Excellent Local Control Research Articles

QUALITY OF LIFE IN PATIENTS WITH SKULL BASE CHORDOMA AND CHONDROSARCOMA TREATED WITH PENCIL BEAM SCANNING PROTON THERAPY

Abstract AIMS The objective of this study is to assess the health-related quality of life (HRQoL) of skull base chor- doma/chondrosarcoma patients treated with proton therapy (PT). METHOD Seventy seven adult patients with skull base chordoma/chondrosarcoma completed the EORTC-QLQ-C30 and the BN20 Questionnaires prior to PT, Clinical outcome and therapy related acute and late toxicities have been recorded in course of the follow-up. The data was collected, categorized and analyzed, comparing the posttreatment scores to each patient’s baseline. In order to assess the impact of the clinical outcome and toxicities on HRQoL, the scores were correlated to collected clinical outcomes. RESULTS Median follow-up was 51 months. 6-year overall survival and local failure free survival rates observed were 85.1% and 80.3%. One G3 brain radiation necrosis and one G4 optic nerve disorder were documented during FU. HRQL deteriorated after the completion of proton therapy and returned to baseline values one year thereafter. After the second and third year, we observed further decrease in HRQL. This development was unrelated to tumor relapse. However, comparing the whole cohort over time, global QoL did not change substantially over the course of follow-up. GTR was correlated to better QoL at all time points. Disease progression was correlated with overall worse QoL and higher neurological symptoms already before PT, and higher symptom burden one year thereafter. Males had better QoL before and one year after PT than females. CONCLUSION PT achieves an excellent local and distant control in patients with skull base chordoma/chondrosarcoma. The HRQoL in these patients decreases immediately after the treatment completion, returns to the baseline from one year thereafter, and tends to deteriorate again with longer FU. The observed changes in global HRQoL were however not substantial in the whole cohort over the course of follow-up.

Interstitial brachytherapy for periocular nonmelanoma skin cancers: Impact on organ and function preservation

PurposeTo study the local control, toxicity, organ and functional preservation and cosmetic outcomes after interstitial brachytherapy for periocular nonmelanoma skin cancers. Methods and MaterialsPatients with skin cancers of upper and lower eyelid, medial and lateral canthus and the infra-orbital region treated with high dose rate (HDR) interstitial brachytherapy (ISBT) using 192-Iridium (192Ir) between December 2010 and July 2022 were included and data collected from a prospectively maintained database. Local control, survival outcomes, acute and late RTOG toxicity, functional and cosmetic outcomes were analysed. ResultsSixteen patients were included. Nine patients had lower eyelid tumors, 5 patients had tumors in canthi and two patients had skin tumor in the infra-orbital region. The median dose for definitive ISBT was 49 Gy in 14 fractions. After a median follow up of 73 months, all patients treated with definitive and adjuvant ISBT were locally controlled. Three of the four patients who received salvage ISBT for post-surgical failure had local recurrences and all were effectively managed with salvage re-surgery. Of the two deaths, none were disease related. Organ and function preservation was achieved in 15 (93.7 %) and 13 (81.2 %), respectively, with one patient being lost to follow up. Excellent, good, fair and poor cosmesis was seen in 6 (40 %) patients, 6 (40 %) patients, 2 (14 %) patients and 1(6 %) patient, respectively. ConclusionHDR-ISBT was safe and effective for skin tumors around the eye and resulted in excellent local control and survival outcomes preserving organ and function in majority of patients with good-excellent cosmesis.

High dose rate brachytherapy for lip cancer with interstitial, surface, or a combination of interstitial and surface mold technique

High-dose-rate brachytherapy (HDR-BT) is now becoming more common than low-dose-rate and pulsed-dose-rate BT in the treatment of lip cancer. However, due to the limited history of HDR-BT, relatively few studies have been published. Two institutions (in Ukraine and the USA) reviewed their clinical outcomes of lip cancer patients treated with HDR-BT as monotherapy or in combination with external beam radiotherapy (EBRT). An interstitial (IS), surface custom mold (SC), or a combination of IS and SC (IS+SC) was used for treatments based on the depth of tumor invasion. Prescription doses were 24 Gy in 6 BID fractions when combined with 46-50 Gy of EBRT, 45-55 Gy in 9-10 BID fractions for IS and IS+SC monotherapy or 3 Gy × 16 daily fractions for SC monotherapy. A total of 33 cases of lip cancer were treated from 2015 to 2021. By using TNM staging classification, there were 14 stage I (42.4%), 15 stage II (45.5%), and 4 stage III (12.1%) lip cancers. Thirty-one patients (93.9%) had a complete response to the treatment. Only 2 patients (6.1%) displayed local recurrence. Grade 1, 2, and 3 acute toxicities were observed in 30.3%, 51.5%, and 18.2% of patients, respectively. Grade 1, 2, and 3 late toxicities were observed in 39.4%, 21.2%, and 0.0% of cases. Cosmetic results were excellent in 21.2%, good in 54.5%, fair in 18.2%, and poor in 6.1% of patients. HDR-BT is an effective and safe treatment for lip carcinomas with excellent local control, functional, and cosmetic outcomes and should be considered as a standard treatment.

Long-term outcomes of more than a decade treating patients with stereotactic body radiation therapy for hepatocellular carcinoma

Purpose/Objective(s)To evaluate if stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) has a durable effect on tumor control and can be delivered safely. Materials/MethodsPatients included in this retrospective study have been treated at our institution from January 2008 to December 2022. Eligibility criteria were diagnosis of HCC, BCLC stage 0-A-B, non-cirrhotic liver or liver with cirrhosis Child-Pugh class A, and a maximum of three lesions with a cumulative diameter of ≤ 6 cm. Patients with relapses after surgery, thermal ablation or TACE or patients awaiting transplant were also candidates for SBRT. SBRT was delivered in 6 fractions of 8 or 9 Gy. The primary endpoint was local (target) control (LC). Secondary endpoints were time to progression (TTP), overall survival (OS), response rate (RR) and toxicity. ResultsA total of 52 patients received SBRT at our institution and 51 were included in this study. One patient objected and was excluded. Median follow-up was 2.1 years for LC and 2.3 years for OS. Median tumor size was 26 mm. LC rates at 1, 2, and 5 years were 100 %, 95 % and 95 % respectively. Median TTP was 45.6 months. Median OS was 7.1 years. RR was 96 %. No patients in this study have experienced SBRT related CTC AE grade ≥ 3 toxicity. ConclusionSBRT resulted in excellent long-term local control rates and absence of severe toxicity in a group of HCC patients. The reported outcomes compare favorably with other local therapies. SBRT should be considered as one of the available local treatment options for HCC.

Pleomorphic Liposarcoma of the Extremity and Trunk: Multimodality Therapy for Some but Not All?

Pleomorphic liposarcoma (PLPS) is an ultra-rare malignancy distinct from well-differentiated/dedifferentiated and myxoid liposarcoma. In this study, we sought to (1) assess outcomes after surgery for primary, non-metastatic PLPS and (2) explore potential indications for multimodality therapy. Clinicopathologic data were retrospectively collected for patients treated from 2002 to 2019 at our sarcoma referral center. Descriptive data were summarized and Kaplan-Meier plots were constructed for overall survival (OS) and crude cumulative incidences (CCI) of disease-specific death (DSD), local recurrence (LR), and distant metastasis (DM). Univariable models were performed to assess the association of specific variables of interest on outcome. Forty-four pathology-verified PLPS cases were included in this study. Median tumor size was 8.5 cm; 75% were FNCLCC Grade 3. All patients underwent complete resection, including 15 patients (34%) who required re-excision to secure microscopic negative margins. Radiation therapy was given to 75% of patients, chemotherapy in 36%. At 5 years, OS was 75.3%; CCI of DSD, LR, and DM were 17.5%, 2.3%, and 32.5%. Larger tumor size was strongly associated with worse OS (p = 0.028) and DSD (p ≤ 0.001). A subgroup of patients (n = 10, 23%) with smaller, predominantly Grade 2 tumors underwent surgery alone without any LR or DM event at a median follow-up of 7.9 years. In PLPS, aggressive surgery and when appropriate, radiation therapy, results in excellent local control. Chemotherapy can be considered for larger tumors. Patients with smaller, Grade 2 tumors may be potentially cured with surgery alone.

Stereotactic Body Radiotherapy (SBRT) for the Treatment of Primary Localized Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Context: Surgery is the gold standard for the local treatment of primary renal cell carcinoma (RCC), but alternatives are emerging. We conducted a systematic review and meta-analysis to assess the results of prospective studies using definitive stereotactic body radiotherapy (SBRT) to treat primary localised RCC. Evidence acquisition: This review was prospectively registered in PROSPERO (CRD42023447274). We searched PubMed, Embase, Scopus, and Google Scholar for reports of prospective studies published since 2003, describing the outcomes of SBRT for localised RCC. Meta-analyses were performed for local control (LC), overall survival (OS), and rates of adverse events (AEs) using generalised linear mixed models (GLMMs). Outcomes were presented as rates with corresponding 95% confidence intervals (95% CIs). Risk-of-bias was assessed using the ROBINS-I tool. Evidence synthesis: Of the 2983 records, 13 prospective studies (n = 308) were included in the meta-analysis. The median diameter of the irradiated tumours ranged between 1.9 and 5.5 cm in individual studies. Grade ≥ 3 AEs were reported in 15 patients, and their estimated rate was 0.03 (95%CI: 0.01–0.11; n = 291). One- and two-year LC rates were 0.98 (95%CI: 0.95–0.99; n = 293) and 0.97 (95%CI: 0.93–0.99; n = 253), while one- and two-year OS rates were 0.95 (95%CI: 0.88–0.98; n = 294) and 0.86 (95%CI: 0.77–0.91; n = 224). There was no statistically significant heterogeneity, and the estimations were consistent after excluding studies at a high risk of bias in a sensitivity analysis. Major limitations include a relatively short follow-up, inhomogeneous reporting of renal function deterioration, and a lack of prospective comparative evidence. Conclusions: The short-term results suggest that SBRT is a valuable treatment method for selected inoperable patients (or those who refuse surgery) with localised RCC associated with low rates of high-grade AEs and excellent LC. However, until the long-term data from randomised controlled trials are available, surgical management remains a standard of care in operable patients.

Oncologic outcomes and rates of hepatotoxicity following stereotactic body radiotherapy for hepatocellular carcinoma

Aim: Hepatocellular carcinoma (HCC) localized to the liver has various treatment options, including external beam radiotherapy (EBRT). Despite many prospective and retrospective reports showing excellent local control (LC) and favorable toxicity, EBRT has not been widely adopted in the first-line setting and this may be due to a perceived lack of evidence. This study aims to share a decade of experience with Stereotactic Body Radiotherapy (SBRT) for HCC, leveraging a homogenous treatment technique. Methods: This retrospective study at a single institution included patients with HCC treated with SBRT, with a standardized treatment protocol. Freedom from local progression (FFLP), overall survival (OS), and rates of hepatotoxicity post-treatment using child-pugh (CP) and albumin-bilirubin (ALBI) scores were analyzed. A mixed-effects multivariable analysis (MVA) was also performed to assess various factors’ impact on outcomes. Results: A total of 138 lesions in 106 patients were treated between 2009 and 2020. FFLP was 91% at one year and 86% at three years. OS was 80% and 46% at 1 and 3 years, respectively. Baseline liver function was a significant predictor of FFLP and OS on MVA. CP scores and ALBI grades were stable 3 months after treatment in ≥ 70% of patients. Conclusion: SBRT provides excellent LC and low toxicity for HCC patients. While long-term survival remains challenging, treatment decisions should consider overall clinical status. Multidisciplinary review and forthcoming prospective trial results will further clarify radiotherapy’s role in HCC management.

Comparison of Metastasectomy and Stereotactic Body Radiation Therapy for Pulmonary Oligometastasis From Hepatocellular Carcinoma: A Propensity Score-Weighted Analysis

Although there is a growing role for local therapy in patients with hepatocellular carcinoma (HCC) and pulmonary oligometastasis, it remains unclear whether metastatectomy or stereotactic body radiation therapy (SBRT) is the more effective treatment for these patients. We aimed to compare the oncologic outcomes of metastasectomy and SBRT for HCC with pulmonary oligometastasis. We retrospectively analyzed 209 patients with HCC with 322 metastatic lung lesions who underwent either metastasectomy (150 patients with 241 lesions) or SBRT (59 patients with 81 lesions) between January 2008 and December 2018. Propensity score-based inverse probability of treatment weighting was used to minimize potential bias between the 2 groups. The median follow-up duration was 39.8 months (range, 2.3-166.9 months). The 2-year rate of freedom from local progression was 98.2% in the metastasectomy group and 97.0% in the SBRT group (P = .197). The 2-year rates of overt systemic progression-free survival (PFS) (51.0% vs 46.1%; P = .274), PFS (26.3% vs 9.1%; P = .074), and overall survival (OS, 74.0% vs 57.6%; P = .006) were higher in the metastasectomy group. After the probability of treatment weighting adjustment, the 2-year rates of overt systemic PFS (50.8% vs 52.7%; P = .396), PFS (23.0% vs 24.7%; P = .478), and OS (72.6% vs 83.0%, P = .428) were not significantly different between the 2 groups. In multivariate analysis, viable intrahepatic lesions and the number of prior liver-directed therapies were found to be significant prognostic factors for OS and PFS. The time interval between HCC diagnosis and the development of pulmonary metastases was also significantly associated with OS. Both metastasectomy and SBRT demonstrated excellent local control and comparable oncologic outcomes in patients with pulmonary oligometastasis from HCC. The treatment modality for these patients could be determined based on the individual patient's condition and intrahepatic disease status.

A phase 2 single-arm trial of high-dose precision targeted radiotherapy added to immunotherapy for patients with metastatic non-small cell lung cancer.

For metastatic non-small cell lung cancer (NSCLC), the addition of radiotherapy (RT) to immune checkpoint inhibitor (ICI) therapy could have synergistic anti-cancer effects and address the most threatening tumors. We posited that the addition of high-dose RT to ICI could prolong progression-free survival (PFS). In this single arm phase 2 trial, 45 patients with metastatic NSCLC who had received an anti-PD-1/anti-PD-L-1 ICI for 4+ weeks were enrolled from July 2017-May 2021. Patients received high-dose RT to 1-4 extracranial tumors and continued ICI until progression or unacceptable toxicity. The primary endpoint was PFS at 24 weeks, comparing to a historical control rate of 35%. Of 44 evaluable patients, median age was 71, 75% had adenocarcinoma, 64% had polymetastatic disease, and 85% of cancers with known PD-L1 percentage were PD-L1 positive. Median number of treated tumors was two and most common dose was 40 Gy in 10 fractions (41/81 tumors). Median follow-up was 23.3 months. The trial met the primary outcome: 24-week PFS was 60% (95% CI 44-75%), higher than the historical control rate (p<0.001). Median PFS was 6.9 months (95% CI 4.0-13.5 mo) and median OS was 27.4 months (95% CI 20.4-not reached). Several patients with pre-study disease progression on ICI treatment achieved durable responses to study treatment, up to 53 months. Local recurrence rate was low: cumulative incidence of 5% at one, two, and three years. Two dose-limiting toxicities were observed (5%), including one grade 5 pneumonitis. The strategy improved 24-week PFS compared to historical controls receiving ICI alone. The excellent local control supports the efficacy of high-dose RT in addressing macroscopic disease.

Stereotactic centralized ablative radiation therapy: A novel methodology in treating bulky tumor and its technical realization.

159 Background: Bulky tumors pose significant challenges to traditional treatment modalities such as surgery, chemotherapy, and conventional radiotherapy. This study introduces a novel therapeutic approach named as Stereotactic-Core-Ablative-Radiation-Therapy (SCART), designed to deliver an ablative dose to a substantial core of the bulky tumor while quickly decreasing to a lower dose at the tumor periphery. Methods: A SCART-Treatment-Volume (STV) at the core of the GTV was predefined to administer an ablative radiation dose, aiming to induce DNA damage in cancer cells and potentially trigger biological cancer-killing effects. Utilizing Linac-based VMAT or Cyberknife techniques with 6MV photon beams, multiple radiation fields intersect and optimize at STV, generating an ablative dose at the STV. The dose rapidly diminishes to a safe level at the edge of GTV sparing the surrounding tissue. In the phase-1 trial, nineteen patients with 21 bulky tumors enrolled, receiving SCART at five dose levels (15GyX1, 15GyX2, 15GyX3, 18GyX3, 21GyX3, and 24GyX3), while maintaining the GTV's peripheral dose at 5Gy each fraction. Results: All patients completed treatment with average beam-on time of 8.9min and average treatment time of 18.5min. Mean follow-up time is 15.4 month. No grade-III or higher toxicity was observed. 7/19 patients still survive, with the overall survival of 40% at 30 months. Mean tumor volume shrinks by 60% between initial 301cc and post-SCART volumes of 118cc. Long-term follow-up revealed that 14/21 tumors achieved Partial Response, 2/21 Complete-Response, 3/21 Stable-Disease, and 1/21 Progressive-Disease, leading to an encouraging local control of 95%. Conclusions: SCART emerges as a safe and effective strategy for treating bulky malignant tumors, demonstrating excellent local control and overall survival. Multiple treatment courses were feasible. The results from phase-1 study suggest that SCART could revolutionize the treatment landscape for bulky tumors, offering a promising avenue for further exploration and application in clinical practice.

Clinical Outcomes of Proton Beam Therapy for Unresectable Locally Advanced Pancreatic Cancer: A Single-Center Retrospective Study

PurposeWe retrospectively researched the treatment outcome of proton beam therapy (PBT) and assessed its efficacy for inoperable locally advanced pancreatic cancer (LAPC) at our institution. Materials and MethodsFifty-four patients (28 males and 26 females, median age 67 years of ranges from 40 to 88 years were diagnosed with unresectable stage III LAPC and administered PBT from April 2009 to March 2020. Either patients who could not complete PBT, or had new distant metastases during the treatment, or did not have enough follow-up time were excluded from this study. All patients were clinically staged based on the International Union of Cancer TNM staging system (UICC 8th edition) using CT, MRI, and PET, and were diagnosed as stage III (histologic type: eighteen adenocarcinoma patients, thirty-six clinically diagnosed patients). PBT was performed using the passive method, with a median total dose of 67.5 GyE (range: 50-77 GyE/25-35 fractions). Chemotherapy was used in combination during PBT in forty-six patients (85.2%). Overall survival (OS), local progression-free survival (LPFS), progression-free survival (PFS), and median overall survival time (MST) were analyzed by Kaplan-Meier and log-rank tests. Univariate and multivariate analyses were performed for the following factors: maximum standardized uptake value (SUVmax), ECOG-performance status (PS), tumor site, total irradiation dose, concurrent chemotherapy, and primary tumor site. Cutoff values for SUVmax and tumor diameter were estimated using receiver operating characteristic (ROC) curves and area under the curve (AUC) based on OS. Multivariate analysis was evaluated using the Cox proportional hazards models. Adverse events were evaluated using CTCAE ver. 5.0. ResultsThe median observation period was 17.4 months of ranges from 4.0 to 89.7 months. The median tumor diameter was 36.5 mm of ranges from 15 to 90 mm, the median SUVmax was 5.85 (range: 2.1-27.6), and their cutoff values were estimated to 37 mm and 4.8 mm, respectively. 1-, 2-year OS were 77.8%, 35.2% with MST 18.2 months, respectively and only one patient survived more than 5 years. 12 patients (22.2%) developed local recurrence, and 1-, 2-year LPFS rate were 89.7% and 74.5%, respectively; PFS at 1-year was 58.8%. PS score, Tumor site and irradiation dose were the prognostic factor related to OS that showed a significant difference. On the other hand, there was a significant difference in factors involved in LPFS, 96.7%/77.9% in the first year and 86.6%/54.4% in the second year in the groups with tumor dose ≥67.5 GyE and <67.5 GyE, respectively (p = 0.015). Treatment-related acute toxicities were neutropenia (Grade1/2/3:3.7%/11.1%/31.5%), leukopenia (Grade 1/2/3:1.8%/7.4%/20.4%), and thrombocytopenia (Grade 1/2:1.8%/7.4%), while the late effects including peptic ulcer were captured only grade2+. The late adverse events of Grade 3 or higher were not observed. ConclusionsPBT achieving 67.5 Gy combined with standard chemotherapy showed the excellent local control for unresectable LAPC. Total irradiation dose, Tumor site and PS score at an initial diagnosis could be important prognostic factors. In this study, the dose-effect relationship was found so an increase in dose should be considered to improve prognosis.

Intraoperative radiotherapy after neurosurgical resection of brain metastases as institutional standard treatment- update of the oncological outcome form a single center cohort after 117 procedures.

Stereotactic radiotherapy (SRT) is the predominant method for the irradiation of resection cavities after resection of brain metastases (BM). Intraoperative radiotherapy (IORT) with 50kV x-rays is an alternative way to irradiate the resection cavity focally. We have already reported the outcome of our first 40 IORT patients treated until 2020. Since then, IORT has become the predominant cavity treatment in our center due to patients´ choice. We retrospectively analyzed the outcomes of all patients who underwent resection of BM and IORT between 2013 and August 2023 at Augsburg University Medical Center (UKA). We identified 105 patients with 117 resected BM treated with 50kV x-ray IORT. Median diameter of the resected metastases was 3.1cm (range 1.3 - 7.0cm). Median applied dose was 20Gy. All patients received standardized follow-up (FU) including three-monthly MRI of the brain. Mean FU was 14months, with a median MRI FU for patients alive of nine months. Median overall survival (OS) of all treated patients was 18.2months (estimated 1-year OS 57.7%). The observed local control (LC) rate of the resection cavity was 90.5% (estimated 1-year LC 84.2%). Distant brain control (DC) was 61.9% (estimated 1-year DC 47.9%). Only 16.2% of all patients needed WBI in the further course of disease. The observed radio necrosis rate was 2.6%. After 117 procedures IORT still appears to be a safe and appealing way to perform cavity RT after neurosurgical resection of BM with low toxicity and excellent LC.

Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiotherapy in patients with locally advanced rectal cancer: long-term results of the UNICANCER-PRODIGE 23 trial

The standard of care for the treatment of locally advanced rectal cancer (LARC) results in an excellent local disease control but the metastasis rates remain high. PRODIGE 23 demonstrated improved disease-free survival (DFS) and metastasis-free survival (MFS) with total neoadjuvant therapy versus standard of care in this population. Long-term analysis of overall survival (OS) is reported here. The study design, participants, and primary endpoint DFS have been reported for this multicenter, randomized, open-label, phase III trial investigating the neoadjuvant chemotherapy with mFOLFIRINOX (6 cycles) followed by chemoradiotherapy, surgery, and adjuvant chemotherapy (6 cycles), versus chemoradiotherapy, surgery, and adjuvant chemotherapy (12 cycles) in patients with locally advanced rectal adenocarcinoma under peritoneal reflection on magnetic resonance imaging, and staged cT3/T4. Key secondary endpoints included OS, MFS, and local and metastatic recurrence rate. With a median follow-up of 82.2 months, the 7-year DFS was 67.6% [95% confidence interval (CI) 60.7% to 73.9%] and 62.5% (95% CI 55.6% to 68.6%) [restricted mean survival time (RMST) difference 5.73 months, 95% CI 0.05-11.41 months, P= 0.048] in the neoadjuvant chemotherapy and the standard-of-care groups, respectively. The 7-year MFS was 79.2% (95% CI 73.0% to 84.4%) in the neoadjuvant chemotherapy group and 72.3% (95% CI 65.8% to 77.8%) in the standard-of-care group (RMST difference 6.1 months, 95% CI 0.93-11.37 months, P= 0.021). The 7-year OS was 81.9% (95% CI 75.8% to 86.6%) in the neoadjuvant chemotherapy group and 76.1% (95% CI 69.7% to 81.2%) in the standard-of-care group (RMST difference 4.37 months, 95% CI 0.35-8.38 months, P= 0.033). The safety profile remained unchanged since the previous analysis. Neoadjuvant chemotherapy with mFOLFIRINOX followed by chemoradiotherapy improved OS, confirmed long-term DFS and MFS benefits in LARC patients, and should be considered as one of the best options of care for these patients.

Pattern of care and clinical outcome of patients with carcinoma endometrium and the impact of central histopathological review on management: A tertiary cancer centre experience.

Endometrial carcinoma (EC) is the third most common gynecological malignancy in India. Recent PORTEC-3 analysis emphasized the role of central histopathological review. We aimed to retrospectively analyze the demographic and histopathological characteristics of EC patients treated at our institute and assess the impact of the central histopathological review on management and also analyze clinical outcomes in this cohort of patients. Data of 75 EC patients treated at our center between 2013 and 2022 were retrieved from our departmental archives. Patients were analyzed for demographic details, histopathological findings, details of surgery and histopathology (HPE), results of a review of HPE, adjuvant treatment details, and clinical outcomes. All patients with HPE outside of our institute were reviewed at our center prior to initiation of treatment. In cases of discordance, patients were discussed in the multidisciplinary tumor board for the final treatment decisions. Patients were staged as per International Federation of Gynaecology and Obstetrics 2018. The median age was 57 years (range: 37-74 years). Twenty-seven patients with HPE reported from the outside center were reviewed at our institute and changes were observed in 26 patients (96.3%). HPE review changes were observed in terms of histological grade, histological type, myometrial invasion, and lymph node involvement in five (18.5%), three (11.1%), seven (25.9%), and three (42.8%), respectively. HPE review leads to changes in the management of 19/26 patients. Stage distribution was I: II: III in 48 (64%): 9 (13.3%): 18 (24%) patients, respectively. The median external beam radiotherapy dose was 50 Gray (range: 45-50.4 Gray at 1.8-2 Gray per fraction). The median brachytherapy dose for patients treated with brachytherapy alone was 7 Gray each for three sessions and in combination with EBRT was 6 Gray each in two sessions. At a median follow-up of 51 months (range: 6-116 months), seven (9.3%) patients developed distant metastasis, two (2.7%) patients had local plus distant metastasis, and two (2.7%) patients had local recurrence. The overall survival and disease-free survival rates at 3 years were 93.5% and 86.7%, respectively. EC patients treated at our center have excellent local control rates with a combination of external beam radiotherapy and brachytherapy. The central histopathological review may result in changes impacting patient management and should be routinely done prior to initiation of treatment in EC.

Phase II Trial Assessing Toxicity of Personalized Response-Based Radiation Treatment in Patients with Locally Advanced Non-Small Cell Lung Cancer

IntroductionLocal failure rates after treatment for locally advanced non-small-cell lung cancer (NSCLC) remain high. Efforts to improve local control with uniform dose-escalation or dose-escalation to mid-treatment PET-avid residual disease have been limited by heightened toxicity. This trial aimed to refine response-based adaptive radiation (RT) and minimize toxicity by incorporating FDG-PET and V/Q SPECT imaging mid-treatment. Methods47 patients with Stage IIA-III unresectable NSCLC were prospectively enrolled in this single-institution trial (NCT02492867). Patients received concurrent chemoradiation with personalized response-based adaptive RT over 30 fractions incorporating V/Q SPECT and FDG-PET. The first 21 fractions (46.2Gy at 2.2 Gy/fraction) were delivered to the tumor while minimizing dose to SPECT-defined functional lung. The plan was then adapted for the final 9 fractions (2.2-3.8Gy/fraction) up to a total of 80.4Gy, based on mid-treatment FDG-PET tumor response to escalate dose to residual tumor while minimizing dose to SPECT-defined functional lung. Non-progressing patients received consolidative carboplatin/paclitaxel or durvalumab. The primary endpoint of the study was ≥ grade 2 lung and esophageal toxicities. Secondary endpoints included time to local progression, tumor response, and overall survival. ResultsAt one year post-treatment, the rates of grade 2 and grade 3 pneumonitis were 21.3% and 2.1%, respectively, with no difference in pneumonitis rates among patients who received and did not receive adjuvant durvalumab (p=0.74). While there were no grade 3 esophageal-related toxicities, 66.0% of patients experienced grade 2 esophagitis. 1- and 2-year local control rates were 94.5% (95% CI, 87.4% - 100%) and 87.5% (95% CI, 76.7% - 100%), respectively. Overall survival was 82.8% (95% CI, 72.6% -94.4%) at 1 year and 62.3% (95% CI, 49.6%-78.3%) at 2 years. ConclusionsResponse-based adaptive dose-escalation accounting for tumor change and normal tissue function during treatment provided excellent local control, comparable toxicity to standard chemoradiation, and did not increase toxicity with adjuvant immunotherapy.

Theragnostic Gadolinium-Based Nanoparticles Safely Augment X-ray Radiation Effects in Patients with Cervical Cancer.

Activated guided irradiation by X-ray (AGuIX) nanoparticles are gadolinium-based agents that have the dual benefit of mimicking the effects of a magnetic resonance imaging (MRI) contrast agent used in a clinical routine and enhancing the radiotherapeutic activity of conventional X-rays (for cancer treatment). This "theragnostic" action is explained on the one hand by the paramagnetic properties of gadolinium and on the other hand by the generation of high densities of secondary radiation following the interaction of ionizing radiation and high-Z atoms, which leads to enhanced radiation dose deposits within the tumors where the nanoparticles accumulate. Here, we report the results of a phase I trial that aimed to assess the safety and determine the optimal dose of AGuIX nanoparticles in combination with chemoradiation and brachytherapy in patients with locally advanced cervical cancer. AGuIX nanoparticles were administered intravenously and appropriately accumulated within tumors on a dose-dependent manner, as assessed by T1-weighted MRI, with a rapid urinary clearance of uncaught nanoparticles. We show that the observed tumor accumulation of the compounds can support precise delineation of functional target volumes at the time of brachytherapy based on gadolinium enhancement. AGuIX nanoparticles combined with chemoradiation appeared well tolerated among the 12 patients treated, with no dose-limiting toxicity observed. Treatment yielded excellent local control, with all patients achieving complete remission of the primary tumor. One patient had a distant tumor recurrence. These results demonstrate the clinical feasibility of using theranostic nanoparticles to augment the accuracy of MRI-based treatments while focally enhancing the radiation activity in tumors.

Effectiveness of the Use of Denosumab When Performing Intralesional Surgery in Patients with Gigant Cell Tumors of the Bones of the Knee Joint

In intralesional resection of giant cell tumors, local recurrence rate can be as high as 60–65 %. Some authors attribute recurrences to the presence of an extraosseus component and pathologic fractures, others focus on the effectiveness of bone cavity processing. Currently, denosumab is widely used in treatment of giant cell tumors of the bone. Most frequently, it is used in neoadjuvant regimen at dose 120 mg. This regimen allows to decrease the volume of extraosseous tumor component, form bone margins, and, as a result, make radical resection easier. However, the number of publications on increased risk of local tumor recurrence after neoadjuvant denosumab administration has been growing.Aim. To evaluate the effectiveness of various denosumab administration regimens in intralesional tumor resection in patients with giant cell tumors of the bones forming the knee joint.Materials and methods. The prospective study included outcomes of integrated treatment of 65 patients (34 (52.3 %) women and 31 (47.7 %) men) who underwent surgery at the Division of Bone Oncology of the National Scientific Research Center for Traumatology and Orthopedics named after R.R. Vreden due to giant cell tumors of the knee joint between 2017 and 2023. Mean patient age was 37.5 ± 9.79 years (95 % confidence interval 35.11–39.96; range 19–61 years). Mean follow-up duration was 40.2 ± 13.3 months (95 % confidence interval 36.87–43.46; range 18–68 months). To perform comparative analysis, the patients were divided into 2 groups depending on treatment type. The Group 1 (control) included 32 patients who subcutaneously received 120 mg denosumab prior to surgery (4 injections once a week and then once a month; total number of injections was 6 or more) with subsequent intralesional tumor resection, defect reconstruction with cement in combination with external fixation using a lockable condylar plate. The Group 2 (treatment) included 33 patients who underwent the same surgery as patients of Group 1 and then received subcutaneous injections of 120 mg denosumab (1 injection once a month for 3 months after surgery). Classification and analysis of complications were performed using the International Society of Limb Salvage (ISOLS) 2014 system. Functional outcomes were evaluated using the Musculoskeletal Tumor Society Score (MSTS) at 3, 6, and 12 months.Results. Mean time of recurrence diagnosis in the Group 1 was 9.1 months, in the Group 2 – 14.3 months. Evaluation of the probability of local tumor recurrence depending on treatment type showed statistically significant differences (p = 0.001). Odds of local recurrence in the Group 2 were 10.6 times lower than in the Group 1, and odds of revision surgical intervention in this patient group was 14.5 times higher (with higher probability, this surgery involved oncological endoprosthesis) (p = 0.011). No statistically significant differences in development of distant metastases and probability of death depending on treatment type were found (p = 0.492). According to the obtained data, there are statistically significant differences in functioning of the knee joint per the MSTS scale in the Groups 1 and 2 at 6 and 12 months (p = 0.021 and p = 0.021, respectively). Functional outcomes were better in the Group 2. No significant differences in knee joint functioning per the MSTS scale at 3 months depending on treatment type were found (p = 0.764).Conclusion. Administration of denosumab in the postoperative period allows to improve oncological outcomes due to decreased number of local recurrences (2 (6.1 %) cases), maintenance of excellent local control and good functional results, and to decrease the probability of revision surgical intervention to a minimum. In our study, administration of this drug prior to surgery (intralesional tumor resection) significantly increased the risk of local tumor recurrence (p = 0.001).

Mohs Micrographic Surgery With Immunohistochemistry for the Treatment of Periocular Melanoma In Situ.

Mohs micrographic surgery with immunohistochemistry allows for same-day comprehensive margin assessment of melanoma in situ prior to subspecialty reconstruction. This study describes the oncologic and reconstructive outcomes of eyelid and periorbital melanoma in situ and identifies risk factors for complex reconstructive demands. Retrospective case series of all patients treated with Mohs micrographic surgery with immunohistochemistry for melanoma in situ affecting the eyelids or periorbital region from 2008 to 2018 at a single institution. Tumors were assigned to the eyelid group if the clinically visible tumor involved the skin inside the orbital rim. Reconstructive variables were compared between the eyelid and periorbital cohorts. There were 24 eyelid and 141 periorbital tumors included. The initial surgical margin for all tumors was 5.34 ± 1.54 mm and multiple Mohs stages were required in 24.2% of cases. Eyelid tumors included more recurrences (p = 0.003), and the average defect size was larger (14.0 ± 13.3 cm2 vs. 7.7 ± 5.4 cm2, p = 0.03). Risk factors for complex reconstruction included: initial tumor diameter >2 cm (odds ratio [OR]: 3.84, 95% confidence interval [CI]: 1.95-7.57) and eyelid involved by initial tumor (OR: 4.88, 95% CI: 1.94-12.28). At an average follow-up of 4.8 years, there were no melanoma-related deaths and 1 local recurrence (0.6% recurrence rate). Mohs micrographic surgery with immunohistochemistry achieves excellent local control rates for periocular melanoma in situ. An initial surgical margin of 5 mm is frequently insufficient to achieve clear margins. The resulting defects are large, and the complexity of reconstruction can be predicted by tumor size and clinical involvement of eyelid skin.

Overall survival following heterogeneous FDG-guided dose-escalation for locally advanced NSCLC in the international phase III NARLAL2 trial.

LBA8069 Background: The survival and loco-regional control for patients (pts) with locally advanced non-small cell lung cancer (LA_NSCLC) treated with radiotherapy (RT) are dismal despite adjuvant Durvalumab. However, there have been concerns about dose escalation for these pts since the unexpected result of the dose-escalation trial RTOG0617. A novel approach is therefore warranted to escalate the dose to the tumor. A possible approach is to use the principle from stereotactic body radiotherapy (SBRT) with inhomogeneous dose distribution. SBRT has demonstrated excellent local control in early-stage lung cancer. The international multicenter NARLAL2 (novel approach to RT for LA_NSCLC) phase III trial on dose escalation, randomized pts with LA_NSCLC between standard 66 Gy/ 33 fractions (F) versus heterogeneous FDG-PET driven dose escalation, aiming at mean dose to GTV-tumorPET 95 Gy/ 33 F and mean dose to GTV-nodePET 74 Gy/ 33 F while strictly respecting dose to organs at risk. We here present the data on overall survival (OS) 1 year after the end of recruitment. Methods: Pts aged ≥18 years with LA_NSCLC were recruited from seven institutions in Denmark and Norway. Eligibility criteria included ECOG PS 0-1, histological or cytological confirmed NSCLC stage IIB-IIIB, signed informed consent, and a clinically acceptable plan for RT with conventional 66 Gy/ 33 F. PET-CT and brain MR were part of staging. Pts were randomly assigned to either treatment group (1:1, stratified for center and histology). The trial aimed to have iso-lung toxicity within the treatment arms by creating two RT plans (before randomization) for each patient (one for each treatment arm) with matching mean lung dose and lung V20Gy. The follow-up (FU) were scheduled weekly during RT, every 3rd month for 2 years, and every 6th month for another 3 years after randomization. At FU visit a CT-scan and toxicity scoring were performed. All interim analyses were passed without interventions (toxicity and OS). The trial's primary endpoint was time to loco-regional failure from randomization. Secondary endpoints included OS, acute, and late toxicity. The sample size calculations requested 350 pts to be enrolled in the study. Recruitment of the pre-planned number of pts finalized in March 2023. The trial was registered with ClinicalTrials.gov (NCT02354274). Results: From January 2015 to March 2023, 350 pts were randomized: 177 and 173 pts in standard and escalated arms respectively. The two groups were well-balanced regarding age, gender, stage, and PS. The dose to GTV-tumor was 66.5 Gy [66.2, 67.1] (median [IQR]) in the standard arm and 88.1 Gy [84.9, 90.4] in the escalated arm. Median OS were 35.8 months (m) and 51.6 m for pts treated in the standard and escalated arm, respectively ( p = 0.36). Median FU time 50.8 m (reverse Kaplan-Meier). Conclusions: Dose escalation is safe in the NARLAL2 setting with respect to OS. Clinical trial information: NCT02354274 .

Hepatic artery infusion of FOLFOX chemotherapy and camrelizumab combined with sorafenib for advanced stage hepatocellular carcinoma (Double-IA-001): A phase II trial.

e16199 Background: Hepatic arterial infusion chemotherapy (HAIC) using a combination of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown excellent local control for hepatocellular carcinoma (HCC) patients classified under Barcelona Clinic Liver Cancer (BCLC) stage C. In China, both camrelizumab (a PD-1 inhibitor) and sorafenib were approved first-line approach for advanced stage HCC. This study (ChiCTR2100041874) aimed to the efficacy of combined hepatic artery infusion of FOLFOX chemotherapy and camrelizumab, together with sorafenib in BCLC stage C. Methods: Eligible patients were given a maximum of six cycles of hepatic artery infusion of HAIC-FOLFOX and camrelizumab, along with sorafenib, until either disease progression, intolerable toxicities emerged or disease downstaged and converted to received surgical resection. The primary outcome measured was the objective response rate (ORR) based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results: Twenty-five patients were enrolled. Based on mRECIST criteria, by the end of Feb 4, 2024, the confirmed ORR stood at 44.0%, with a disease control rate of 60.0%. The median progression-free survival was 3.33 months. Patient quality of life had a transient deterioration within four cycles of treatment, and generally recovered thereafter. A total of 28.0% of patients had grade ≥3 or above treatment-related adverse events, which could be alleviated after symptomatic treatment. Conclusions: The combination of double intrahepatic infusion of FOLFOX and camrelizumab with sorafenib demonstrated encouraging results and manageable safety concerns for BCLC stage C HCC. Clinical trial information: ChiCTR2100041874.