Previous Radiation Research Articles

Progressive Disease with Mixed Response After Immunotherapy in Non-Small Cell Lung Cancer.

There exists a dearth of research concerning non-small cell lung cancer (NSCLC) patients experiencing overall progressive disease concomitant with shrinking lesions after immunotherapy. This is a special type of mixed response. We aim to evaluate the clinical characteristics and treatment options of these patients during immunotherapy. We categorized patients into two groups: Progressive Disease with Mixed Responses (PDMR) (n = 31) and Progressive Disease with None Mixed Responses (PDNMR) (n = 144), depending on whether at least one target lesion had shrunk by ≥30% at the point of overall progression. Computed tomography scans and magnetic resonance imaging were utilized to evaluate the clinicopathological significance of these patients, and a multivariate analysis was conducted to scrutinize the clinical characteristics and prognosis-influencing factors in these patients. Patients in the PDMR group had worse staging and a greater proportion of previous radiotherapy. The median overall survival (mOS 22 vs 36.4 months; P = 0.019) and median progression-free survival (mPFS 5.83 vs 9.03 months; P = 0.031) of the PDMR group were shorter than PDNMR group. Longer subsequent OS with continued immunotherapy after PDMR compared with patients who do not continue with immunization after PDMR (mOS 23.9 vs 6.5 months; P = 0.024). PDMR was primarily observed in stage IV patients and previously irradiated patients. OS and PFS were inferior in patients with PDMR compared to patients with PDNMR. The continuation of immunotherapy in PDMR patients could extend their survival.

Distress Scores in Elderly Cancer Patients During Radiotherapy.

When assigned to radiotherapy (RT), elderly patients may experience distress. We investigated distress during RT and potential risk factors in these patients. Six-hundred-and-nineteen patients completed pre-RT and post-RT distress thermometers. Seven characteristics were investigated including age, sex, Karnofsky performance score (KPS), grouped KPS, tumor type, intent of RT, and previous RT. Additional analyses were performed in 358 patients with pre-RT scores ≤5. Mean change of distress was -0.5 (±2.7) points and associated with KPS (p=0.005) and grouped KPS (p<0.001). Male sex (p=0.035), KPS 90-100 (p=0.001), and curative intent (p=0.037) were associated with increased distress on univariable analyses, and KPS 90-100 (odds ratio=1.92, p=0.004) on multivariable analysis. In patients with baseline scores ≤5, mean change was +0.5 (±2.5) points and associated with KPS (p=0.040) and grouped KPS (p=0.025). Psychological assistance should be considered for all patients including those with baseline scores ≤5 and KPS 90-100. Patients with risk factors for increased distress would especially benefit.

Protocol of the HISTOTHERM study: assessing the response to hyperthermia and hypofractionated radiotherapy in recurrent breast cancer.

Breast cancer is globally the leading cancer in women, and despite the high 5-year survival rate the most frequent cause of cancer related deaths. Surgery, systemic therapy and radiotherapy are the three pillars of curative breast cancer treatment. However, locoregional recurrences frequently occur after initial treatment and are often challenging to treat, amongst others due to high doses of previous radiotherapy treatments. Radiotherapy can be combined with local hyperthermia to sensitize tumor cells to radiation and thereby significantly reduce the required radiation dose. Therefore, the combination treatment of mild local hyperthermia, i.e. locally heating of the tissue to 39-43°C, and re-irradiation with a reduced total dose is a relevant treatment option for previously irradiated patients. The mechanisms of this effect in the course of the therapy are to date not well understood and will be investigated in the HISTOTHERM study. Patients with local or (loco)regional recurrent breast cancer with macroscopic tumors are included in the study. Local tumor control is evaluated clinically and histologically during the course of a combination treatment of 60 minutes mild superficial hyperthermia (39 - 43°C) using water-filtered infrared A (wIRA) irradiation, immediately followed by hypofractionated re-irradiation with a total dose of 20-24 Gy, administered in weekly doses of 4 Gy. Tumor and tumor stroma biopsies as well as blood samples will be collected prior to treatment, during therapy (at a dose of 12 Gy) and in the follow-up to monitor therapy response. The treatment represents the standard operating procedure for hyperthermia plus re-irradiation. Various tissue and blood-based markers are analyzed. We aim at pinpointing key mechanisms and markers for therapy response which may help guiding treatment decisions in future. In addition, quality of life in the course of treatment will be assessed and survival data will be evaluated. The study is registered at the German Clinical Trials Register, Deutsches Register Klinischer Studien (DRKS00029221).

Predictors for quality of life, pain and functional outcomes after surgical treatment of metastatic disease in the spine

BackgroundWhile predictors for postoperative survival in spine tumour patients have been identified, there is limited evidence for predictors of postoperative Quality of Life (QoL), pain and functional outcome. MethodsOne hundred and fifty-three consecutive patients, who had undergone surgery for symptomatic spinal metastases between June 2016 and April 2019, were interviewed preoperatively and during follow-ups at three, six and 12 months using the EQ-5D-3L, COMI, and ODI questionnaires. Differences in means exceeding the specific Minimal Clinically Important Difference (MCID) values were considered clinically significant. ResultsThirty-three percent of the patients were reported dead after 12 months. Only one metastasis compared to multiple metastases has 7.9 the Odds for an improved EQ-5D-3L score at three months. No neoadjuvant metastatic irradiation has 6.8 the Odds for the improvement at that time against performed radiation. A preoperative ODI score between 50.1 and 100 has 22.0 times the odds compared to the range from 0 to 50 for an improved EQ-5D-3L after three months, and 12.5 times the odds in favour of improved COMI after three months, and 13.6 times the odds for improvement of ODI at the three-month follow-up. A preoperative COMI score ranging from 5.0 to 10 has 21 times the odds of a COMI between 0 and 5 for an improved EQ-5D-3L score and 11 times the odds for an improved ODI after 12 months. Other predictors showed no statistically significant improvement. ConclusionAn improvement in QoL, pain and spinal function after 12 months can be predicted by a subjective preoperative poor health condition. Impaired spinal function before surgery, a singular metastasis and no previous irradiation is predictive of improved spinal function and quality of life three months after surgery.

Peripheral blood stem cells mobilization in patients with relapsed or refractory lymphomas: A single-center experience.

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) is an established treatment for chemosensitive patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). We present the results of using different salvage chemotherapy plus granulocyte colony stimulating factor (G-CSF) for mobilization of peripheral blood stem cells in R/R lymphoma patients. For salvage chemotherapy, 93 patients received platinum-containing regimens, 4 patients received cytarabine-containing regimens, and 5 patients received other regimens. Patient distributions were HL (n = 35) and NHL (n = 67). In 87.2% of patients, first mobilization trial was successful (>2 × 10 6 CD34+ cells/kg). In 58.8% of patients, first apheresis season >5 × 10 6 CD34+ cells/kg collections was achieved. All 12.7% of patients were poorly mobilized at the first mobilization. There was no statistical difference between the previous chemotherapy numbers and failed mobilization ( P > 0.05). Five patients who were poorly mobilized and 4 patients who were successfully mobilized underwent a previous radiotherapy ( P < 0.05). Thirteen patients who were poorly mobilized in the first mobilization underwent a platinum-containing salvage regimen. At the time of the first mobilization, the average peripheral CD 34 counts in the successfully mobilized group were statistically higher than that in the poorly mobilized group ( P < 0.01). We demonstrated that peripheral CD 34 cell count in the peripheral blood on the first apheresis day was a significant factor for more stem cell mobilization, fewer apheresis sessions, less volume, and earlier neutrophil engraftment for patients with R/R lymphoma and eligible for AHSCT. The history of the previous radiotherapy was a significant factor for poor mobilization.

Central Neck Lymph Node Size Measured by Ultrasound Significantly Predicts Central Neck Lymph Node Metastasis of Papillary Thyroid Carcinoma.

Objective: The aim of this study was to investigate whether Central lymph node (CLN) size as measured by an ultrasound can significantly predict CLN metastasis of papillary thyroid carcinoma (PTC). Materials and methods: This retrospective chart review of patients diagnosed with PTC who underwent ultrasound and central neck dissection (CND). We excluded patients who received previous thyroid surgery or radiation. We analyzed the correlation between CLN size and characteristics by ultrasound and histopathologic findings among positive CLN patients. Results: Of the 48 patients who underwent preoperative ultrasound and CND, 34 patients had positive CLN identified by ultrasound. The positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of ultrasound in this diagnostic setting was 88.0%, 21.0%, 73.2%, 42.9%, and 68.7%, respectively. The risk of CLN metastasis of PTC was 67.7% and 85.7% for lymph node size 3.1 to 4 mm and 4.1 to 5 mm, respectively. The risk increased to 100% when the lymph node size was >5 mm. Positive preoperative ultrasound of lateral neck lymph node was found to be a significant risk factor for CLN metastasis (P = .003). Conclusion: Ultrasound was found to be an effective preoperative evaluation in patients with PTC to determine the likelihood of CLN metastasis and whether CND is indicated, especially in the ultrasound-positive central lymph node. A high risk of metastasis was found in CLN size >3 mm by ultrasound, and the risk dramatically increased in CLN size >5 mm. We also found positive lateral neck node from preoperative ultrasound to be a significant risk factor for CLN metastasis.

Previous external beam radiation therapy for pelvic malignancy increases complications of total hip arthroplasty.

External beam radiation therapy (EBRT) has known effects on bone health. No large database studies have looked at the effects of pelvic EBRT on total hip arthroplasty (THA) outcomes. The purpose of this study was to evaluate 90-day and long-term (>2 years) complication rates following THA in patients with a history of pelvic malignancy and EBRT. Patients were retrospectively identified using a national insurance claims database. Subjects who underwent THA for osteoarthritis or avascular necrosis were included if they had at least 2-year follow-up and were stratified into 3 cohorts: (1) prior pelvic malignancy diagnosis (prostate, cervical, uterine, ovarian, or rectal) and EBRT (Group A); (2) prior malignancy diagnosis but no EBRT (Group B); and (3) neither prior malignancy diagnosis nor EBRT (Group C). Univariate and multivariate analyses were conducted to evaluate for an association between prior EBRT and the incidence of 90-day and 2-year complication rates using chi-square, student t-tests, and logistic regression analyses where appropriate. 671,554 patients met the inclusion criteria. Group A had higher odds of all-cause revision, septic revision, and loosening with revision after 2 years when compared to Group C and Group B (p < 0.001). Group A subjects had higher rates of 90-day deep vein thrombosis, sepsis, and stroke (p < 0.001) than groups B and C. Prior EBRT for pelvic malignancy was associated with significantly increased rates of all-cause revision, septic revision, and loosening as well as 90-day medical complications.

A comparative dose-escalation analysis for reirradiated cancer patients with and without appropriate dose mapping.

This study aims to compare dose escalation between two groups of reirradiated cancer patients, one with the previous contour and radiotherapy plan available on the treatment planning system and the other without. First group is identified as DICOM-group, while the other one is called non-DICOM group. The current study included 89 patients, 57 in the DICOM, and 32 in the non-DICOM group, who received reirradiation for recurrent or second primary tumours between 2019 and 2021. For the DICOM group, doses to 0.2cc volume for spine, brainstem, and optic apparatus from first radiation were converted into structures and transferred to reirradiation CT using deformable registration. First, one radiotherapy plan was created using the doctor prescribed dose (baseline prescription RxD_B); further an escalated dose (RxD_E) plan, taking into account all the dose volume parameters from previous radiation, was created only for DICOM group. In non-DICOM group patients were planned only for RxD_B. The maximum accepted dose escalation was 21 Gy. Radiotherapy prescription dose during earlier (first) treatment in DICOM and non-DICOM groups were 61 ± 5.6 Gy and 30-66 Gy, respectively. DICOM and non-DICOM groups had nearly identical baseline doses: 52.5 ± 10.7 Gy and 50.6 ± 6.9 Gy (difference 1.9 ± 12.7 Gy). Dose escalation was possible for 51 out of 57 patients in the DICOM-group. Average escalated dose in DICOM-group was 59.2 ± 6.2 Gy, with an incremental dose of 6.7 ± 12.4 Gy from the baseline prescription. No dose escalation was opted for in the non-DICOM group due to the unavailability of dose volume information from previous radiation. Reirradiation for head and neck cases allowed for a moderate to high dose escalation, facilitated by the presence of pertinent DICOM information from the initial radiotherapy.

Proton Reirradiation for High-Risk Recurrent or New Primary Breast Cancer.

Radiotherapy is an integral component of multidisciplinary breast cancer care. Given how commonly radiotherapy is used in the treatment of breast cancer, many patients with recurrences have received previous radiotherapy. Patients with new primary breast cancer may also have received previous radiotherapy to the thoracic region. Curative doses and comprehensive field photon reirradiation (reRT) have often been avoided in these patients due to concerns for severe toxicities to organs-at-risk (OARs), such as the heart, lungs, brachial plexus, and soft tissue. However, many patients may benefit from definitive-intent reRT, such as patients with high-risk disease features such as lymph node involvement and dermal/epidermal invasion. Proton therapy is a potentially advantageous treatment option for delivery of reRT due to its lack of exit dose and greater conformality that allow for enhanced non-target tissue sparing of previously irradiated tissues. In this review, we discuss the clinical applications of proton therapy for patients with breast cancer requiring reRT, the currently available literature and how it compares to historical photon reRT outcomes, treatment planning considerations, and questions in this area warranting further study. Given the dosimetric advantages of protons and the data reported to date, proton therapy is a promising option for patients who would benefit from the added locoregional disease control provided by reRT for recurrent or new primary breast cancer.

Comparison between the high-definition 3D exoscope and the operating microscope in head and neck reconstruction

The purpose of this study was to compare the three-dimensional (3D) operating exoscope (OE) with the conventional operating microscope (OM) in head and neck reconstruction. A retrospective cohort study was performed including 50 consecutive patients with no history of previous surgery or irradiation (32 male, 18 female; mean age 59.2 ± 13.3 years), who underwent free flap head and neck reconstruction using a 3D OE (n = 25; OE group) or conventional OM (n = 25; OM group). The mean total operative time was 8.0 ± 1.53 h in the OE group and 7.6 ± 1.52 h in the OM group (P = 0.86). The median (interquartile range) anastomosis time was 78.0 (63.0–91.5) minutes in the OE group and 90.0 (75.5–115.0) minutes in the OM group (P = 0.06). The final free flap survival rate was 100%. Only seven patients experienced a free flap reconstruction-related complication, and they were similarly distributed between the two groups (four in the OE group, three in the OM group; P = 0.68). Secondary outcomes (length of hospital stay, tracheostomy dependence, feeding tube dependence) were comparable in the two groups (P > 0.05). The 3D OE is a viable alternative to the conventional OM for performing standard head and neck free flap reconstructive procedures.

Epigenetic signature of ionizing radiation in therapy-related AML patients

Therapy-related acute myeloid leukaemia (t-AML) is a late side effect of previous chemotherapy (ct-AML) and/or radiotherapy (rt-AML) or immunosuppressive treatment. t-AMLs, which account for ∼10–20 % of all AML cases, are extremely aggressive and have a poor prognosis compared to de novo AML. Our hypothesis is that exposure to radiation causes genome-wide epigenetic changes in rt-AML. An epigenome-wide association study was undertaken, measuring over 850K methylation sites across the genome from fifteen donors (five healthy, five de novo, and five t-AMLs). The study predominantly focussed on 94K sites that lie in CpG-rich gene promoter regions. Genome-wide hypomethylation was discovered in AML, primarily in intergenic regions. Additionally, genes specific to AML were identified with promoter hypermethylation. A two-step validation was conducted, both internally, using pyrosequencing to measure methylation levels in specific regions across fifteen primary samples, and externally, with an additional eight AML samples. We demonstrated that the MEST and GATA5 gene promoters, which were previously identified as tumour suppressors, were noticeably hypermethylated in rt-AML, as opposed to other subtypes of AML and control samples. These may indicate the epigenetic involvement in the development of rt-AML at the molecular level and could serve as potential targets for drug therapy in rt-AML.

Easy and Safe Clamping of the Internal Jugular Vein and Internal Carotid Artery for End-to-Side Anastomosis in the Vessel-Depleted Neck

Background Damage to the vascular system resulting from radiotherapy and previous surgeries in patients with recurrent neck tumors has a negative impact on secondary reconstructions. In this study, we describe a simple method for occlusion of the great vessels of the neck in patients with difficult access to recipient vessels for anastomosis. Methods A 1 or 0 gauge silk ligature is placed at a circumference of 540 degrees around the vessel, holding the base of the suture with a fine hemostatic clamp exerting sufficient pressure to stop the blood flow in the vessel (internal carotid artery or internal jugular vein), to prepare the end-to-side anastomosis to the flap. Results From 90 head a neck reconstructions for oncologic patients using microvascular flaps performed between April 2011 and April 2021, 8 of them (8.8%) were performed in patients with multiple previous surgeries and/or radiotherapy, with lesion of the arterial thyrolyngopharyngofacial trunk and secondary recipient veins, being the internal carotid and internal jugular the only available recipient vessels in the neck. Conclusions Occlusion of the great vessels of the neck with a thick silk at 540 degrees held by a hemostatic clamp at its base is a safe and reproducible method for occlusion of these vessels to perform end-to-side anastomosis in patients with difficult vascular access in the neck without increasing the risk of endothelial damage and thrombosis from the anastomosis.

Clinical application of 192Ir High-Dose-Rate brachytherapy in metastatic lymph nodes of the neck

ObjectiveThe objective of this study was to investigate the safety and effectiveness of high-dose-rate brachytherapy as a treatment modality for recurrent or residual neck metastatic lymph nodes following external radiotherapy.Methods38 patients with 52 metastatic lymph nodes recurring or residual after previous external radiotherapy was completed to metastatic lymph nodes in the neck were collected from January 2019 to February 2022. High-dose-rate brachytherapy with 192Ir was performed with a prescribed dose of 20–30 Gy/1f (effective biological dose of 60–120 Gy), and imaging was performed at 1, 3, and 6 months after treatment to assess the local control rate and adverse effects of treatment.ResultsAll 38 patients received completed treatment, and they were followed up for 6 months. 52 patients with neck lymph node metastases had an objective response rate.(Complete response, CR + Partial response, PR) of 76.9%, which comprised 89.5% (34/38) for lymph nodes ≤ 3 cm and 42.9% (4/14) for > 3 cm, P = 0.028. P > 0.05 for CR + PR versus stable disease, SD + progressive disease, PD for lymph nodes between different subdivisions of the neck. Using the Radiation Therapy Oncology Group (RTOG) Acute Toxicity Scoring System, there were 6 cases of acute radioskin injuries of degree I and 4 cases of degree II with a 60% symptomatic relief rate.ConclusionsHigh-dose-rate brachytherapy serves as a safe and effective method in treating recurrent residual neck metastatic lymph nodes in the field after external radiotherapy, exerting tolerable adverse effects.

Efficacy and Safety of Autologous Stem Cell Transplantation Combined with Chimeric Antigen Receptor T-Cell Therapy in the Treatment of Refractory/Relapsed B-Cell Lymphoma

Background Autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell therapy (CART) are salvage therapies that are utilised for the treatment of relapsed or refractory (R/R) B-cell lymphoma. However, whether the combination therapy of ASCT and CART (ASCT-CART) can improve the survival of R/R B-cell lymphoma remains unknown. A im The objective is to explore the effectiveness and safety of ASCT-CART in the treatment of refractory/relapsed B-cell lymphoma and compare the effects of disease status before ASCT-CART on patient survival. Methods From October 2019 to October 2022, 49 patients with R/R B-cell lymphoma tract were enrolled. The male/female ratio was 1.2：1, with a median age of 40 years (range, 16-69 years).The diagnosis included diffuse large B-cell lymphoma (DLBCL) (n=31）, High-grade B-cell lymphoma(n=8), Primary mediastinal B-cell lymphoma (PMBCL) (n=7), Burkitt lymphoma (BL) (n=2) and Richer (n=1). Among them , stage III-IV accounted for 43/49 (87.8%) and GCB subtype 22/49 (44.9%)，and received a median of 7 cycles（3-14）of prior treatment, previous radiotherapy was 8/49 (16.3%), and previous other target CART patients were 20/49 (40.8%).The disease status of patients before ASCT-CART was 23 patients in complete remission, 17 patients in partial remission, 3 patients with stable disease, and 6 patients with progressive disease.Patients were treated with BEAM and fludarabine before ASCT. Autologous stem cells were transfused with D0, and the median number of CD34+ cells was 4.14*106/kg（range, 0.7-12.99*106/kg）. CART cells were transfused on D1, and the median infusion of CART cells was 2.06*106/kg（range, 0.07-9.5*106/kg）. Results In efficacy assessment at 3 months after treatment, the objective response rate (ORR) was 40/49(81.6%), and the complete response rate (CRR) was 38/49 (77.6%).After a median follow-up of 23.1 months, the median overall survival (OS) was not reached, with 1-year OS being 81.6%, 2-year OS being 76%, and 3-year OS being 72.3%（Figure 1A）. Median progression-free survival (PFS) was not reached, with 1-year PFS at 73.5%, 2-year FFS at 70.5%, and 3-year FFS at 66.6%（Figure 1B） . Neutrophil and platelet engraftment in all cases on median days 16 (range 10-62 days) and 16 (range 7-52), respectively.Grade 3 or higher cytokine release syndrome (≥grade 3 CRS) and immune efector cell-associated neurologic toxicity syndrome (≥grade 3 ICANS) events occurred in 22.4%（11/49） and 4.1%（2/49）of the patients, respectively.In the 3-month efficacy evaluation of CR group before ASCT-CART treatment, ORR was 21/23(91.3%) and CRR was 20/23(87.0%). ORR and CRR were 19/26(73.1%) and 18/26 (69.2%) in patients who did not reach CR before ASCT-CART treatment.The 3-year OS and 3-year PFS were 91.3% and 82.6% in CR group before ASCT-CART treatment（Figure 1C,D）. The 3-year OS and 3-year PFS in the non-CR group were 58.6% and 54.6% respectively（Figure 1C,D）. Patients in CR group before ASCT-CART treatment had significantly prolonged OS and PFS (P=0.0243) and OS (P= 0.0720). Summary/Conclusion The ASCT-CART therapy could enhance its the remission rate and long-term efficacy in the treatment of advanced relapsed/refractory B-cell lymphoma with controllable safety. Patients who were in remission before ASCT-CART therapy achieved a longer term remission after ASCT-CART cell therapy.

Efficacy and Safty of Stem Cell Mobilization with Etoposide +Cytarabine Plus G-CSF in Patients with Lymphoma at High-Risk of Mobilizing Failure

Objective：Sufficient peripheral blood stem cell (PBSC) mobilization is important for performing successful autologous stem cell transplantation (ASCT) in patients with lymphoma. However, the optimal mobilization strategy remains a matter of debate in lymphoma.The aim of the study was to explore efficacy and safety of PBSC mobilization using etoposide combined with Cytarabine (EA) plus G-CSF in patients with lymphoma at high-risk of mobilizing failure. Methods：This retrospective study explored efficacy and safety of PBSC mobilization using EA (etoposide 50~100 mg/m2 , qd d1~3; AraC 0.5 g/m2 , q12h d1~3) plus G-CSF (5 µg/kg/day, from d5 until the day of apheresis) in 81 patients with lymphoma at high-risk of mobilizing failure. As previously reported, patients were defined at high-risk of mobilizing failure if (i) previous collection attempts failed (no special instructions); (ii) previous extensive radiotherapy or a complete course of treatment had affected stem cell activity; or (iii) any of these conditions: advanced disease (2 lines of chemotherapy), refractory disease, extensive bone marrow involvement or cellularity &amp;lt;30% at the time of mobilization or age 65 years. Results：The mean total and first apheresis trial CD34+ cells collection was 20.37(range 1.08~138.96) and 18.56(range 0.1~138.96)×10^6 CD34+ cells/kg, respectively. Overall, 79(97.5%) patents harvested adequate mobilization (≥2×10^6 CD34+ cells/kg), while 65(80.2%) patients achieved optimal mobilization(≥5×10^6 CD34+ cells/kg). A single apheresis was sufficient to reached the target yield of adequate apheresis in 67(82.7%) patients on median 15th day (range 11~19). We observed acceptable hematological toxicity and exposure of antibiotic usage in 57 patients with a median of 4 days. No severe infections or mobilization-related mortality were observed. Conclusion：Our resluts suggest that EA plus G-CSF is an effective and safe PBSC mobilization strategy for patients with lymphoma, including those predicted as poor mobilizers. The outcome should be evaluated in a randomized study.

Pulmonary Lobectomy for Early-Stage Lung Cancer with Uniportal versus Three-Portal Video-Assisted Thoracic Surgery: Results from a Single-Centre Randomized Clinical Trial.

Video-assisted thoracic surgery (VATS) is a consolidated approach; however, there is no consensus on the number of ports leading to less postoperative pain. We compared early postoperative pain after uniportal and three-portal VATS lobectomy for early-stage NSCLC. In this randomized clinical trial, patients undergoing VATS lobectomy were randomly assigned to receive uniportal (U-VATS Group) or three-portal (T-VATS Group) VATS. The inclusion criteria were age ≤ 80 years and ASA < 4. The exclusion criteria were clinical T3, previous thoracic surgery, induction therapy, chest radiotherapy, connective tissue or vascular diseases, major organ failure, and analgesics or corticosteroids use. The postoperative analgesia protocol was based on NRS. Pain was measured as analgesic consumption; the secondary endpoints were intra- and postoperative complications, conversion rate, surgical time, dissected lymph nodes, hospital stay, and respiratory function. Out of 302 eligible patients, 120 were included; demographics were distributed homogeneously. The mean cumulative morphine consumption (CMC) in the U-VATS Group after 7 days was lower than in the T-VATS Group (77.4 mg vs. 90.1 mg, p = 0.003). Intraoperative variables and postoperative complications were comparable. The 30-day intercostal neuralgia rate was lower in the U-VATS Group, without reaching statistical significance. Patients undergoing U-VATS showed a lower analgesic consumption compared with the T-VATS Group; analgesic consumption was moderate in both groups.

Teprotumumab for the Treatment of Recalcitrant Thyroid Eye Disease.

Teprotumumab, an insulin-like growth factor 1 receptor monoclonal antibody, is FDA-approved to treat thyroid eye disease (TED). The initial clinical trials excluded patients with previous orbital irradiation, surgery, glucocorticoid use (cumulative dose >1 gm), or prior biologic treatment. Information on the use of teprotumumab for patients who failed prior therapy is limited. Our purpose is to characterize the efficacy of teprotumumab for the treatment of recalcitrant TED. This is a multicenter retrospective study of all patients treated with teprotumumab for moderate-to-severe TED after failing conventional therapy with corticosteroids, orbital radiation, surgical decompression, biologics, or other steroid-sparing medications. Treatment failure was defined as an incomplete response to or reactivation after previous treatment. Only patients who received at least 4 infusions of teprotumumab were included in the analysis. Primary outcome measures comprised proptosis response (≥2 mm reduction in the study eye without a similar increase in the other eye), clinical activity score (CAS) response (≥2-point reduction in CAS), and diplopia response (≥1 point improvement in Gorman diplopia score in patients with baseline diplopia) following treatment. Adverse events and risk factors for recalcitrant disease were also evaluated. Sixty-six patients were included in this study, 46 females and 20 males. Average age was 59.3 years (range 29-93). The mean duration of disease from TED diagnosis to first infusion was 57.8 months. The proptosis, CAS, and diplopia responses in this recalcitrant patient population were 85.9%, 93.8%, and 69.1%, respectively. Patients experienced a mean reduction in proptosis of 3.1 ± 2.4 mm and a mean improvement in CAS of 3.8 ± 1.6. Patients who underwent prior decompression surgery experienced a statistically significant decrease in diplopia response (46.7% vs. 77.5%, p = 0.014) and proptosis response (75.0% vs. 90.9%, p = 0.045) when compared with nondecompression patients. Additionally, there were no significant differences in proptosis, CAS, and diplopia responses between patients with acute (defined as disease duration <1 year) versus chronic (disease duration ≥1 year) TED. While most adverse events were mild to moderate, 4 patients reported serious adverse events related to persistent hearing loss. Patients with recalcitrant TED demonstrated a significant improvement after teprotumumab in each of the primary study outcomes. The degree of proptosis reduction, diplopia response, and CAS improvement in the recalcitrant group were similar to those of treatment-naïve patients from the pivotal clinical trials. Patients with a prior history of orbital decompression, however, demonstrated poor improvement in diplopia and less reduction in proptosis than surgery naïve patients. These results indicate that teprotumumab is a treatment option for the treatment of patients with TED recalcitrant to prior medical therapies.

INNV-02. USAGE TRENDS OF COLLAGEN TILE BRACHYTHERAPY FOR THE FIRST 1000 ORDERS

Abstract INTRODUCTION Collagen tile brachytherapy (CTBT) was cleared by the FDA in 2018 for all recurrent intracranial neoplasms and in 2020 for newly diagnosed intracranial neoplasms. We sought to describe usage trends of CTBT by evaluating the first 1000 consecutive orders since CTBT became commercially available in 2019 with respect to tumor type (glioma, brain metastasis, meningioma) and CTBT treatment setting (newly diagnosed, recurrence with prior radiation, recurrence without prior radiation). METHODS Commercial data was accessed using Salesforce, Inc. Coefficient of correlation (r2) was estimated as a measure of orders over time. 1000 orders were divided into 4 time cohorts (Cohort 1 for 1st 250 orders, Cohort 2 for 2nd 250 orders, Cohort 3 for 3rd for 250 orders and Cohort 4 for 4th 250 orders). Order proportions were compared among time cohorts using X2 tests. RESULTS Time period for 1000 orders among 93 centers was 1/23/19–5/11/23. Over these 17 completed yearly quarters there was a positive trend in ordering frequency (r2=0.97). Tumor type was known for 917 orders, of which 52.2% were glioma, 37.4% metastases, and 10.4% meningioma. Proportions of orders for tumor type did not change over time cohorts (p=0.26). Treatment setting was known for 816 orders, of which 80.3% were in recurrence with previous radiation, 14.3% newly diagnosed, and 5.4% recurrence without previous radiation. For glioma and meningioma, treatment setting did not change over time cohorts (p=0.5, p=0.3, respectively). However, for metastases, the proportion of orders for use in the newly diagnosed setting increased over time: 6.4% in Cohort 1, 19.2% in Cohort 2, 21.6% in Cohort 3, 34.7% in Cohort 4 (p&amp;lt; 0.001). CONCLUSION CTBT usage is increasing over time. Proportions of orders among tumor types (glioma, meningioma, metastases) has not changed. However, use of CTBT is increasing in the newly diagnosed setting for brain metastases.

RADT-30. PROTON THERAPY FOR RE-IRRADIATION OF RECURRENT GLIOMA

Abstract BACKGROUND Proton therapy may improve the side effect profile of re-irradiation for recurrent glioma by limiting the overlap with previous radiation dose received by the brain. Limited data exist regarding the outcomes or side effects after proton re-irradiation. METHODS We retrospectively reviewed the charts of 43 consecutive adult patients with glioma treated with uniform scanning or pencil beam scanning proton re-irradiation from June 2014-June 2022. Outcomes were estimated utilizing Kaplan-Meier analysis. RESULTS Median age of the cohort was 45 years (range 19-74). Initial histologic diagnosis was glioblastoma for 18 (42%), astrocytoma for 16 (37%), oligodendroglioma for 8 (19%) and diffuse glioma NOS for 1 (2%) patient. The median initial prescription dose was 60 Gy (range 54-61.2 Gy) with 86% receiving concurrent temozolomide. The median interval between initial radiation therapy (RT) and re-irradiation was 51 months (range 6-185 months). The median re-irradiation dose delivered was 37.5 cobalt gray equivalent (CGE) in 15 fractions (range 6-50.4 CGE in 2-28 fractions) with 34 patients receiving this dose fractionation. Concurrent systemic therapy included bevacizumab (8), chemotherapy (5), immunotherapy (2) or none (28). Overall, 40 (93%) finished the planned course and three stopped early given progression. Median survival was 11.5 months for the full cohort (95% confidence interval: 6.8-13.6 months). For patients with glioblastoma, median survival was 6.4 months (95%CI 5.0-13.5 months). For patients without glioblastoma, median survival was 11.6 months (95%CI 9.2-34.3 months). Twelve patients (28%) developed symptomatic pseudoprogression/radiation necrosis, with ten requiring increased steroids and four requiring bevacizumab. CONCLUSIONS Proton re-irradiation was well tolerated in patients with recurrent glioma, with 6.4 and 11.6 month median survival estimates for glioblastoma and non-glioblastoma histologies, respectively. Symptomatic pseudoprogression/radiation necrosis was common. Further study is needed to determine whether proton re-irradiation has improved tolerability compared to photons.

Even the presence of minimal changes in regional wall motion abnormalities with exercise stress echocardiography predicts MACE and all-cause mortality in patients with previous chest radiotherapy

Abstract Background Exercise stress echocardiography (ESE) is a non-invasive, radiation-free, and widely available technique that has demonstrated a reliable accuracy for the detection of coronary artery disease (CAD). Chest radiotherapy (RT) is associated with accelerated age-related atherosclerosis and fibrosis in a dose-dependent manner. ESE plays a role as a screening tool of RT induced heart disease, however, the prognostic value of changes in regional wall motion abnormalities in this population during ESE has not been evaluated. Methods This is a retrospective cohort study of breast cancer survivors treated with adjuvant RT that underwent ESE from 2000-2020 after treatment completion. Outcomes evaluated were: major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, revascularization and stroke); and all-cause mortality. A univariate analysis was performed to characterize the population. Continuous variables were presented as means ± standard deviation (SD) or median with quartile 1 and 3 (Q1, Q3), and categorical variables as numbers and percentages. A Cox regression model adjusted by age and cardiovascular risk factors was used to evaluate variables associated with outcomes, and a time to first event approach was used. A p-value of &amp;lt;0.05 was considered statistically significant. Results From 2000-2020, 507 patients, with a mean age 66 ± 10 years, underwent ESE at a median of 5.8 years after RT completion. The most prevalent comorbidities were dyslipidemia (59%), HTN (55%) and obesity (37%). 55% underwent RT for left-sided breast cancer and 45% for right-sided, and median RT dose was 6000 cGy. Baseline characteristics are presented in Table 1. Most patients underwent Bruce Protocol (92%). Patients exercised a mean time of 6.6 minutes achieving 7.3 METS and 109% of functional aerobic capacity (Table 2). At a median follow up of 7.8 years, 61 MACE events occurred. Predictors of MACE were double product, baseline and stress EF, baseline and peak regional wall motion abnormalities (RWMA), development of new ischemic RWMA, inability to reach 85% of maximum HR, and an abnormal EF response with stress after adjusting for age, HTN, DM, smoking history, dyslipidemia, obesity, prior MI and cancer staging (Fig 1). Predictors of all-cause mortality were METS, LV mass index, baseline and peak RWMA, development of new ischemic RWMA and an abnormal EF change with stress even after adjusting for variables described previously (Fig 2). Conclusions The development of new or worsening RWMA of just 2 segments with stress, was a significant predictor of MACE and all-cause mortality in a large cohort of breast cancer survivors undergoing multidisciplinary management including adjuvant RT. Special emphasis on management of cardiovascular comorbidities and closer surveillance are recommended for these patients.