Actuarial Rate Research Articles

Radiosurgery for Primary and Metastatic CNS Malignancies in the Pediatric Population

<h3>Purpose/Objective(s)</h3> Safety and efficacy of stereotactic radiosurgery (SRS) are not well described for pediatric patients. This study presents disease control and toxicity outcomes after SRS for malignant CNS lesions in pediatric patients. <h3>Materials/Methods</h3> Retrospective chart review was performed for 31 pediatric patients treated at a single institution with a non-invasive stereotactic radiosurgery instrument for primary or metastatic CNS malignancies between 2000-2020. Analyses were performed with descriptive statistics, Kaplan-Meier, and proportional hazards modeling. <h3>Results</h3> Twenty-five patients were treated with SRS for focal recurrences of primary CNS malignancies, 1 patient was treated in the early adjuvant setting after initial resection, and 5 patients were treated for brain metastases. Primary CNS histologies included ependymoma (n=14), glioma (n=4), medulloblastoma (n=2), and meningioma (n=2). 65% were WHO grade 3 or 4 at the time of diagnosis. Brain metastases were from non-germinomatous germ cell tumors (n=3), papillary thyroid cancer (n=1), and neuroblastoma (n=1). 71% of patients had prior involved-field external beam radiation to the brain (median dose 59.4 Gy in 33 fractions). Median age at SRS was 14 years (range 4-21). SRS was predominantly performed in a single fraction (median dose 17 Gy, range 15-20) to a total of 42 targets among 29 patients, with a median total gross target volume (GTV) of 1.3 cc. Two patients underwent fractionated radiosurgery to 30 Gy in 5 fractions for larger brain metastases (GTVs 8.5 cc & 23.2 cc). Median follow up after SRS was 44 months (interquartile range 20-72). The 3-year actuarial rates of local control, intracranial progression-free survival, and overall survival after SRS were 77.6%, 33.3%, and 74.6%, respectively. 9 patients (29%) had no evidence of intracranial disease after SRS at a median follow up of 39 months. 6 patients (19%) developed local recurrence at a median of 13 months after SRS. 16 patients (52%) developed distant brain recurrence without local failure at a median of 9 months after SRS. Among primary CNS tumors, there was no significant association of histology, grade, or dose with disease control outcomes on univariate analysis. All patients with subsequent CNS recurrence after SRS underwent salvage therapy, including additional radiosurgery (36%), systemic therapy (23%), resection (9%), or combined modality treatment (32%). In total, 4 patients developed CTCAE grade 2-3 toxicity from SRS, all of which were related to radiation treatment effect and occurred within 1 year of SRS. 2 patients received steroids alone, and 2 underwent invasive procedures (1 shunt revision, 1 resection of nonviable tumor). <h3>Conclusion</h3> SRS for malignant CNS lesions in the pediatric population provides effective local control and is generally well-tolerated. Although there remains a substantial risk of distant CNS failures, all patients were able to receive additional salvage therapy after SRS.

Radiation therapy for primary orbital and ocular adnexal lymphoma

ObjectiveTo report the efficacy and toxicity of External beam Radiotherapy (EBRT) as a sole treatment for MALT and Follicular Primary Orbital and Ocular adnexal Lymphoma (POOAL) MethodsRetrospective review of all POOAL patients treated with EBRT utilizing megavoltage photon or electron beam radiotherapy between 2003 and 2015. Patient demographics, tumour extent and pathology, radiotherapy techniques, and treatment outcomes were reviewed. The actuarial rates of tumour control and radiation toxicities were calculated using Kaplan-Meier estimates. ResultsThis study included 167 tumours, of which MALT lymphoma involved 149 (89 %). The conjunctiva and orbit were equally involved as the predominant site (48 %). Megavoltage photon radiotherapy was used in 60 % of predominantly orbital lymphoma and Electron beam with lens shielding in 77 % of the conjunctival lymphoma. The majority (95 %) were treated with a total dose of 25 Gy in 10 fractions. Local control rate was 98 % (CI: 93–100 %) at 5 years. The long-term RT toxicities included dry eye in 27 eyes (16 %) and cataract in 22 (13 %). None of the patients developed significant structural or functional radiation toxicity. ConclusionExternal Beam Radiotherapy, with lens shielding whenever indicated, at a dose of 20–30 Gy delivered over 10–20 fractions is an efficacious and safe primary treatment option for POOAL lymphoma, with excellent local control and low incidence of late manageable ocular toxicities.

Maintenance tegafur-plus-uracil after adjuvant concurrent chemoradiotherapy may improve outcome for resected oral cavity squamous cell carcinoma with extranodal extension.

ObjectivesTo evaluate whether tegafur-uracil maintenance (UFTm) following postoperation adjuvant cisplatin-based concurrent chemoradiotherapy (CCRT) may reduce distant metastasis in patients with resected oral cavity squamous cell carcinoma (OSCC) with pathologic extranodal extension (pENE+).MethodsA retrospective comparison was conducted between two cohorts of patients with resected pENE+ OSCC who completed adjuvant CCRT between March 2015 and December 2017, including one cohort of a phase II trial using UFTm and a trial-eligible but off-protocol cohort without using UFTm (non-UFTm) after their adjuvant CCRT. The UFTm trial enrolled patients without relapse within 2 months after the end of adjuvant CCRT and administered UFT 400 mg/day for 1 year. Kaplan–Meier methods estimated the actuarial rate of distant metastasis-free (DMF), locoregional control (LRC), event-free survival (EFS), and overall survival (OS).ResultsA total of 103 patients were included in this study, 64 patients in UFTm and 39 patients in non-UFTm. Severe adverse events in UFTm included grade 3 anemia (n = 1, 1.6%) and grade 3 mucositis (n = 1, 1.6%). A total of 40 (62.5%) patients completed the full course of UFTm, while the remaining terminated UFTm earlier due to disease relapse (n = 14, 21.8%), poor compliance (n = 9, 14.1%), and adverse event (n = 1, 1.6%). The median (range) follow-up time of surviving patients was 43 (22–65) months. The outcomes compared between UFTm and non-UFTm were OS (hazard ratio [HR] 0.31 [95% CI: 0.17–0.57], p < 0·001), EFS (0.45 [0.25–0.82], 0.009), LRC (0.45 [0.19–1.05], 0.067), and DMF (0.47 [0.24–0.95], 0.035). Multivariable analysis, adjusted for UFTm, Charlson comorbidity index score 1–3, site of tongue, and number of ENE+ LN ≧4, confirmed better OS (0.29 [0.16–0.54], <0.001) and EFS (0.47 [0.26–0.85], 0.012) in favor of UFTm over non-UFTm. The 2-year DM rate was 25.8% in UFTm and 44.2% in non-UFTm. For relapsed patients in UFTm vs. non-UFTm, the rate of metastasectomy for oligometastasis was 53% vs. 6%, and the OS was 21.0 (95% CI: 17.8–24.1) months vs. 11.0 (9.1–12.8) months (p < 0.001), respectively.ConclusionsUFTm may improve the dismal outcomes of the resected pENE+ OSCC. Further investigations are needed to confirm our observations.

Evaluation of treatment results of stereotactic body radiotherapy for spinal metastases: A single center experience

Aim: To assess oncological outcomes and adverse events of patients receiving single or multi-fraction stereotactic body radiotherapy (SBRT) for spine metastases. &#x0D; Material and Method: Patients with any pathologically proven solid tumor histology who had SBRT to the spine for recurrent or metastatic disease between the years 2010 and 2021 at our department were identified from institutional database. Patient, tumor and treatment characteristics, and follow-up medical records were retrospectively reviewed. Local control (LC) and overall survival (OS) rates were calculated, and adverse events were evaluated.&#x0D; Results: A total of 47 patients were treated to 50 spine metastases. Median age was 53 years for all patients. Histologies included breast cancer (45%), non-small cell lung cancer (NSCLC; 21%), prostate cancer (15%) and other types (19%). Median follow-up was 16 months for all patients. Of 47 patients, six (13%) developed local failure and 15 (32%) died without local failure. One and two-year actuarial LC rates were 90.1% and 83.6%, respectively. One and two-year OS rates were 75.1% and 62.7%, respectively. Twenty-two (47%) patients had pain before SBRT. Fifteen (68%) of them had complete or partial pain response at 3 months after SBRT. Vertebral compression fracture, which was grade 1 in severity according to the Common Terminology Criteria for Adverse Events (CTCAE [v.4.03]), was observed in only one (2%) patient and it occurred 46 months after SBRT. No cases of treatment-related radiation myelopathy or any≥grade 3 RT induced acute or late toxicities occurred. &#x0D; Conclusion: This study supports that SBRT to the spine results in high LC without any significant toxicity. The results of ongoing phase 3 trials will highlight whether this high LC benefit reflects to survival in oligometastatic disease.

Neoadjuvant Stereotactic Radiotherapy for Brain Metastases: Systematic Review and Meta-Analysis of the Literature and Ongoing Clinical Trials.

Simple SummaryThe available treatment strategies for patients with brain metastases remain suboptimal, with current research focused on identifying therapies intended to improve patient outcomes while reducing the risk of treatment-related complications. Several studies have investigated the role of pre-operative neoadjuvant stereotactic radiotherapy, and have proposed it as a valid alternative to post-operative adjuvant stereotactic radiotherapy. The aim of our systematic review was to comprehensively analyze the current literature and ongoing clinical trials evaluating neoadjuvant stereotactic radiotherapy in patients with brain metastases, describing treatment protocols and related outcomes. Early evidence suggests that neoadjuvant stereotactic radiotherapy may offer rates of local control and overall survival comparable to those obtained with adjuvant postoperative SRS, but comparative studies are currently lacking. In addition, neoadjuvant stereotactic radiotherapy shows low rates of post-treatment radiation necrosis and leptomeningeal metastases. Ongoing clinical trials aim to evaluate long-term outcomes in large patient cohorts, with some focused on comparing neoadjuvant stereotactic radiotherapy to adjuvant stereotactic radiosurgery.Background: Brain metastases (BMs) carry a high morbidity and mortality burden. Neoadjuvant stereotactic radiotherapy (NaSRT) has shown promising results. We systematically reviewed the literature on NaSRT for BMs. Methods: PubMed, EMBASE, Scopus, Web-of-Science, Cochrane, and ClinicalTrial.gov were searched following the PRISMA guidelines to include studies and ongoing trials reporting NaSRT for BMs. Indications, protocols, and outcomes were analyzed using indirect random-effect meta-analyses. Results: We included 7 studies comprising 460 patients with 483 BMs, and 13 ongoing trials. Most BMs originated from non-small lung cell carcinoma (41.4%), breast cancer (18.7%) and melanoma (43.6%). Most patients had single-BM (69.8%) located supratentorial (77.8%). Patients were eligible if they had histologically-proven primary tumors and ≤4 synchronous BMs candidate for non-urgent surgery and radiation. Patients with primary tumors clinically responsive to radiotherapy, prior brain radiation, and leptomeningeal metastases were deemed non-eligible. Median planning target volume was 9.9 cm3 (range, 2.9–57.1), and NaSRT was delivered in 1-fraction (90.9%), 5-fraction (4.8%), or 3-fraction (4.3%), with a median biological effective dose of 39.6 Gy10 (range, 35.7–60). Most patients received piecemeal (76.3%) and gross-total (94%) resection after a median of 1-day (range, 1–10) post-NaSRT. Median follow-up was 19.2-months (range, 1–41.3). Actuarial post-treatment rates were 4% (95%CI: 2–6%) for symptomatic radiation necrosis, 15% (95%CI: 12–18%) and 47% (95%CI: 42–52%) for local and distant recurrences, 6% (95%CI: 3–8%) for leptomeningeal metastases, 81% (95%CI: 75–87%) and 59% (95%CI: 54–63%) for 1-year local tumor control and overall survival. Conclusion: NaSRT is effective and safe for BMs. Ongoing trials will provide high-level evidence on long-term post-treatment outcomes, further compared to adjuvant stereotactic radiotherapy.

Comparative Metastatic Rates in GEP Class 1A versus 1B Posterior Uveal Melanoma: Results Contrary to Expectations

Purpose: The purpose of this study was to determine whether the metastatic rates in patients with gene expression profile (GEP) class 1A versus 1B posterior uveal malignant melanoma supported or contradicted predictions of very low metastatic rate in GEP 1A cases and moderate rate in GEP 1B cases. Patients/Methods: 164 patients with a cytopathologically confirmed primary posterior uveal malignant melanoma classified by GEP testing as class 1 (100 GEP 1A, 64 GEP 1B) were evaluated. Kaplan-Meier rates of metastasis were computed and plotted for the GEP class 1 subgroups. Median follow-up of patients who were still alive without metastasis on the date of data analysis was 100.5 months for the GEP 1A patients and 97.2 months for the GEP 1B patients. Results: The actuarial 5-year rate of uveal melanoma metastasis was 10.8% (std. error = 3.2%) in the GEP 1A patients versus 0% in the GEP 1B patients, and the actuarial 10-year rate of metastasis was 12.2% (std. error = 3.5%) in the GEP 1A patients versus 2.1% (std. error 2.1%) in the GEP 1B patients. Conclusion: The results of this retrospective single-center study cast doubt on the validity of the prognostic stratification of GEP class 1 posterior uveal malignant melanomas into very low risk (GEP 1A) versus intermediate risk (GEP 1B) of metastasis subgroups provided by the commercially available GEP test.

Clinical outcome of combined intracavitary / interstitial brachytherapy using a hybrid applicator in locally advanced cervical cancer

ObjectiveThe aim of this study was to evaluate the clinical outcome in locally advanced cervical cancer (LACC) after image-guided adaptive brachytherapy (IGABT) with combined intracavitary and interstitial (IC/IS) techniques using the hybrid Venezia applicator (Elekta AB, Sweden). MethodsLACC patients (UICC Stage IIB – IVB) treated with radiochemotherapy followed by IGABT with the hybrid IC/IS Venezia applicator at a single institution were retrospectively analyzed. Treatment comprised EBRT of the pelvis with 45 Gy and concomitant weekly cisplatin chemotherapy (40 mg/m2) followed by MRI-based IGABT. Dosimetry, oncological outcome and toxicity were investigated. ResultsForty-six patients underwent a total of 184 fractions of IGABT between 2017 and 2020. Median follow-up was 24 months. Combined IC/IS techniques were used in 40 patients (87%). The median HRCTV volume was 31.2 cm3 and the median HRCTV D90% was 92.3 Gy (EQD210). The median D2cm3 was 74.8 Gy for bladder, 57.9 Gy for rectum, 60.0 Gy for sigmoid and 52.2 Gy for bowel (EQD23). The 3-yr actuarial rates were 97.6% for local control, 97.6% for pelvic control, 59.9% for distant metastasis-free survival and 81.6% for overall survival. The crude rate for G2 and G3 late toxicity was 21.7% and 4.3%. ConclusionsIGABT with the hybrid Venezia applicator and a pronounced use of a combined IC/IS technique achieved high target doses, while maintaining low doses to organs at risk, leading to excellent local control and overall survival rates with acceptable toxicity.

Feasibility of accelerated image-guided high-dose-rate interstitial brachytherapy with inverse planning simulated annealing (IPSA-HDRBT) for post-operative treatment of pathologically node-negative squamous cell carcinomas of the oral tongue

Inverse planning simulated annealing (IPSA) produces highly conformal dose distributions and quick optimizations for high-dose-rate interstitial brachytherapy (HDRBT). We report our dosimetry and overall outcomes using this approach for the accelerated post-operative treatment of pathologically node-negative squamous cell carcinomas of the oral tongue (OTSCC) with high risk of local recurrence. Patients with newly diagnosed pN0 OTSCC treated with partial glossectomy, neck dissection, and post-operative HDRBT alone from 2007 to 2021 were retrospectively reviewed. Patients received 30 Gy in 5 fractions over 2.5 days. Target volume and mandible dosimetry are reported. Actuarial rates of local control, regional control, disease-specific survival, and overall survival were estimated using the Kaplan-Meier method. Toxicity was categorized using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. 19 consecutive patients were reviewed. Median follow-up was 3.2 years (IQR 1.4-8.2 years) with a 3-year estimated local control rate of 81%. Target volumes were generally small, as the median volume was 12.66 cc. Median V150% and V200% were 52% and 24%, respectively. D1cc and D2cc to the mandible were 17.31 Gy and 14.42 Gy, respectively. IPSA-HDRBT is feasible and highly efficient for post-operative treatment of the primary tumor bed in patients with pathologically node-negative squamous cell carcinomas of the oral tongue. Further technical optimization and prospective clinical evaluation in a larger patient cohort are planned.

Actuarial Patency Rates of Hepatico-Jejunal Anastomosis after Repair of Bile Duct Injury at a Reference Center.

Background: Bile duct injury complicates patients’ lives, despite the subsequent repair. Repairing the injury must restore continuity of the bile tree and bring the patient into a state of cure referred to as “patency”. Actuarial primary or actuarial secondary patency rates, depending on whether the patient underwent primary or secondary repair of injury, are proposed to be a proper metric in evaluating outcomes. This study was undertaken to assess outcomes of 669 patients with bile duct injuries Strasberg D and E type referred to the department from public surgical wards between 1990 and 2020. In 442 patients, no attempt was made to repair prior to a referral, and in 227 an attempt to repair was made which failed. Methods: Observations were summarized on December 31st, 2020. The retrospective analysis included: primary patency attained (Grade A result), secondary patency attained (Grade C result), patency loss, and actuarial patency rates of the bile tree at 2, 5, and 10 years. Results: Twenty-five (3.7%) patients died after repair surgery. Actuarial patency rates at 2, 5, and 10 years of follow-up were 93%, 88%, and 74% or 86%, 75%, and 55% in patients attaining Grade A and Grade C outcomes, respectively (p < 0.001). Conclusion: Bile duct injury stands out as a surgical challenge, requiring specialized management at a referral center. Improper proceeding after an injury is the factor leading to faster loss of anastomotic patency.

Plasma Circulating Tumor Epstein-Barr Virus for the Surveillance of Cancer Progression in Bone-Only Metastatic Nasopharyngeal Carcinoma.

BackgroundPlasma Epstein–Barr virus DNA (EBV-DNA) is a sensitive and specific biomarker for nasopharyngeal carcinoma (NPC). We investigated whether longitudinal monitoring of EBV-DNA could accurately detect clinical disease progression in NPC patients with bone-only metastases.MethodsIn this retrospective study, a total of 105 patients with bone-only metastatic NPC who were treated with platinum-based first-line chemotherapy were enrolled. Undetectable EBV-DNA after first-line chemotherapy was defined as a biochemical complete response (BCR). The correlation of the EBV-DNA dynamic status with overall survival (OS) and progression-free survival (PFS) was determined by Cox regression. The correlation between non-normalized EBV-DNA period and PFS period was determined.ResultsAfter a median follow-up time of 53.4 months [Interquartile range (IQR): 42.8–80.6], 64 patients had disease progression. Thirty-nine of 105 patients (37.1%) had a BCR at all follow-up time points, and none of these 39 patients had disease progression, corresponding to a negative predictive value (NPV) of 100%. Sixty-six patients had a detectable EBV-DNA during surveillance, with 64 diagnosed as disease progression at the last follow-up, for a positive predictive value (PPV) of 97.0%. Actuarial 3-year OS rates were 45.0% for patients with detectable EBV-DNA during posttreatment surveillance and 100% for patients with undetectable EBV-DNA. Lastly, median lead time between non-normalized EBV-DNA and clinically proven progression was 5.87 ± 0.67 months.ConclusionsTaken together, EBV-DNA provided predictive value for the bone-only metastatic NPC patients. The results should be validated in prospective randomized studies.

The Selective Personalized Radio-immunotherapy for Locally Advanced NSCLC Trial (SPRINT): Initial results.

8510 Background: Standard therapy for unresectable locally advanced non-small cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy followed by adjuvant durvalumab. We performed a prospective trial testing sequential pembrolizumab and risk-adapted radiotherapy without chemotherapy for biomarker-selected LA-NSCLC patients. Methods: Patients with stage III NSCLC or unresectable stage II NSCLC, ECOG performance status 0-1, and no contraindications to protocol-specified therapy were eligible for this trial. Subjects with PD-L1 tumor proportion score (TPS) ≥ 50% underwent baseline FDG-PET/CT, received three cycles of induction pembrolizumab (200 mg, every 21 days), underwent restaging FDG-PET/CT, received risk-adapted thoracic radiotherapy (55 Gy delivered to tumors or lymph nodes with metabolic tumor volume exceeding 20 cc and 48 Gy delivered to smaller lesions, all in 20 daily fractions), and then received up to 13 cycles of additional pembrolizumab. The primary study endpoint was one-year progression-free survival (PFS). Here we report response rates following induction pembrolizumab, PFS and overall survival (OS) rates, and adverse event rates (CTCAE v. 4.03). Results: Twenty-five subjects with PD-L1 TPS ≥ 50% from three institutions were enrolled between August 2018 and November 2021. Median age was 71 (interquartile range [IQR] 62 to 77). One subject had stage II disease, 13 had stage IIIA disease, nine had stage IIIB disease, and two had stage IIIC disease. Median PD-L1 TPS was 75% (IQR 60 to 80%). Two subjects (8%) developed disease progression during induction pembrolizumab, and two subjects discontinued pembrolizumab after one infusion due to immune-related adverse events. Using RECIST 1.1 criteria, 12 subjects (48%) exhibited a partial (n = 11) or complete (n = 1) response following induction pembrolizumab on CT. Using PERCIST criteria, 12 subjects (48%) exhibited a partial response following induction pembrolizumab on PET. Four subjects had responses on PET but not on CT, and four had responses on CT but not on PET. With a median follow-up duration of 13 months, the actuarial 1-year PFS rate is 74%, and the actuarial 1-year OS rate is 95%. Grade 3 adverse events have been limited to single cases of anemia, arthritis, diarrhea, esophagitis, and pneumonitis, and no grade 4-5 adverse events have occurred. Exploratory analyses suggest that response to induction pembrolizumab on PET predicts efficacy of this treatment approach, with a 1-year PFS rate of 100% for responders, compared to 61% for non-responders (logrank p = 0.007). Conclusions: Treatment with pembrolizumab and risk-adapted radiotherapy is a promising treatment approach for LA-NSCLC patients with PD-L1 TPS ≥ 50%. Response on PET following induction pembrolizumab may be useful for identifying patients who can be treated successfully without chemotherapy. Clinical trial information: NCT03523702.

Prognostic factors in sinonasal cancers: A multicenter pooled analysis.

6092 Background: Sinonasal cancers (SC) are heterogeneous diseases. Despite multimodality treatment, overall survival (OS) remains unsatisfactory. We aimed to identify prognostic factors (PFs) associated with patterns of failure and OS in non-metastatic SC (nmSC). Methods: We retrospectively reviewed a pooled dataset of nmSC from Princess Margaret (Canada) and Catalan Institute of Oncology (Spain) treated with definitive surgery ± postop radiotherapy (RT) or RT ± chemo according to institutional protocols between 2010-2019. In squamous cell carcinoma (SCC), HPV status was tested by p16 staining, and HPV DNA (ISH or PCR) if equivocal. The primary goal was to assess the association of tumor histology, stage (by 7th edition TNM), and other clinicopathological variables on locoregional control (LRC), distant control (DC) and OS. Actuarial rates were calculated with Kaplan–Meier (KM) method. Multivariable analysis (MVA) calculated hazard ratios (aHR) adjusted for histology type, T-/N-categories, and primary treatment. Results: Out of 342 pts, median age was 62 years (y) (range 21-96), Male:Female = 212:130, 95% had ECOG 0-1. Tumor histology types were: 192 (56%) SCC (p16+: 35; p16-/untested: 157), 40 (12%) adenocarcinoma (AD), 33 (10%) sinonasal undifferentiated carcinoma or sinonasal neuroendocrine tumors (SNUC/SNEC), 28 (8%) malignant melanoma (MM), 27 (8%) esthesioneuroblastoma (ES) and 22 (6%) adenoid cystic carcinoma (ACC). Median follow up was 3.6 y (range 0.1-11.3). Three-year actuarial rates for each endpoint are included in table. The PFs for LRC by MVA were: SNUC/SNEC (vs SCC) histology, T3-4 (vs T1-2: aHR 2.4, p = &lt; 0.01) and N+ (vs N-: aHR 1.7, p = 0.02) diseases. The PFs for DC were: MM (vs SCC) and SNUC/SNEC (vs SCC) histology, and T3-4 (vs T1-2: aHR 6.0, p = 0.01) disease. The PFs for OS were: MM (vs SCC) histology, older age (aHR 1.0, p &lt; 0.01), T3-4 (vs T1-2: aHR 5.6, p &lt; 0.01), and N+ (vs N-: aHR 2.5, p &lt; 0.01) disease. There was no difference in primary surgery vs RT in any outcome endpoint (all p &gt; 0.05). p16+ SCC had a marginally higher LRC but similar DC and OS vs p16-/untested SCC (table). Conclusions: This large multicentre cohort of nmSC shows different patterns of relapse and survival with different tumor histologies. Our results suggest that individualization of treatment and follow-up strategies by histologic type is recommended to optimize outcomes in these orphan diseases. [Table: see text]

Long-Term Survival in Patients With Papillary Thyroid Cancer Who Did Not Undergo Prophylactic Central Lymph Node Dissection: A SEER-Based Study.

BackgroundThe role of prophylactic central lymph node dissection (pCLND) for papillary thyroid cancer (PTC) remains contentious, and the impact of pCLND on long-term patient outcomes is unclear.MethodsA retrospective analysis of data from the Surveillance, Epidemiology, and End Results (SEER) database was performed. Patients diagnosed with PTC who did not undergo pCLND between 2004 and 2015 were included in this study, and patients with pN0 PTC who underwent CLND were included as the control group. The researchers calculated the subdistribution hazard ratio (SHR) using the Fine-Gray model and the hazard ratio (HR) using the Cox proportional hazards regression to compare Thyroid cancer-specific survival (TCSS) and overall survival (OS) of the different groups.ResultsA total of 38,205 T1-2cN0 PTC patients without pCLND were eligible for the study entry, and 24,157 patients with T1-2pN0 PTC patients who had received CLND were included as the control group. The actuarial 10-year TCSS and OS rates of patients without pCLND were 99.53% and 92.77%, respectively. Patients without pCLND had similar TCSS compared with the control group after adjusting for age, sex, race, tumor stage, multifocality, thyroid surgery, and radiation (SHR = 1.35, 95% CI: 0.95 - 1.93). However, patients without pCLND had a significantly poorer OS than the control group (HR = 1.38, 95% CI: 1.26 - 1.51).ConclusionsPatients without pCLND had similar TCSS compared with the control group after adjusting for confounders but had significantly poorer OS. Whether the OS disparities were attributed to pCLND or other factors still needs further study.

P.126 Cyberknife radiosurgery for trigeminal neuralgia: a retrospective review of 168 cases

Background: Gamma Knife radiosurgery for the treatment of refractory trigeminal neuralgia is recognized as an efficient intervention. The CyberKnife, a more recent frameless radiosurgery alternative, has not been studied as extensively for this condition. The aim of this study is to evaluate the clinical outcomes of a first CyberKnife radiosurgery treatment on patients with medically refractory trigeminal neuralgia. Methods: A retrospective study of 166 patients (168 cases) with refractory trigeminal neuralgia treated since 2009 with CyberKnife radiosurgery at the Centre Hospitalier de l’Université de Montreal (CHUM). Results: Adequate pain relief (Barrow Neurological Institute (BNI) pain scores I-IIIb) was achieved in 146 cases (86.9%). The median latency period before adequate pain relief was 35 days (range 0-202 days). The median duration of adequate pain relief was 15.8 months (range 0.6-85.0[DR1] [AG2] [AG3] [AG4] months). The actuarial rates of maintenance of adequate pain relief at 12, 36, and 60 months were 77.0%, 62.5%, and 50.2%, respectively. There was a new-onset or aggravation of facial numbness in 44 cases (26.2%). The maintenance of an adequate pain relief was more sustained in idiopathic cases in comparison to cases associated with multiple sclerosis (P&lt; 0.001). Conclusions: In our experience CyberKnife radiosurgery for refractory trigeminal neuralgia is efficacious and safe.

Comparison of toxicities between ultrahypofractionated radiotherapy versus brachytherapy with or without external beam radiotherapy for clinically localized prostate cancer

To compare gastrointestinal (GI) and genitourinary (GU) toxicities in patients with localized prostate cancer treated with ultrahypofractionated radiotherapy (UHF) or brachytherapy [BT; low dose rate, LDR or high dose rate (HDR) with or without external beam radiotherapy (EBRT)]. We compared 253 UHF and 1664 BT ± EBRT groups. The main outcomes were the incidence and severity of acute and late GU and GI toxicities. The secondary endpoint was biochemical control rate. Cumulative late actuarial GU toxicity did not differ for grade ≥ 2 (8.6% at 5-years in UHF and 13.3% in BT ± EBRT, hazard ratio [HR], 0.7066; 95% CI, 0.4093–1.22, p = 0.2127). Actuarial grade ≥ 2 late GI toxicity was higher in UHF (5.8% at 5-years, HR: 3.619; 95% CI, 1.774–7.383, p < 0.001) than in BT ± EBRT (1.1%). In detailed subgroup analyses, the high-dose UHF group (H-UHF) using BED ≥ 226 Gy1.5, showed higher GI toxicity profiles than the other subgroups (HDR + EBRT, LDR + EBRT, and LDR monotherapy, and L-UHF BED < 226 Gy1.5) with equivalent GU toxicity to other modalities. With a median follow-up period of 32 months and 75 months, the actuarial biochemical control rates were equivalent between the UHF and BT ± EBRT groups. UHF showed equivalent efficacy, higher GI and equivalent GU accumulated toxicity to BT ± EBRT, and the toxicity of UHF was largely dependent on the UHF schedule.

Adjuvant I-131 therapy for T0-3 N1b M0 differentiated thyroid cancer with many (≥ 5) positive nodes.

BackgroundIn patients with well-differentiated thyroid cancer, there is controversy about the prognostic importance of a large number of positive neck nodes and the potential value of radioiodine therapy. The purpose of this study was to evaluate this issue in the group of patients for whom it is most clinically important — those with classic histology and favorable T and M stage.Materials and methodsTwenty-five patients met the following inclusion criteria: classic histology of papillary or follicular thyroid carcinoma treated with total thyroidectomy and neck dissection followed by adjuvant I-131 treatment in our department between January 1, 2003, and December 31, 2013; adult age of > 21 years; and American Joint Committee on Cancer (AJCC ) stage (8th edition) of T0–3, N1b with ≥ 5 positive nodes, and M0.ResultsThe median positive node number was 10 (range, 5–31). The median adjuvant I-131 dose was 158 mCi (range, 150–219 mCi). The median follow-up in patients without recurrence after treatment was 7.3 years. The 10-year actuarial rates were favorable: overall survival, 100%; freedom from visible recurrence, 82%; and visible or biochemical recurrence, 72%.ConclusionRecurrence was infrequent in our study population with ≥ 5 positive nodes following moderate-dose adjuvant I-131 treatment. These results are valuable in directing initial adjuvant therapy and follow-up intensity. Our results do not inform the question of the use of postoperative thyroglobulin (Tg) level to select N1b patients for low-dose I-131 treatment.

Stereotactic body radiotherapy in oligometastatic cervical cancer (MITO-RT2/RAD study): a collaboration of MITO, AIRO GYN, and MaNGO groups

ObjectiveThis retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiotherapy in a large cohort of patients with oligometastatic/persistent/recurrent cervical cancer.MethodsA standardized data collection from several radiotherapy centers...

Postchemoradiotherapy Neutrophil-to-Lymphocyte Ratio Predicts Distant Metastasis and Survival Results in Locally Advanced Pancreatic Cancers.

Materials and Methods Our retrospective research included a sum of 126 LAPAC patients who received CCRT. The NLR was calculated for each patient based on the complete blood count test results obtained on the last day of the CCRT. The availability of optimal cutoff(s) that might dichotomize the whole cohort into two groups with significantly different clinical outcomes was searched using receiver operating characteristic (ROC) curve analysis. Primary and secondary endpoints were the potential association between the post-CCRT NLR measures and distant metastasis-free survival (DMFS) and overall survival (OS) outcomes. Results The median follow-up duration was 14.7 months (range: 2.4–94.5). The median and 3-year OS and DMFS rates for the whole group were 15.3 months (95% confidence interval: 12.4–18.2) and 14.5%, and 8.7 months (95% CI: 6.7–10.7) and 6.3% separately. The ROC curve analysis findings separated the patients into two groups on a rounded NLR cutoff of 3.1 (area under the curve (AUC): 75.4%; sensitivity: 74.2%; specificity: 73.9%) for OS and DMFS: NLR <3.1 (N = 62) and NLR ≥3.1 (N = 64), respectively. Comparisons between the NLR groups displayed that the median OS (11.4 vs. 21.4 months; P < 0.001) and DMFS (6.0 vs. 16.0 months; P < 0.001) lengths were significantly shorter in the NLR ≥3.1 group than its NLR <3.1 counterparts, as well as the 3-year actuarial DM rate (79.7% vs. 50.0%; P=0.003). The N1-2 nodal stage, CA 19–9>90 U/mL, and NLR >3.1 were found to be independent predictors of poor prognosis in the multivariate analysis. Conclusion The present study found that the posttreatment NLR ≥3.1 was independently linked with a higher risk of DM and subsequent degraded survival outcomes in unresectable LAPAC patients managed with exclusive CCRT.

Modified transventricular and transaortic mitral valve edge-to-edge repair mimicking MitraClip overcorrection.

ObjectiveIn the current study, we present our mid-term experience with modified edge-to-edge repair technique through a transventricular and transaortic route in patients requiring left ventricular remodeling or aortic root/valve surgery.MethodsFrom December 2006 through April 2015, 49 high-risk patients (median age: 69 years; median European System for Cardiac Operative Risk Evaluation II: 11.4 [6.54-14.9]) underwent transventricular (N = 7; 14%) or transaortic (N = 42; 86%) edge-to-edge mitral valve repair. The Alfieri stitch technique was modified by MitraClip type overcorrection and solid buttressing behind the posterior leaflet. Indication was grade 2+ functional mitral valve incompetence and dilated or impaired left ventricle (N = 25; 52%), or grade 3+ (N = 22; 45%) and grade 4+ functional mitral valve regurgitation (N = 2; 4%). Surgical procedure included aortic root surgery in 65%, aortic valve replacement with surgical revascularization in 18%, and Dor-plasty with surgical revascularization in 14%.ResultsIntraoperative mortality and early neurologic complications were absent in our series. Ninety-day mortality was 12.2% (N = 6). Median clinical and echocardiographic follow-up-time was 50.7 (21.5-44.1) and 39.2 (33.7-44.1) months, respectively. Median postoperative transvalvular gradient was low (2.72 [1.91-4.22] mm Hg) and did not increase during follow-up (P = .268), although peak gradient rose slightly from 7.41 to 8.12 mm Hg (P = .071). The actuarial reoperation free rate at the index valve was 96.8%.ConclusionsTransventricular or transaortic Alfieri mitral repair mimicking mitral clip overcorrection represents a quick and safe technique in the setting of high-risk patients undergoing left ventricular remodeling or aortic root/valve surgery and can be performed with low risk of creating mitral stenosis at midterm. The technique is straightforward, with reliable identification of the center of the valve leaflets being the limitation.

MAC: A Proposal for Consistent Actuarial Interest Rates in Pension Funds

ABSTRACT Objective: this article proposes the meta atuarial consistente (MAC) (consistent actuarial rate), which is a method that adjusts incompatible actuarial rates in pension funds, after investigating and proving that the rate dissociates from the general rule in current regulations (which binds this rate to the expected return of the investments of pension funds). Methodology: a sample with data from 22 defined-benefit plans was collected, and MAC was applied to produce consistent actuarial rates, after panel data methods have identified the elements that influence the definition of the actuarial rate by the pension fund board of trustees. Results: the use of MAC, adjusting actuarial rates of 2018 based on systematic biases in previous rates, enabled a positive effect that unfolds in more reliable estimates for the plans’ mathematical provision, while identifying elements that influence the determination of the annual rate, causing its non-compliance to the general rule. Conclusion: the adoption of MAC by the Brazilian supervisory authority Previc would improve the rules and provide subsidies to better adjust the contribution levels practiced in the plans, making their solvency levels more reliable, which would benefit the development of the insurance and pension market.