Actuarial Overall Survival Research Articles

Real-world data on utilization of neoadjuvant chemotherapy for muscle invasive bladder cancer: impact on surgical complications and oncological efficacy.

Recommended treatment of urothelial muscle-invasive bladder cancer (MIBC) is cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy, but there are challenges with low utilization of NAC. We aimed to evaluate the utilization of NAC, perioperative complications and oncological efficacy in a real-world setting. All patients operated with radical cystectomy at the University Hospital of North Norway during 2011-2021 for MIBC were included. NAC consisted of three cycles of dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (ddMVAC) every second week. Complications after cystectomy (Clavien-Dindo ≥ grade 3 within 30 days), histopathologic NAC response, cancer recurrence, relapse-free survival (RFS), overall survival (OS) and cause of death were reported. We included 124 patients, median observation time of 4 years. Fifty-nine patients (48%) received NAC. Most common causes for not receiving NAC were age ≥ 75 years (n = 38; 31%), cardiovascular disease (n = 7; 5.6%), and reduced kidney function (n = 6; 4.8%). Overall 34 patients (27%) had a ≥ grade 3 complication. The 5-year actuarial OS rate was higher among patients treated with NAC than those without NAC (67% vs. 45%, p = 0.02). Among NAC-treated patients, 29 (49%) were downstaged to non-muscle invasive stage (≤pT1), and the 5-year actuarial RFS and OS were higher among patients with ≤pT1 in the post-cystectomy specimen than those with ≥ pT2 (92% vs. 35%, and 94% vs. 39%, both p < 0.001). The utilization of NAC was high in this real-world setting. Treatment with ddMVAC with achieved downstaging to ≤pT1 was associated with considerably improved RFS and OS.

Elevated Serum IL-6 as a Negative Prognostic Biomarker in Glioblastoma: Integrating Bioinformatics and Clinical Validation.

Background: Glioblastoma multiforme (GBM) is the most lethal type of primary brain tumor, necessitating the discovery of reliable serum prognostic biomarkers. This study aimed to investigate the prognostic value of serum Interleukin-6 (IL-6) in GBM patients. Methods: Bioinformatics analysis via gene set enrichment analysis was conducted on The Cancer Genome Atlas RNA-seq data to explore the pathways enriched in samples with high IL-6 expression. The Tumor IMmune Estimation Resource database was used to analyze the association between IL-6 expression and immune cell infiltration. To validate the role of IL-6 in a clinical setting, a retrospective cohort study was conducted on newly diagnosed GBM patients. Serum IL-6 levels were repeatedly measured at key milestone time points, and their correlation with survival data was analyzed. Results: Bioinformatics analysis revealed that high IL-6 expression is associated with the activation of procancer pathways, that there is a positive correlation between IL-6 expression and immune cell infiltration in GBM. Between March 2021 and September 2023, 36 GBM patients and their serum IL-6 measurements at various time points were included in the clinical data analyses. Elevated serum IL-6 levels at baseline, with a cutoff of 7pg/mL, were identified in 11 patients (30.6%). In the multivariate analyses for overall survival (OS), elevated IL-6 was a significant risk factor (p = 0.048), along with unfavorable surgical resection (p = 0.039) and O6-methylguanine-DNA methyltransferase promotor unmethylation (p = 0.027). The median actuarial OS of the high initial IL-6 group was significantly shorter than that of the low initial IL-6 group (6.4 vs. 19.7 months, p < 0.001). However, IL-6 levels at other time points were not related to patient prognosis. Conclusion: Elevated IL-6 mRNA expression is correlated with the activation of procancer pathways, increased immune cell infiltration, and poor prognosis in GBM patients. In addition, elevated serum IL-6 at baseline is a negative prognostic factor confirmed in a clinical study. Serum IL-6 may be a potential prognostic biomarker enhancing the management of GBM.

Multi-institutional study using sbrt to treat mediastinal and hilar lymphadenopathy.

Mediastinal and hilar lymphadenopathy (MHL) is a common pattern of cancer spread, particularly in lung disease. Recently, there has been interest in the use of SBRT for MHL, especially in the oligometastatic setting. The goal is to improve local control (LC) and to achieve shorter treatment durations to minimize systemic treatment interruptions. The primary endpoint of this study was local control (LC). The secondary endpoints were distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) and predictive factors of response. This is a retrospective study. It analyses a group of patients treated with SBRT for MHL with different primary tumours and histologies. From November 2007 to June 2023, we treated 159 MHL in 128 patients. The primary most represented was lung cancer. A single fraction was used in 16% of cases and multiple fractions in 84% of cases. The medium BED 10 was 75.06Gy (range: 37-120Gy). Actuarial LC rates at 1, 2 and 5 years were 80.0%, 78.8% and 75.2%. The actuarial DMFS rates at 1, 2 and 5 years were 43.9%, 34.1% and 14.1%, respectively. Actuarial PFS rates at 1, 2 and 5 years were 37.2%, 23.9% and 8.3%, respectively. Actuarial OS rates at 1, 2 and 5 years were 68.8%, 52.7% and 26.9%, respectively. SBRT may be an option for the treatment of MHL. In addition, achieving a complete response is one of the most important predictors of our endpoints, in addition to tumour burden and volume.

Stereotactic Body Radiation Therapy for Oligoprogressive Ovarian Cancer Patients Treated During Poly(ADP‐Ribose)‐Polymerase Inhibitor Maintenance: Efficacy and Adverse Events From the Epimetheo Retrospective Study

The aim of this observational, retrospective, multicenter study (Epimetheo) was to analyze the activity and the safety of stereotactic body radiation therapy (SBRT) during poly(ADP-ribose)-polymerase inhibitor (PARPi) maintenance in a series of oligometastatic ovarian cancer (OC) patients. Patients treated with PARPi in maintenance setting received SBRT if oligometastatic progression occurred. Maintenance treatment was continued until the extensive progression of the disease. The primary endpoints of the study were as follows: next systemic treatment change-free survival (NEST-FS) and acute and late toxicity; the secondary endpoints were as follows: the rate of clinical complete response (CR), the 2-year actuarial local control (LC, progression of disease inside SBRT field) rate on "per lesion" basis, the 2-year actuarial progression-free survival, and 2-year overall survival (OS). From April 2018 to September 2023, SBRT was used to treat 74 OC patients with a total of 158 lesions (98 lymph nodes and 60 parenchymal lesions) under PARPi maintenance. Olaparib, niraparib, and rucaparib were administered to 41.9%, 48.6%, and 9.5% of patients, respectively. CR, partial response, stable disease, and progressive disease were observed in 115 (72.8%), 32 (20.3%), 9 (5.7%), and 2 lesions (1.3%), respectively. Severe toxicities were reported in less than 3% of patients. The actuarial median NEST-FS was 10 months, with a range of 6.7-13.3 months. The 12- and 24-month actuarial NEST-FS rates were 44.9% and 31.4%, respectively. The 2-year actuarial LC, progression-free survival, and OS were 68.1%, 22.5%, and 77%, respectively with differences in figures between complete and incomplete responders. The achievement of CR was found to be correlated with an improvement in LC and OS. This study reports the activity and the low toxicity profile of SBRT in association with PARPi in oligometastatic OC patients. A rapid, minimally invasive, and cost-effective treatment such as SBRT may be proposed as a means of prolonging NEST-FS and maintaining an effective treatment regimen involving PARPi.

Treatment Outcomes and Toxicity Profiles with PORTEC-3 Trial Regimen in South Asian Cohort of High-Risk Endometrial Cancer Patients: A Single-Center Ambispective Analysis

Objectives Adjuvant chemoradiation followed by chemotherapy is the current standard of care in high-risk endometrial cancer after the PORTEC-3 trial. There is a lack of data on this treatment regimen in the South Asian patient cohort. The present study aims to assess toxicity profiles and outcomes in this cohort of patients. Materials and Methods High-risk endometrial cancer patients planned for adjuvant chemoradiation followed by chemotherapy were included. Toxicity was graded using the Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events criteria. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Survival curves were compared using the log-rank test. Cox regression analysis was done to find out the predictors of DFS. Results This study included 58 patients treated from October 2016 to August 2022. Median age was 61 years (interquartile range [IQR] 56–66), with Fédération Internationale de Gynécologie et d'Obstétrique Stages I = 26 (44.8%), II = 5 (8.6%), and III = 27 (46.6%). p53 positivity was seen in 38 (65.5%) patients. Intensity-modulated radiotherapy was used in 44 (79.3%) patients. There was no treatment discontinuation during chemoradiation. Acute Grade 2 and above toxicity during chemoradiation were diarrhea in 10 (17.2%) and hematological in 2 (3.4%). For the planned adjuvant chemotherapy in 55 patients, 51 (92.7%) completed four cycles. Grade 2 or above neuropathy was seen in 11 (20%), with 5 (9%) having persisting neuropathy at 1-year follow-up. At a median follow-up of 31 months, 15 (25.8%) patients recurred; distant = 13 and isolated para-aortic = 2. The median time to recurrence was 16 months (IQR 12–22), with 80% (12 out of 15) of recurrence within the first 2 years of follow-up. The actuarial 5-year DFS and OS were 63.8 and 76.5%, respectively. In univariate analysis, p53 positivity and lymphovascular space invasion were predictors for DFS, with p-values 0.031 and 0.027, respectively. There was no significant predictor identified in multivariate analysis. Conclusion There is good tolerance and compliance to adjuvant chemoradiation and chemotherapy in this South Asian cohort of patients with high-risk endometrial cancer, with no toxicity-related treatment breaks during radiation. The majority of the recurrences were seen at distant sites and within the first 2 years of follow-up. These findings are in line with the outcomes of the PORTEC-3 trial.

Stereotactic radiotherapy for liver oligometastases: a pooled analysis following the estro/eortc consensus recommendations.

A large pooled analysis of liver oligometastases, classified accordingly to the ESTRO/EORTC recommendations, treated by stereotactic radiotherapy (SBRT) and Radiosurgery (SRS) was carried out. The clinical and dosimetric data of patients who underwent SBRT/SRS for liver metastases were analysed in terms of efficacy and toxicity profile. In particular, the Local Control (LC), the Distant Metastases Free Survival (DMFS), the Disease-Free Survival (DFS), the Overall Survival (OS), and the Next Systemic Therapy Free Survival (NEST-FS) rates were analysed. 113 patients (M/F: 49/64), accounting for a total of 150 hepatic lesions (March 2006-February 2023) in two Italian radiotherapy Institutions were evaluated. Median age was 67years old (36-92) and 48 (42.5%) patients had at least one comorbidity. The majority of the lesions were induced (30.7%) or repeated oligoprogressive (12.7%) metastases. 98 lesions were treated with more than one daily fraction (mainly 50Gy in 5 fractions), while 52 were radiosurgery treatments (mainly 32Gy). The treatment response at 3-4months was evaluable in 147 lesions: complete response was 32.0%, partial response 17.0%, and stable disease 32.0%. Actuarial LC, DMFS, DFS, OS, and NEST-FS at 1 year were 75.8%, 37.7%, 34.9%, 78.7%, and 59.4% respectively; while actuarial LC, DMFS, DFS, OS, and NEST-FS at 2 years were 52.1%, 24.9%, 21.9%, 51.3%, and 36.8%, respectively. The achievement of complete response, synchronous oligometastases, and no treatment interruptions correlated with a more favorable outcomes. As per the toxicity profile, we registered only two acute and one late toxicity cases higher than grade 2. Stereotactic treatment for liver metastases seems to be a safe and promising option in terms of local control. The best results in term of outcomes have been obtained in patients with complete response, synchronous oligometastases, favorable histology, and no treatment interruptions.

Relapse Hodgkin lymphoma autologous stem cell transplant long term follow up.

e19031 Background: Autologous Stem Cell Transplantation (ABMT) is a standard treatment approach for patients with relapsed Hodgkin’s Lymphoma (HL). We wish to report long term (&gt;10 year) outcomes for patient’s with HL treated with ABMT at our institution. Methods: We treated 35 patients over a 30 year time period (1992-2022). Of these 35 patients, there were 19 males and 16 females with a median age of 41 years (range 21-70 years) and a median performance status of 1 (0-1). The preparative regimen was carmustine, etoposide, and melphalam (CEM, 1992-2005) and BCNU, etoposide, cytarabine and melphalan (BEAM, 2006 to present). Bretuximab was added to BEAM in 2018 as post-transplant consolidation therapy in 13 patients. All patients underwent mobilized peripheral blood stem collections with high dose filgrastim, and starting in 2008 were mobilized with both filgrastim and plexiform. The required stem cell product was at a minimum of 2 million CD34+ cells per kilogram of body weight. Results: Fifteen patients received CEEM and 9/15 (60%) achieved a complete response (CR). Twenty patients received BEAM and 16/20 (80%) achieved a CR, p=0.27 (Fisher’s exact test). The median time to hematological recovery was 12 days (range 8-21). Treatment related complications included: S. epidermis sepsis (3 patients), E. coli sepsis (3 patients), and esophageal perforation that lead to death in 1 patient. With a median follow up 13 years (range 1-23 years), the actual 10 year disease free survival (DFS) is 52% and overall survival (OS) is 64%. The actuarial DFS and OS at 15 years are 52% and 64% respectively. Six patients are in continuous CR for greater than 20 years. Long term complications at greater than 15 years include: cardiomyopathy (5 patients), breast cancer (1 patient), and liposarcoma (1 patient). Conclusions: Patients with relapsed HL can achieve long term curative outcomes when treated with ABMT with most frequent long term complication being cardiomyopathy.

Use of Different Anti-PD-1 Checkpoint Combination Strategies for First-Line Advanced NSCLC Treatment-The Experience of Ion Chiricuță Oncology Institute.

Different combination modalities between an anti-PD-1/PD-L1 agent and a platinum-based chemotherapy or another checkpoint inhibitor (with or without a short course or full course of a platinum doublet) proved superior to chemotherapy alone in multiple clinical trials, but these strategies were not directly compared. The aim of this study is to report the real-world data results with different immunotherapy combinations in a series of patients treated in consecutive cohorts at the Ion Chiricuță Oncology Institute. A total of 122 patients were successively enrolled in three cohorts: (1A) nivolumab + ipilimumab (18 patients), (1B) nivolumab + ipilimumab + short-course chemotherapy (33 patients), and (2) pembrolizumab plus full-course chemotherapy (71 patients). Endpoints included overall survival (OS), progression-free survival (PFS), objective response (ORR), and univariate and multivariate exploratory analysis of prognostic factors. Median follow-up in the consecutive cohorts 1A, 1B, and 2 was 83 versus 59 versus 14.2 months. Median OS and PFS for all patients were 22.2 and 11.5 months, respectively, and 2-year actuarial OS and PFS were 49% and 35%, respectively. For the nivolumab + ipilimumab (cohorts 1A and 1B) versus pembrolizumab combinations (cohort 2), median OS was 14 vs. 24.8 months (p = 0.18) and 2-year actuarial survival 42% vs. 53%; median PFS was 8.6 vs. 12.7 months (p = 0.41) and 2-year actuarial PFS 34% vs. 35%; response rates were 33.3% vs. 47.9% (p = 0.22). Older age, impaired PS (2 versus 0-1), corticotherapy in the first month of immunotherapy, and >3.81 neutrophils to lymphocytes ratio were independent unfavorable prognostic factors in the multivariate analysis of survival (limited to 2 years follow-up). The 5-year long-term survival was 30.5% and 18.8% for cohorts 1A and 1B, respectively (not enough follow-up for cohort 2). Efficacy results using different immunotherapy combination strategies were promising and not significantly different between protocols at 2 years. Real-world efficacy and long-term results in our series were in line with those reported in the corresponding registration trials.

Pretreatment Circulating HPV16 DNA Viral Load Predicts Risk of Distant Metastasis in Patients with HPV16-Positive Oropharyngeal Cancer.

There are definite reasons to implement molecular diagnostics based on the measurement of human papillomavirus (HPV) DNA in liquid biopsy into clinical practice. It is a quick, repeatable, and health-safe test for cancer biomarkers in the blood. In this study, we investigated whether the circulating tumor-related HPV16 (ctHPV16) viral load (VL) in patients with oropharyngeal squamous cell carcinoma (OPSCC) was important for determining the risk of locoregional recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS). This study included 91 patients with ctHPV16-positive OPSCC who had been treated with radical radiotherapy and chemotherapy. The VL was measured using quantitative PCR (qPCR) and a probe specific for HPV16. Based on 10 years of follow-up, the 2-, 3-, 5-, and 9-year LRFS, MFS, and OS were estimated. The 5-year actuarial LRFS, MFS, and OS rates of patients with ctHPV16-positive/OPSCC were 88%, 90%, and 81%, respectively. The VL was significantly higher in patients who subsequently developed distant metastases (DM) than in those who did not (VL 4.09 vs. 3.25; p = 0.009). In a Cox proportional hazards regression model for MFS, a higher ctHPV16 VL appeared to be a significant independent prognostic factor for the occurrence of DM (HR 2.22, p = 0.015). The ROC curve revealed a cutoff value of 3.556 for VL (p = 0.00001). A high VL before treatment indicates patients with a significant risk of DM, and should be used in OPSCC treatment stratification.

Oligometastatic sarcoma treated with Curative intent Ablative Radiotherapy (OSCAR): A multicenter study on behalf of AIRO (Italian association of Radiotherapy and clinical Oncology)

Background and purposeStereotactic Ablative Radiotherapy (SABR) is emerging as a valid alternative to surgery in the oligometastatic setting in soft tissue sarcomas (STS), although robust data are lacking. The aim of this study is to evaluate toxicity and efficacy of SABR in oligometastatic STS. Materials and methodsThis is a retrospective multicenter study including adult patients affected by stage IV STS, treated with SABR for a maximum of 5 cranial or extracranial metastases in up to 3 different organs. SABR was delivered with ablative purposes. Study endpoints were overall survival (OS), local control (LC), distant progression free survival (DPFS), time to polymetastatic progression (TTPP), time to new systemic therapy (TTNS) and toxicity. ResultsFrom 10 Italian RT centers, 138 patients (202 metastases) treated between 2010 and 2022 were enrolled in the study. Treatment was generally well tolerated, no acute or late toxicity ≥ G3 was recorded. Median follow up was 42.5 months. Median OS was 39.7 months. Actuarial OS at 1 and 2 years was 91.5 % and 72.7 %. Actuarial LC at 1 and 2 years was 94.8 % and 88.0 %. Median DPFS was 9.7 months. Actuarial DPFS at 1 and 2 years was 40.8 % and 19.4 %. ConclusionSABR is a safe and effective approach for the treatment of oligometastatic sarcoma. One out of 5 patients is free of progression at 2-years.

Long Term Disease Free Survival and Survival of Patients with Relapsed Hodgkin's Lymphoma Treated with Autologous Stem Cell Transplantation

CONCLUSION Autologous Stem Cell Transplantation (ABMT) is a standard treatment approach for patients with relapsed Hodgkin's Lymphoma (HL). We wish to report long term (&amp;gt;10 year) outcomes for patient's with HL treated with ABMT at our institution. We treated 35 patients over a 30 year time period (1992-2022) Of these 35 patients, there were 19 males and 16 females with a median age of 41 years (range 21-70 years) and a median performance status of 1 (0-1). The preparative regimen was carmustine, etoposide, and melphalan (CEM,1992-2005) and BCNU, etoposide, cytarabine, and melphalan (BEAM, 2006 to present). Brentuximab was added was added to BEAM in 2018 as post-transplant consolidation therapy in 13 patients. All patients underwent mobilized peripheral blood stem cell collections with high dose filgrastim and since 2008 filgrastim and plexiform. The required stem cell product was at a minimum 2 million CD34+ cells per kilogram of body weight. Fifteen patients received CEM and 9/15 (60%) achieved a complete response (CR). Twenty patients received BEAM and 16/20 (80%) achieved a CR, p=0.27 (Fisher's exact test). The median time to hematologic recovery was 12 days (range 8-21). Treatment related complications included: S. Epidermis sepsis (3 patients), E. coli sepsis (3 patients) and esophageal perforation that lead to death (1 patient). With a median follow up of 13 years (range 1-23 years).The actual 10 year disease free survival (DFS) is 52% and overall survival (OS) is 64%. The actuarial DFS and OS at 15 years are 52% and 64% respectively. Six patients are in continuous CR for greater than 20 years. Long term complications at greater than 15 years include: cardiomyopathy (5 patients), breast cancer (1 patient), liposarcoma (1patient). Patients with relapsed HL can achieve long term curative outcomes when treated with ABMT. The most frequent long term complication is cardiomyopathy.

Real-world assessment of treatment multiple myeloma patients on the example of one hematology center

Relevance. Despite significant improvements in therapeutic options, patients with multiple myeloma (MM) experience a series of remissions and relapses requiring further lines of therapy, which requires the prescription of new lines of therapy. Methods. We analyzed the types and outcomes of treatment, attrition rates (AR) — the proportion of patients who dropped out of program therapy, and refractoriness to different lines of therapy (LOT) in 447 patients with MM between 2010 and 2022. Resalts. The AR was 17% between LOT-1 and LOT-2, 15% between LOT-2 and LOT-3, and 25% between LOT-3 and LOT- 4. In multivariate regression analysis, only high MM risk significantly increased AR risk. Each new progression of MM increased the number of patients with refractory to bortezomib, lenalidomide, or daratumumab. After LOT-1, LOT-2, and LOT-6%, 26%, and 53% of patients were double-refractory, respectively, and 54% were triple-refractory. Bortezomib- or lenalidomide-refractory patients had a 2.6-fold lower chance of achieving a very good partial response or better (VGPR+). From LOT-1 to LOT-4, the overall response rate and VGPR+ decreased from 74% and 53% to 25% and 15%, respectively. Overall survival (OS) in the entire population was 7.6 years, with an actuarial 5-year OS of 67% and a 10-year OS of 44%. The median of progression-free survival (PFS) was 20 months on LOT-1, 19 months on LOT-2, and 7 months on LOT-3, and the actuarial 5-year PFS was 25%, 18%, and 10%, respectively. Conclusions: In this regard, we observe a continuing trend in the use of cisplatin-containing "rescue" chemotherapy regimens, especially in patients with an aggressive course, including extramedullary forms of MM. These patients could be candidates for bispecific antibody therapy and CAR T-cell therapy, but these options are not yet available in Russia.

High Risk Prognostic Factors Predictive of Outcome Following Stereotactic Body Radiation Therapy (SBRT) for Early-Stage Lung Cancer

High risk prognostic factors for outcomes following SBRT for early-stage lung cancer per SWOG/NRG 1914 include: tumor size > 2cm; moderately/poorly/undifferentiated histology; or high metabolic activity on PET/CT defined as SUV > 6.2. The purpose of this IRB approved retrospective study is to assess outcome for stage I lung cancer and to validate SWOG risk stratification in a single community-based radiation department. A total of 132 patients with 139 tumors treated with SBRT between 2014 and 2019 were stratified by SWOG risk group (high vs. low). To assess differences by risk group in estimated overall survival (OS) at the patient level, as well as Freedom from Local Failure (FFLF), Freedom from Regional Failure (FFRF) and Freedom from Distant Failure (FFDF) at the tumor level, Kaplan-Meier methodology and Cox proportional hazards (PH) modeling for correlated data were used. Statistical significance was concluded at the 0.05 level. Median follow-up for the entire group is 56 months. 77% of patients had high risk tumors. The median patient age was 75 years with 57% female. Patients with high-risk tumors were older (p = 0.023) compared to patients with low-risk tumors. At the tumor level, high risk tumors were more likely to have biopsies performed (91% vs 57% p = 0.002) and more likely to experience regional failure (28% vs 7% p = 0.005). High risk tumors were more likely to experience local failure (8% vs 0% p = NS) and distant failure (27% vs 14% p = NS). Median survival was 49 months for the whole group (46.0 months high risk, 65.1 months low risk). Actuarial OS at 5 years is 38% (35% high risk, 51% low risk). Actuarial FFLF at 5 years is 94% (93% high risk, 100% low risk). Actuarial FFRF at 5 years is 77% (72% high risk, 93% low risk). Actuarial FFDF at 5 years is 74% (70% high risk, 88% low risk). Cox PH models revealed no statistically significant differences in FFRF by risk group (p = 0.08). Excellent local control but higher regional and distant failure was demonstrated for high-risk lung tumors as defined by SWOG/NRG 1914. Clinically important decrement in outcomes were consistently noted for high-risk tumors in this sample which did not demonstrate statistical significance due to lack of events and statistical power. However, our data supports the prognostic importance of tumor size/grade and SUV for identifying patients at high risk. Further validation with larger sample sizes would contribute to our knowledge regarding risk stratification for early-stage lung cancer treated with SBRT.

Predictive Value of Dynamic Tumor Volume Changes in Stage III Non-Small Cell Lung Cancer Treated with Chemoradiation and Consolidative Immunotherapy

Concurrent chemoradiation (CRT) followed by Immunotherapy is standard of care in unresectable, locally advanced, non-small cell lung cancer (NSCLC). We hypothesize that on-treatment dynamic changes in tumor volume may predict oncologic outcome in Stage III NSCLC. Stage III NSCLC patients who were treated with definitive CRT of 60 Gy in 30 fractions over 6 weeks with concurrent platinum-based concurrent chemotherapy followed by consolidative immunotherapy were retrospectively reviewed. We manually delineated the gross tumor volumes (GTV) of patients on cone beam computed tomography (CBCT) acquired on day 1, 15, 29 and 43. GTV reduction was quantified as the percent difference in volume on each CBCT as compared to CBCT Day 1. Mid-treatment response (MTR) and End of treatment response (ETR) was defined at day 29 (at 40 Gy) and day 43 (at 60 Gy), respectively. Loco-regional control (LRC) and overall survival (OS) was evaluated by Kaplan-Meier analysis, with log-rank test for groups stratified as per treatment response. Multivariate Cox regression analysis was performed to identify additional prognostic factors. We evaluated 24 consecutively treated patients from 01/2016 to 08/2019, with a median follow-up of 30.5 months. Median age was 69 years (range 51-84). Adenocarcinoma histology was present in 58 % and squamous cell carcinoma in 42% patients. The tumor stage IIIA in 38% and Stage IIIB in 62% patients. All patients received definitive CRT with at least 2 cycles of immunotherapy (median 8 cycles). The median ETR at CBCT43 was 49.5% (range, 1%-84.7%). 1-year cumulative incidence of loco-regional failure (LRF) was 27% versus 10% in patients with ETR <49.5% as compared to patients with greater ETR (p = 0.31). The median MTR at CBCT29 was 32.7% (range, 1%-81%). 1-year cumulative incidence of LRF was 28% versus 9% in patients MTR <32.7% as compared to patients with higher response (p = 0.03). The 3-year actuarial LRC of all patients was 51% which was significantly better in higher MTR (70% vs 30%; p = 0.02, log-rank) as compared to lower MTR. The 3-year actuarial OS for all patients was 45% which was 54% in patients with higher MTR verses 37% in low responders (p = 0.09). On multivariate analysis, age and T-stage were significant factors associated with LRC. Histologic subtype showed no impact on our findings. Stage III NSCLC patients with approximately one-third (33%) reduction of GTV on mid-treatment CBCT during CRT have significantly improved LRC and a trend towards improved OS. This approach may justify early adaptive intensification of RT or application of additional therapies in patients with non-optimal response. Additional large prospective study of CBCT is needed to determine whether treatment can be tailored based on tumor response, to improve outcomes.

Simultaneous Integrated Boost for Dose Escalation in Node-Positive Cervical Cancer: 5-Year Experience in a Single Institution.

This study retrospectively evaluates clinical outcomes of dose escalation to involved nodes using volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) for node-positive locally advanced cervical cancer (LACC) at a single institution. Consecutive patients with node-positive LACC (FIGO2018 IIIC1-IVA) who received definitive chemoradiotherapy by VMAT 45 Gy in 25 fractions with SIB to 55-57.5 Gy, followed by magnetic resonance image-guided adaptive brachytherapy (IGABT) between 2018 and 2022 were identified. A standardized strategy regarding nodal boost delivery and elective para-aortic (PAO) irradiation was employed. Primary endpoints were involved nodal control (INC) and regional nodal control (RNC). Secondary endpoints were pelvic control (PC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), failure pattern, and radiotherapy-related toxicities. A total of 234 involved nodes (182 pelvic and 52 PAO) in 54 patients, with a median of 3 involved nodes per patient (range 1-16), were analyzed. After a median follow-up of 19.6 months, excellent INC was achieved, with four (2%) boost-volume failures occurring in three patients. The 2-year actuarial RNC, PC, LRC, DFS, and OS were 93%, 87%, 87%, 78%, and 85%, respectively. Adenocarcinoma histology was associated with worse RNC (p = 0.02) and OS (p = 0.04), whereas the primary tumor maximum standardized uptake value (SUVmax) was associated with worse PC (p = 0.04) and LRC (p = 0.046) on univariate analysis. The incidence of grade ≥3 acute and late radiotherapy-related toxicity were 2% and 4%, respectively. Treatment of node-positive LACC with VMAT with SIB allows safe and effective dose escalation. The 5-year local experience demonstrated excellent treatment outcomes without additional toxicity.

Volumetric extent of resection and survival for recurrent atypical meningioma.

In recurrent atypical meningioma, the survival impact of volumetric extent of resection (vEOR) and residual tumor volume (RTV) has not been previously studied. The authors performed a retrospective vEOR analysis of patients with recurrent World Health Organization grade II meningiomas treated with reresection from 2000 to 2019. The Kaplan-Meier method and multivariate Cox regression analysis were used to study progression-free survival (PFS) and overall survival (OS). Fifty-nine patients with a median follow-up duration of 95 (95% CI 42-148) months were included. The median (range) vEOR was 100% (32%-100%) and the mean ± SD was 90.7% ± 15.3%. Among patients who underwent gross-total resection (GTR) (n = 32 [54%]), Simpson grade I and II resections were achieved in 23 (72%) and 9 (28%) patients, respectively. Among patients who underwent subtotal resection (n = 27 [46%]), the median (range) RTV was 4.3 (0.3-40) cm3. The 1-, 2-, and 5-year actuarial PFS rates for the cohort were 76%, 56%, and 34%, respectively. The 1-, 2-, and 5-year actuarial OS rates for the cohort were 98%, 78%, and 60%, respectively. Variables reflecting EOR significantly impacted both PFS and OS in multivariate analysis: GTR (p < 0.01) was significantly associated with longer PFS, and lower Simpson grade (p = 0.04) was significantly associated with longer OS. Additional factors including RTV, Ki-67 index, and pretreatment and posttreatment history also impacted survival outcomes (p < 0.05). EOR and Simpson grade were independently associated with survival outcomes in patients with recurrent atypical meningioma. These findings support the practice of thorough reresection for maximal cytoreduction in appropriate surgical candidates.

Impact of Short-Course Palliative Radiation Therapy on Pancreatic Cancer-Related Pain: Prospective Phase 2 Nonrandomized PAINPANC Trial

Clinical evidence is limited regarding palliative radiation therapy for relieving pancreatic cancer-related pain. We prospectively investigated pain response after short-course palliative radiation therapy in patients with moderate-to-severe pancreatic cancer-related pain. In this prospective phase 2 single center nonrandomized trial, 30 patients with moderate-to-severe pain (5-10, on a 0-10 scale) of pancreatic cancer refractory to pain medication, were treated with a short-course palliative radiation therapy; 24 Gy in 3 weekly fractions (2015-2018). Primary endpoint was defined as a clinically relevant average decrease of ≥2 points in pain severity, compared with baseline, within 7 weeks after the start of treatment. Secondary endpoint was global quality of life (QoL), with a clinically relevant increase of 5 to 10 points (0-100 scale). Pain severity reduction and QoL were assessed 9 times using the Brief Pain Inventory and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C15-PAL, respectively. Both outcomes were analyzed using joint modeling. In addition, acute toxicity based on clinician reporting and overall survival (OS) were assessed. Overall, 29 of 30 patients (96.7%) received palliative radiation therapy. At baseline, the median oral morphine equivalent daily dose was 129.5 mg (range, 20.0-540.0 mg), which decreased to 75.0 mg (range, 15.0-360.0 mg) after radiation (P=.021). Pain decreased on average 3.15 points from baseline to 7 weeks (one-sided P=.045). Patients reported a clinically relevant mean pain severity reduction from 5.9 to 3.8 points (P=.011) during the first 3 weeks, which further decreased to 3.2 until week 11, ending at 3.4 (P=.006) in week 21 after the first radiation therapy fraction. Global QoL significantly improved from 50.5 to 60.8 during the follow-up period (P=.001). Grade 3 acute toxicity occurred in 3 patients and no grade 4 to 5 toxicity was observed. Median OS was 11.8 weeks, with a 13.3% 1-year actuarial OS rate. Short-course palliative radiation therapy for pancreatic cancer-related pain was associated with rapid, clinically relevant reduction in pain severity, and clinically relevant improvement in global QoL, with mostly mild toxicity.

Post-Surgical Prognosis of Patients with Pineoblastoma: A Systematic Review and Individual Patient Data Analysis with Trends over Time

Most of the literature on pineoblastoma consists of case reports and single-institution series. The goal of this systematic review and individual patient data (IPD) analysis was to summarize the existing literature, identify factors associated with overall survival (OS), and provide a contemporary update on prognosis for patients with pineoblastoma. Forty-four studies were identified with 298 patients having IPD. Kaplan–Meier analyses were used to report survival outcomes based on age, tumor metastases, extent of resection (EOR), adjuvant therapy, and publication year. Cox regression was performed to identify independent predictors of time to mortality. Multivariable recursive partitioning analysis was used to identify the most important subgroups associated with mortality. Patients were classified based on publication year before and after the last systematic review on this topic (pre-2012 and 2012 onwards) and compared using univariate and multivariable analyses. This study demonstrates that EOR less-than-gross total resection, metastatic presentation, adjuvant chemotherapy without radiation, and tumor presentation in children less than three years old are associated with poorer prognosis. Since 2012, the 5-year actuarial OS has improved from 32.8% to 56.1%, which remained significant even after accounting for EOR, age, and adjuvant therapy. Pineoblastoma remains a severe rare disease, but survival outcomes are improving.

Carbon-ion radiotherapy in the treatment of radiation-induced second primary malignancies

Treatment of radiation-induced second primary malignancy (RI-SPM) is challenging and usually associated with poor outcomes. For patients with unresectable or incompletely resected diseases, carbon-ion radiotherapy (CIRT) offers physical and biologic advantages over photon-based re-irradiation. We report the results of salvage CIRT in 15 patients with RI-SPM. Fifteen consecutive and non-selected patients with RI-SPM who underwent salvage CIRT at the Shanghai Proton and Heavy Ion Center between November 2015 and May 2019 were included in this retrospective study. CIRT doses were 57.5-69 Gy (RBE) [at 2.5-3.0 Gy (RBE)/daily fraction]. The actuarial 1-year overall survival (OS), locoregional progression-free survival (LPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) rates as well as acute/late toxicities were analyzed. Among the 15 patients included, 10 were soft tissue sarcomas, 2 were chondrosarcomas, 1 was osteosarcoma, 1 was squamous cell carcinoma and 1 was esthesioneuroblastoma. With a median follow-up of 13.0 (range, 2.73-29.63) months, the actuarial 1-year OS, LPFS, DMFS, and PFS rates were 69.3%, 53.0%, 92.9%, and 48.2%, respectively. No grade 2 and grade 3 acute adverse effect was observed. One patient experienced grade 4 hemorrhage which required embolization during CIRT, and lately died from hemorrhage (grade 5) at 3.4 months after the completion of CIRT. No other late adverse effects of ≥ grade 2 was observed. Salvage CIRT provided relatively safe and effective short-term outcome for patients with unresectable or in-completely resected RI-SPM, as compared to historical data on re-irradiation using the conventional photon beam technology. However, further improvement in both disease control and toxicity prevention is needed.

Outcomes and Toxicity Following Three or More Definitive Courses of Thoracic Radiation Therapy

<h3>Purpose/Objective(s)</h3> Lung cancer patients are living longer but remain at risk for developing new or recurrent disease. Salvage re-irradiation can be considered for definitive management, but balancing efficacy with associated toxicity poses difficulty with retreatment. <h3>Materials/Methods</h3> This retrospective study evaluates patients who underwent three or more courses of definitive RT for thoracic malignancies at our cancer center from 2012 through 2021. All patients underwent multidisciplinary evaluation and restaging prior to retreatment. Toxicity was scored via CTCAE v5.0, and outcomes were estimated via Kaplan-Meier. <h3>Results</h3> Fifty-nine patients underwent a total of 190 definitive courses (13 having received 4 courses) for new or recurrent thoracic malignancies (88% non-small cell lung cancer). Of these courses, 141 (74%) entailed SBRT for localized lesions (most commonly to 50-Gy in 4-fractions), while the remaining 49 (26%) consisted of conventional fractionation (most often delivered with concurrent chemotherapy), with 22 patients (37%) receiving SBRT for every course. Median follow-up time was 7-years and 20-months from initial diagnosis and last RT course, respectively. All patients maintained excellent performance status (ECOG 0-2 or KPS 70-90) from first to last treatment. Median age at initial diagnosis and at last course of thoracic RT was 68.5 and 71 years, respectively, corresponding to median interval from initial RT to last RT course of 4 years. Twenty-eight patients (47%) had history of pulmonary disease, while 19 (32%) had history of prior lobectomy. Following last thoracic RT, median overall survival (OS) and progression-free survival (PFS) were still 2.4 years (95% CI: 1-4) and 12-months (95% CI 7-18), respectively. Actuarial OS at 1-year and 2-years was 73% and 54%, corresponding to PFS of 50% and 27%. However, 47 patients (80%) ultimately had evidence of progression, including distant metastases among 20 (43%), isolated locoregional recurrences in 19 (40%), and both as first progression for 8 (17%). Following last RT, the incidence of Grade 3 toxicity was only 5% (pulmonary and esophageal), with no Grade 4-5 events. There were no cardiac, neurological, or vascular toxicities directly attributable to RT. <h3>Conclusion</h3> Re-RT often remains a safe and effective local control modality (despite prior treatment) and should be considered as a potential option when planning multidisciplinary salvage therapy. For isolated failures, multiple courses of thoracic RT (notably SBRT) can be delivered sequentially with minimal toxicity.