, p=0.014). Age, sex, T classification, margins ≥5 mm, lymphovascular invasion (LVI) and perineural invasion (PNI), and adjuvant treatment were not associated with LR. On Multivariate analysis, adjusting for age and adjuvant treatment, results for DOI remained significant (aHR 1.46, 95% CI 1.08-1.98, p=0.013). On evaluation of our institutional dataset increasing DOI was associated with increased hazard of local recurrence with oral tongue SCC.

Therapeutic Implications of TGF-β Pathway in Desmoid Tumor Based on Comprehensive Molecular Profiling and Clinicopathological Properties

(1) Background: Desmoid tumors have a relatively high local failure rate after primary treatment using surgery and/or radiotherapy. Moreover, desmoid tumors recur at the primary site for many patients. An effective therapeutic strategy for the desmoid tumor is needed to maintain quality of life and prolong survival. (2) Method: First of all, we collected desmoid tumor tissues and investigated the status of protein expression for beta-catenin and alpha-SMA through immunohistochemistry. Then, we performed targeted sequencing and whole RNA sequencing. To compare the data with other cancer types, we used NGS data from sarcoma patients at Yonsei Cancer Center (YCC-sarcoma cohort, n = 48) and The Cancer Genome Atlas (TCGA, n = 9235). Secondly, we established the novel patient-derived preclinical models (n = 2) for the validation of treatment strategy. The same gene alteration of primary tissue was demonstrated. (3) Results: We discovered specific gene sets related to the TGF-β signaling pathway. Moreover, we selected the combination treatment comprising TGF-β inhibitor, vactosertib, and imatinib. In screening for the anti-proliferation effect, the combination treatment of TGF-β inhibitor was more effective for tumor suppression than monotherapy. (4) Conclusion: We found preclinical indications that TGF-β inhibitors could prove useful as a potential treatment for patients with desmoid tumors. Moreover, we could find some examples in clinical trials.

Role of postoperative radiotherapy in resected adenoid cystic carcinoma of the head and neck

PurposeAlthough postoperative radiotherapy (PORT) is demonstrably effective in local control of head and neck adenoid cystic carcinoma (HNACC), its application is controversial and the subset of patients who would benefit most from PORT is unknown. Herein, we analyzed the data of HNACC patients to clarify the role of PORT.MethodsWe retrospectively reviewed 187 patients with nonmetastatic HNACC who underwent surgical resection between 2005 and 2019. The study endpoints were locoregional failure-free survival (LRFFS), progression-free survival (PFS), and overall survival (OS). Subgroup analysis and recursive partitioning analysis (RPA) were performed to identify patients most likely to benefit from PORT.ResultsWith a median follow-up of 84.7 months, the 5-year LRFFS, PFS, and OS were 70.0%, 52.6%, and 86.4%, respectively. Survival was significantly shorter in patients who experienced local failure than in those who did not (5-year OS: 88.1% vs. 80.5%, P = 0.001). The local failure rate was significantly lower in patients who underwent PORT (16.9% vs. 31.0%, P = 0.021), despite the high frequency of adverse factors. Especially, significant decreases in local failure and similar OS rates could be obtained after PORT among patients with positive margins, T2-4 stage disease, and minor salivary gland tumors. The RPA model for PFS categorized patients into four groups according to three prognostic factors (T-stage, location, and sex). The RPA model for LRFFS and OS suggested three groups based on two factors (T-stage, margin for LRFFS; T-stage, grade 3 for OS).ConclusionPORT could prevent dismal survival, while significantly reducing local failures in high-risk HNACC patients.

RADT-35. A PROSPECTIVE REGISTRY STUDY OF 68GA-DOTATATE PET INCORPORATION INTO TREATMENT PLANNING OF INTRACRANIAL MENINGIOMAS

Abstract Introduction The current standard for meningioma radiation planning involves MRI-based image guidance. SSTR ligands such as 68Ga-DOTATATE are being explored for meningioma radiotherapy treatment planning due to universal expression of somatostatin receptor 1/2 in meningioma tissue. We hypothesize that 68Ga-DOTATATE PET utilization can reduce the risk of local failure (LF) through precise radiation planning and may also suggest that patients who have local PET avidity after a perceived GTR may be poor observation candidates. METHODS A single institution prospective registry study was created and included intracranial meningioma patients who received a 68Ga-DOTATATE PET scan to assist with radiation oncologist decision-making. These were ordered for all meningioma patients as a departmental standard. Patients who received a PET scan from 1/1/2018-2/25/2022 were eligible for inclusion. RESULTS 60 patients were treated in this prospective registry. 22%, 72%, and 7% were World Health Organization (WHO) high, intermediate, and low-risk, respectively. After completing their PET scan, 48, 11, and 1 patient(s) proceeded with RT, observation, or redo craniotomy. The median follow up was 16 months (IQR 8.3-23.1). 3 patients (5%) experienced LF between 9.2-28.5 months after diagnosis. 2 patients with LF had PET-avid disease in their post-operative cavity and elected for observation prior to recurrence, and 1 high-risk patient with multifocal disease experienced LF 2 years after a second radiation course and multiple previous recurrences. LF rates after radiation were 0%, 0%, and 8% in the low, intermediate, and high-risk cohorts, respectively. There were no Grade 3 or higher toxicities attributed to PET-guided radiation. CONCLUSION This is the largest known population of intracranial meningioma patients followed by physicians who utilized 68Ga-DOTATATE PET guided therapy. Only 1 patient experienced LF after receiving PET-guided radiation therapy, likely due to a radioresistant histology. Incorporating 68Ga-DOTATATE PET into future trials may assist with clinician decision-making and improve patient outcomes.