Distant Progression Research Articles

APAVAC Immunotherapy for the Adjuvant Treatment of a Canine Mucosal Melanoma

An 11-year-old spayed female Beagle presented with tenesmus and was identified with a rectal wall mass. Diagnostic imaging (abdominal ultrasound and computed tomography) localised the mass in the right rectal wall and documented no evidence of metastatic disease. Subsequently, the dog underwent surgery for tumour excision. A histopathological diagnosis of melanoma was performed. To confirm the tumour histotype, immunohistochemistry was performed using anti-Melan A and anti-Ki67. Neoplastic cells exhibited focal Melan A immunoreactivity and widespread nuclear immunoreactivity for Ki67 with a Ki67 index of 27%. Adjuvant immunotherapy with APAVAC® was initiated. After APAVAC administration, no local or systemic acute adverse events were observed. Four pre- and post-contrast computed tomography (CT) studies were performed in an 18-month follow-up period every 4–5 months. Follow-up rectal palpation and conscious visualisation of the surgical site have also resulted in no macroscopic signs of tumour recurrence. The dog remains alive and with no clinical evidence of tumour recurrence and/or distant progression at the time of writing, therefore, surviving over 540 days from the diagnosis.

A hypoxia-activated and microenvironment-remodeling nanoplatform for multifunctional imaging and potentiated immunotherapy of cancer

Activatable theranostic systems combining precise diagnosis and robust immune activation have significant potential in cancer treatment. Herein, we develop a versatile nanoplatform integrating hypoxia-activatable molecular imaging with effective photoimmunotherapy for cancer treatment. Our molecular probe features turn-on near-infrared-II (NIR-II) fluorescence and photoacoustic signals in hypoxic tumor environments. It also induces hypoxia-triggered photodynamic and photothermal effects, promoting immunogenic cell death and activating the STING pathway, engaging both innate and adaptive immunity. The molecular probe is formulated with a vascular disrupting agent to amplify the hypoxia-responsive phototheranostic properties, on which M1-like macrophage membrane is camouflaged to shield against premature release while conferring cancer-targeting affinity. The activatable NIR-II fluorescence and photoacoustic imaging enable precise tumor delineation, while the enhanced phototherapy activates tumor-specific cytotoxic T cells, impeding both primary and distant tumor progression and providing protective immunity against rechallenge in 4T1 tumor-bearing female mice. This work advances activatable theranostic protocols for image-guided immunotherapy.

Survival and relapse patterns in patients of cranial versus extra-cranial oligometastases treated with stereotactic radiosurgery/stereotactic body radiation therapy and systemic therapy

Abstract Objectives To evaluate the outcome of patients with cranial (C) and extra cranial (EC) oligometastases treated with stereotactic radiosurgery (SRS)/stereotactic body radiotherapy (SBRT) and standard of care systemic therapy. Methods During the period 2018-2022, patients who received SBRT or SRS for oligometastases (≤5 lesions) in addition to systemic therapy were evaluated. PET-CT was done to categorize them as C or EC oligometastases. Local control, distant progression, progression free (PFS), overall survival (OS) and toxicity of the treatment were recorded. Results 43 patients received SBRT/SRS to 88 oligometastatic lesions. Eighteen patients had C metastases, 23 had EC metastases and 2 patients had both. 40/43 patients had received systemic therapy. At a median follow up of 13 months, median PFS was 14 months and 1 and 2 years OS was 83.2% and 67.4%. Local control with SRS was 92.8% and with SBRT was 86.3%. Distant failure in C Vs EC oligometastases was seen in 12/14 Vs 7/20 patients (p = 0.03). Median PFS was 30 months for EC and 6 months for C oligometastases (p = 0.003). 1 and 2 years OS was 89.6% and 82.7% for EC and 77.6% and 48.5% for C oligometastases (p = 0.21). One patient had grade 3 and 3 patients had grade 1 toxicity. Conclusions SRS and SBRT yielded high rates of local control with low toxicity. Compared to EC, patients with cranial oligometastases had higher distant relapses, poorer PFS and a trend towards worse survival. More studies with separate enrolment of patients with C and EC oligometastases are needed. Advances in knowledge Outcome of patients with cranial oligometastases is poorer than extra cranial metastases and hence the studies should be separately done in these two groups to assess the benefit of SRS/SBRT.

Minimally Invasive Image-Guided Percutaneous Irreversible Electroporation of Adrenal Metastases.

A single-center retrospective study was performed to evaluate the safety and efficacy of minimally invasive irreversible electroporation (IRE) to treat metastatic adrenal tumors. This single-center study, approved by the Institutional Review Board, retrospectively analyzed six patients who underwent image-guided percutaneous IRE for adrenal metastases. Pre-procedural imaging included CT, MRI and/or 18F-FDG PET-CT scans. Primary outcomes measures included technical success, efficacy and safety, while secondary outcome measures were local progression-free survival (LPFS), distant progression-free survival (DPFS) and overall survival (OS). Follow-up scans were scheduled post-procedure, and data analysis employed Excel, SPSS and R. Patients had diverse primary tumor origins including renal cell carcinoma (2/6), colorectal carcinoma (1/6), non-small cell lung carcinoma (1/6), leiomyosarcoma (1/6) and urothelial carcinoma (1/6). Adverse events were minimal, with only one grade 1 complication reported. Tumor characteristics revealed tumors close to critical structures, with a median pre-ablation size of 23mm. Technical success was achieved in all procedures. At first follow-up, one patient had complete response, one patient had partial response of the right adrenal gland and complete response of the left adrenal gland, two patients had partial response and two patients had stable disease. Local tumor progression occurred in two out of seven tumors with a median LPFS of 10.9months, and distant progression was observed in four out of six patients. Percutaneous, minimally invasive IRE shows promise as a safe treatment option for unresectable metastatic adrenal tumors, demonstrating potential effectiveness. However, further studies with larger patient cohorts are needed to confirm its safety and efficacy.

Cryoablation for treatment of peripheral lung metastases from colorectal cancer: a bicenter retrospective study.

To evaluate the oncological efficacy and complications of cryoablation (CA) in treating lung metastases from colorectal cancer (CRC) at the lung periphery. The inclusion criteria for this bicenter retrospective study included patients with histologically confirmed CRC, with radiologically confirmed lung metastases at the periphery of the lung (distance of less than or equal to 2 cm from the costal, diaphragmatic, or cervical pleura) treated with CA between January 2017 and June 2022. Patients with intra-parenchymal metastases or metastases close to the mediastinal pleura and patients without follow-up were excluded. Seventy-three patients were included (median age: 69 years, range 47.0-83.0; 38 males, 52.0%) with 113 metastases and 89 procedures. Technical success was achieved in all procedures. During follow-up (median 22 months), on a per metastasis basis, local recurrence occurred for 8/113 (7%) of the metastases in 7 patients at a median time of 19 months; 7 had concomitant distant recurrence. Local progression-free survival rates were 95% at 1 year and 89% at 2, 3, and 4 years. Distant progression occurred in 41/73 (56.2%) patients, significantly associated with a history of liver metastasis and synchronous lung metastasis (p < 0.05). The median chemotherapy-free survival was 14 (IQR (5.0-21.5)) months. Complications were predominantly mild or moderate, with a low incidence of severe complications. CA demonstrates high rate of local control and appears well-tolerated in the treatment of peripheral lung metastases from CRC. The procedure offers a viable therapeutic option, allowing patients a significant period without chemotherapy. Question Despite its advantages over surgery, data on cryoablation of metastases from colorectal cancer at the periphery of the lung are lacking. Findings Cryoablation enabled very good local control, with local progression-free survival rates of 95% at 1 year and 89% at 2, 3, and 4 years. Clinical relevance Cryoablation is an effective treatment for local tumor control of lung metastases from colorectal cancer at the periphery of the lung. The treatment is well tolerated and can provide patients with substantial relief from chemotherapy.

Phase I Study of Adjuvant Allogeneic GM-CSF-Transduced Pancreatic Tumor Cell Vaccine, Low Dose Cyclophosphamide, and SBRT followed by FFX in High-Risk Resected Pancreatic Ductal Adenocarcinoma

PurposeLocal and distant progression remain common following resection of resectable pancreatic ductal adenocarcinoma (PDAC) despite adjuvant multiagent chemotherapy. We report a prospective institutional phase I trial incorporating adjuvant GVAX vaccine, low-dose cyclophosphamide (Cy) and SBRT followed by FOLFIRINOX (FFX) among patients who underwent resection of high-risk PDAC. Patients and MethodsThe study design was a modified 3+3. Cohort 1 received 5-fraction SBRT to 33 Gy to the tumor bed and 25 Gy to elective nodes followed by 6 cycles of full dose FFX. After toxicity review, cohort 2 had SBRT and were switched to modified FFX (mFFX). Cohort 3 had 1 cycle of Cy/GVAX followed by SBRT, mFFX, and 4 cycles of maintenance Cy/GVAX with 6-month Cy/GVAX boosts until progression. Results19 patients were enrolled with a median follow-up of 36.2 months. To be eligible, patients were required to have close/positive margins (within ≤1 mm) (71%) and/or lymph node metastasis (79%). Overall, 63% of patients had both. In cohort 1, 67% of patients received 6 cycles of FFX; in cohort 2, 75% received 6 cycles of modified FFX. In cohort 3, 12 patients received the first dose of Cy/GVAX and SBRT with 10 individuals (83%) receiving 6 cycles of mFFX. Cohort 3 had acceptable levels of grade ≥3 thrombocytopenia, neutropenia, and diarrhea after two cycles of mFFX. Median OS/DFS for the overall cohort and cohort 3 was 36.2/18.2 months and 61.3/24.1 months, respectively. 1-year and 2-year OS for cohort 3 was 83%/75%, respectively. At last follow-up (median= x), 5 patients were alive (42%) in cohort 3. ConclusionThis is the first prospective trial to evaluate adjuvant GVAX, Cy, SBRT, and mFFX in resected PDAC patients with high-risk features. This combination regimen was well tolerated with limited toxicity and promising survival outcomes, warranting future studies to validate this regimen in the adjuvant setting.

RADT-15. THE ROLE OF STEREOTACTIC RADIOSURGERY IN WHO GRADE II MENINGIOMAS: RESULTS FROM A LARGE EUROPEAN MULTICENTER STUDY

Abstract BACKGROUND This study evaluates the outcomes of WHO grade II meningiomas treated with stereotactic radiosurgery (SRS) using a large, multi-institutional European database. We aim to investigate the long-term tumor control rate and morbidity associated with SRS. METHODS Data from 355 consecutive patients treated between 1992 and 2022 at 16 European radiosurgery centers were retrospectively analyzed. After excluding 40 patients due to loss to follow-up, results from 315 patients were included. Clinical and imaging data were independently collected by each center and uniformly entered into a multicenter database. RESULTS The median age of patients was 56 years, with 54% being female. The median follow-up duration was 46.3 ± 36.9 months. Tumors had prior surgical treatment and biopsy in 99% and 1% of cases, respectively. Tumors received previous radiotherapy or SRS in 27.4% of cases. SRS was performed due to local progression in 89.6% of cases, residual tumor in 6.4%, and distant progression in 4.0%. SRS characteristics included a median target volume of 5.1 cm³ and a median margin dose of 16 Gy (53.5% isodose). The 3-year local control rate was 72.0%, with a progression-free survival rate of 66.6% and an overall survival rate of 89.7%. Transient and permanent morbidity rates were 6.4% and 3.5%, respectively. Multivariate analysis identified previous radiotherapy and age as significant factors influencing these outcomes. CONCLUSIONS This study is the largest to date on SRS in WHO grade II meningiomas. Our data shows that SRS is a viable and safe treatment option for residual and recurrent WHO grade II meningiomas

Limited Effectiveness in Early Human Clinical Experience with Pulsed Electrical Field Ablation

PurposeTo evaluate oncological outcomes, abscopal effect, and adverse events of pulsed electrical field (PEF) ablation of tumors in the chest, abdomen, and pelvis. Materials & MethodsPEF ablations performed at an academic medical center between May 2023 - January 2024 were retrospectively analyzed . 11 patients (male/female: 4/7, age:58 ± 19) underwent 11 PEF sessions targeting 13 tumors (lung metastasis from solitary fibrous tumor (n=3) and colorectal carcinoma(CA) (n=1), osteosarcoma pleural metastases (n=2), hepatocellular CA (n=2),liver metastasis from colorectal CA (n=1)and leiomyosarcoma (n=1), metastatic melanoma to pancreas (n=1), metastatic retroperitoneal lymph node from endometrial CA(n=1), recurrence of endometrial CA in vaginal cuff(n=1)) with the goal of complete coverage (n=11/13) or debulking (n=2/13). The mean tumor diameter was 1.9 ± 1.0 cm (range, 0.4 – 3.3 cm). Cross-sectional imaging follow-up was 5.3 ± 2.2 months (range, 1.9 - 7.9 months). Oncological outcomes, abscopal effect, and adverse events categorized according to SIR guidelines were reported. ResultsOf 11 tumors underwent ablation for complete coverage, complete coverage was achieved for 1 (9%) and residual detected in 9 (81%). 10 of 11 patients (91%) showed either residual, local or distant progression within a median of 3 months. No abscopal effect was observed. There were 2 mild and 2 severe adverse events. ConclusionsPEF ablation showed a low rate of complete coverage (9%) and a high rate (91%) of residual, local or distant progression. No abscopal effect was observed within a median of 5.1 months after the ablation.

Outcomes of Patients With Five or More Brain Metastases Treated With Stereotactic Radiosurgery From 2014 to 2019: A UK Series

AimsTreatment with stereotactic radiosurgery/radiotherapy (SRS/SRT) is standard practice in selected patients with small numbers of brain metastases (BMs). It is less accepted in those with ≥5 BMs, due to the lack of a prospective evidence base. While randomised trials are ongoing, we present the experience of a single UK cancer centre in using SRS/SRT for patients with 5 or more BMs without whole brain radiotherapy (WBRT). Materials and methodsPatients undergoing treatment at a single centre between 2014 and 2019 were prospectively identified. All follow-up imaging was reviewed to identify any evidence of local failure or distant brain progression, which was analysed using a death-censored approach. ResultsA total of N = 88 patients were included, with a median of seven BMs (range: 5–37). Post-SRS/SRT toxicity events occurred in 42%, most commonly reliance on steroids for ≥4 weeks (36% of the cohort). Median survival was 10 months, with median freedom from local failure and distant brain progression of 12 and 8 months, respectively; none of these outcomes differed significantly by the number of BMs. Brain-directed salvage treatment was required after a median of 21 months, and was not significantly associated with the number of BMs. ConclusionSRS/SRT alone may have a role in the management of selected patients with multiple BMs. Since the number of BMs were not significantly associated with overall survival or disease control, the National Health Service (NHS) commissioning criteria should continue to be based on tumour volume.

Metastatic Malignant Pseudomyogenic Hemangioendothelioma: An Exceedingly Rare Entity That Challenges Conventional Paradigms.

Pseudomyogenic hemangioendothelioma (PMHE), a rare soft tissue tumor predominantly affecting young adults, often presents as multiple nodules in various tissue planes of a limb. Malignant transformation and metastatic disease are unusual and pose diagnostic and therapeutic challenges. A 17-year-old patient from Western India, with a history of recurrent excisions for a toe swelling presented to our center for evaluation and management. A below-knee amputation was performed, and histopathology revealed PMHE. Adjuvant therapy was deemed unnecessary given the borderline nature of the tumor. Shortly thereafter, he developed features of local recurrence and underwent above-knee amputation. An expert histopathological review confirmed the diagnosis and noted features of malignant transformation-progression to a higher grade with greater cytological atypia, confluent growth, and increased mitotic activity over time. Upon further distant progression in the lung, he was started on a palliative regimen of weekly paclitaxel, vinblastine, and propranolol but eventually succumbed to his illness. In contrast to conventional descriptions of low mitotic activity, minimal nuclear atypia, and absence of necrosis, our patient exhibited increased mitotic rates, nuclear atypia, and evolving necrosis in serial histopathological evaluations. The fulminant clinical progression within a short interval was also atypical. Our patient's clinical course underscores the need for meticulous histopathological and molecular characterization and vigilant clinical surveillance after resection in patients with PMHE. Providing the standard of care for malignant disease in the adjuvant setting is challenging owing to the rarity and the lack of treatment guidelines.

Prognostic significance of fludeoxyglucose positron emission tomography delta radiomics following bridging therapy in patients with large B-cell lymphoma undergoing CAR T-cell therapy.

Bridging radiation therapy (bRT) is increasingly being utilized prior to chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). It is unknown how the extent of cytoreduction during bRT impacts outcomes. We retrospectively reviewed patients with LBCL treated with bRT followed by CAR T-cell therapy. Metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax), SUVmean, and total lesion glycolysis (TLG) were extracted from F18-fluorodeoxyglucose positron emission tomography (PET) scans acquired prior to bRT and between completion of bRT and CAR T-cell infusion. Delta radiomics based on changes of these values were then calculated. The association between delta radiomics and oncologic outcomes [progression-free survival (PFS), freedom from distant progression (FFDP), and local control (LC)] were then examined. Thirty-three sites across 23 patients with LBCL were irradiated. All metabolically active disease was treated in 10 patients. Following bRT, median overall decreases (including unirradiated sites) in MTV, SUVmax, SUVmean, and TLG were 22.2 cc (63.1%), 8.9 (36.8%), 3.4 (31.1%), and 297.9 cc (75.8%), respectively. Median decreases in MTV, SUVmax, SUVmean, and TLG in irradiated sites were 15.6 cc (91.1%), 17.0 (74.6%), 6.8 (55.3%), and 157.0 cc (94.6%), respectively. Median follow-up was 15.2 months. A decrease in SUVmax of at least 54% was associated with improved PFS (24-month PFS: 83.3% vs. 28.1%; p = 0.037) and FFDP (24-month FFDP: 100% vs. 62.4%; p < 0.001). A decrease in MTV of at least 90% was associated with improved FFDP (24-month FFDP: 100% vs. 62.4%; p < 0.001). LC was improved in sites with decreases in SUVmax of at least 71% (24-month LC: 100% vs. 72.7%; p < 0.001). Decreases of MTV by at least 90% (100% vs. 53.3%; p = 0.038) and TLG by at least 95% (100% vs. 56.3%; p = 0.067) were associated with an improved complete response rate. bRT led to substantial reductions in MTV, SUVmax, SUVmean, and TLG. The relative extent of these decreases correlated with improved outcomes after CAR T-cell infusion. Prospective cohorts should validate the value of interim PET following bRT for quantifying changes in disease burden and associated prognosis.

The combination of transarterial chemoembolization and microwave ablation is superior to microwave ablation alone for liver metastases from colorectal cancer

ObjectivesThis study aimed to compare the combination therapy of transarterial chemoembolization (TACE) and microwave ablation (MWA) with MWA alone in treating liver metastases from colorectal cancer (LMCRC).Materials and methodsIn this retrospective study, a total of 251 patients with unresectable and not to chemotherapy responding LMCRC were included. Group A consisted of 184 patients (104 male and 80 females; mean age: 64 ± 11.4 years) with 442 metastases who received a combination of TACE and MWA. A total of 67 patients (49 male and 18 females; mean age: 63.2 ± 11.8 years) with 173 metastases patients were included in group B, who received only MWA. Parameters assessed were local tumor progression (LTP), hepatic distant tumor progression (hDTP), hepatic progression-free survival (hPFS), and overall survival (OS).ResultsThe rate of LTP was 4.9% in group A and 4.5% in group B (p-value: 0.062). The rate of hDTP was 71.7% and 83.6% for groups A and B (p-value: 0.81), respectively. The mean hPFS was 13.8 months (95% CI 10.9–16.8) for group A and 8.1 months (95% CI 6.1–10.1) for group B (p-value: 0.03). The median OS time for group A was 30 months (95% CI 26–34), with 1-, 2-, 3-, and 4-year OS rates of 84.2%, 61.1%, 40.8% and 31.3%, respectively. In group B however, the median OS time was 26 months (95% CI 18–34) with 1-, 2-, 3-, and 4-year OS rates of 82.3%, 53.2%, 34.6% and 28.2%, respectively (p-value: 0.67).ConclusionThe combination therapy of TACE and MWA is superior to the monotherapy of MWA for LMCRC, especially regarding hDTP, hPFS and OS.

Cisplatin-Containing Combinations Associate with Survival in Women from Appalachian Kentucky with Metastatic, Persistent, or Recurrent Uterine Cervix Cancer.

Background: Prior preclinical studies showed promising antitumor activity and an acceptable safety profile associated with radiopharmaceuticals for patients with metastatic, persistent, or recurrent uterine cervix cancers. Whether the addition of a radiopharmaceutical to chemotherapy would significantly increase progression-free survival in such patients is untested. Our retrospective study sought to associate the line of treatment and progression-free survival as benchmarks for next-generation radiopharmaceutical development. Methods: We grouped metastatic, persistent, or recurrent uterine cervix cancer patients not amenable to curable surgery or radiotherapy between 2002 and 2023 by the line of doublet, triplet, and quadruplet chemotherapy or another intervention. After the first-line treatment, patients were monitored for radiographic progression every three months for up to three years. The primary endpoints were the first and any second or third progression-free survival intervals. Results: A total of 127 patients contributed demographic, tumor, line of treatment, and outcome data with a median follow-up of 18 months (25-75% interquartile range: 9 to 37 months). After the first-line treatment, 113 patients had local or distant progression or died from any cause, most often death from the disease (67%). Median progression-free survivals were 5.5 months (95% confidence interval: 4.8-6.0 months), 5.3 months (95% confidence interval: 4.5-6.3 months), and 3.0 months (95% confidence interval: 2.1-3.7 months) for the first-, second-, and third-line treatments, respectively. For a first-line cisplatin-containing regimen, the median progression-free survival was 6.5 months (95% confidence interval: 5.5-7.7 months). Conclusions: This study highlights the limited efficacy of current treatments for metastatic, persistent, or recurrent uterine cancer patients. A five-month progression-free survival might serve as a benchmark for the development of novel therapies in clinical efficacy trials, such as radiopharmaceuticals.

Ultra–Low-Dose Radiation for Extranodal Marginal Zone Lymphoma of the Lung

PurposeDefinitive intent radiation therapy (RT) for early-stage mucosa-associated lymphoid tissue (MALT) lymphoma typically includes a dose of 24 to 30 Gy. While modest, these doses may have associated toxicity. For patients with indolent B-cell lymphoma, there is increasing support for the use of ultra–low-dose RT (ULDRT) using 4 Gy in 2 fractions as part of a response-adapted approach, as high rates of complete response have been documented. This paradigm has been prospectively evaluated in the management of orbital and gastric indolent B-cell lymphomas; however, there is limited data guiding the use of ULDRT for lung MALT. MethodsWe conducted a retrospective review of 20 patients at our institution with lung MALT treated with ULDRT as part of a response-adapted approach. Clinical variables including prior systemic therapy and symptoms were abstracted from the electronic health record. Responses were assessed using the revised Lugano criteria. ResultsAt a median follow up of 17 months following 4 Gy (IQR, 8-37 months), we observed 100% local control. Nineteen patients (95%) experienced a complete response. No patients with stage IE disease at RT (17/20; 85%) experienced distant progression. Nine patients (45%) were symptomatic prior to RT, with improvement or resolution of symptoms in 7 (7/9; 78%). One patient developed grade 2 pleuritic pain following RT, which resolved with a brief course of steroids. No other toxicities were noted. ConclusionsULDRT, given in a response-adapted approach, is effective and well tolerated by patients with lung MALT.

Associations between perceived interpersonal support and aggressiveness of care in the last month of life among patients with advanced cancer.

To determine quality of life (QoL) domains in the months leading up to death associated with the receipt of aggressive care in the last month of life among patients with advanced cancer. A multisite, prospective cohort study conducted from January 2010 to May 2015 of 59 patients with advanced cancer (distant metastases and/or progression of disease following at least first-line chemotherapy) and poor prognosis (≤ 6months) followed through death. At baseline, a median of 4months from death, the McGill Quality of Life Questionnaire measured overall QoL and four QoL domains (i.e., interpersonal support, physical well-being, psychological, and existential). Postmortem data were collected via medical chart review and nurse/caregiver report and combined to capture the aggressiveness of end-of-life (EoL) care in patients' last month of life. Aggressive EoL care was defined as any receipt of care in an intensive care unit, being on a ventilator, or chemotherapy in the last month of life. Patients with higher interpersonal support domain scores (i.e., rating the world as more "caring and responsive" to their needs and their felt support as more complete) received significantly less aggressive care in their last month of life (odds ratio = 0.39, 95% confidence interval 0.20 to 0.75, p = 0.004). Perceived interpersonal support is the only QoL domain assessed that was associated with aggressiveness of care in the last month of life for patients with advanced cancer. Prioritizing caring and responsive relationships for patients may decrease receipt of aggressive EoL care.

Osimertinib after definitive chemoradiotherapy in unresectable stage III epidermal growth factor receptor-mutated non-small-cell lung cancer: analyses of central nervous system efficacy and distant progression from the phase III LAURA study

Distant metastases in non-small-cell lung cancer (NSCLC) are a poor prognostic factor that negatively impact quality of life. The central nervous system (CNS) is a common site of distant progression in epidermal growth factor receptor-mutated (EGFRm) NSCLC. Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor recommended for advanced EGFRm NSCLC and as adjuvant treatment for resected EGFRm NSCLC. In LAURA (NCT03521154), osimertinib demonstrated statistically significant improvement in progression-free survival (PFS) versus placebo in unresectable stage III EGFRm NSCLC without progression during/following chemoradiotherapy (CRT). CNS efficacy and time to death or distant metastases (TTDM) analyses are reported here. Patients without progression during/following definitive platinum-based CRT were randomised 2 : 1 to receive osimertinib (80 mg daily) or placebo until progression [by blinded independent central review (BICR)] or discontinuation. The primary endpoint was PFS by BICR. CNS PFS by neuroradiologist BICR and TTDM by BICR were secondary endpoints. Overall, 216 patients were randomised (143 osimertinib, 73 placebo). Median CNS PFS by neuroradiologist BICR was not reached [95% confidence interval (CI) not calculable (NC)-NC] with osimertinib versus 14.9 months (95% CI 7.4 months-NC) with placebo; hazard ratio (HR) for CNS PFS: 0.17 (95% CI 0.09-0.32). CNS PFS analysis by investigator assessment was consistent with BICR assessment. The cumulative incidence of CNS progression at 12 months was 9% (95% CI 5% to 14%) with osimertinib and 36% (95% CI 24% to 47%) with placebo. There was clinically meaningful improvement in TTDM with osimertinib versus placebo; HR for TTDM: 0.21 (95% CI 0.11-0.38). The cumulative incidence of distant metastases at 12 months was 11% (95% CI 6% to 17%) with osimertinib and 37% (95% CI 26% to 48%) with placebo. Osimertinib demonstrated clinically meaningful improvements in CNS PFS and TTDM versus placebo, supporting osimertinib post-CRT as the standard of care in unresectable stage III EGFRm NSCLC.

Correlation of Needle Biopsy–Acquired Histopathologic Grade of Hepatocellular Carcinoma with Outcomes after Thermal Ablation

PurposeTo correlate preablation needle biopsy–acquired histopathologic grade of Liver Imaging Reporting and Data System (LI-RADS) 5 hepatocellular carcinoma (HCC) with postablation local tumor control rate, intrahepatic distant tumor progression–free survival, and overall survival. Materials and MethodsThis single-center, retrospective cohort study included adult patients with LI-RADS 5 HCC who underwent a preablation core needle biopsy within 3 months prior to thermal ablation from January 2015 to December 2022. Histopathologic grade from the needle biopsy was evaluated as predictor of local tumor control rate, intrahepatic distant tumor progression–free survival, and overall survival. Kaplan-Meier survival curves were compared using the Gehan generalized Wilcoxon test. ResultsThe study group comprised 133 patients (mean age, 67 years [SD ± 10]; 107 men) with LI-RADS 5 confirmed HCC, stratified into 18 poorly differentiated tumors (median follow-up, 27.7 months; interquartile range [IQR], 15.5–55.4 months) and 115 well-differentiated/moderately differentiated tumors (median follow-up, 29.2 months; IQR, 15.4–59.9 months). No difference in local tumor control rate was noted between the 2 cohorts (hazard ratio [HR], 1.16; 95% CI, 0.32–4.23; P = .898). There was significantly lower intrahepatic distant tumor progression–free survival after thermal ablation in the poorly differentiated cohort (HR, 2.54; 95% CI, 0.92–7.05; P < .001). The overall survival in the poorly differentiated cohort was also lower, although this did not reach statistical significance (HR, 1.77; 95% CI, 0.60–5.26; P = .202). ConclusionsPatients with needle biopsy–proven poorly differentiated LI-RADS 5 HCC had significantly lower intrahepatic distant tumor progression–free survival after thermal ablation compared with those with well-differentiated/moderately differentiated HCC.

Salvage stereotactic ablative body radiotherapy after thermal ablation of primary kidney cancer.

To evaluate the effectiveness and safety of salvage stereotactic ablative body radiotherapy (SABR) for recurrent renal cell carcinoma (RCC) after thermal ablation (TA). This study was a multi-institutional retrospective analysis of patients with recurrent RCC following TA who received SABR between 2016 and 2020. The primary study outcome was freedom from local failure, evaluated radiographically based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Distant failure, cancer-specific survival (CSS), overall survival (OS), treatment-related toxicity and renal function changes following SABR were the secondary outcomes. The Kaplan-Meier method was used to estimate freedom from local and distant failure, CSS and OS. Seventeen patients with 18 biopsy-confirmed RCCs were included, with a median (interquartile range [IQR]) age at time of SABR of 75.2 (72.6-68.7) years, a median (IQR) tumour size of 3.5 (1.9-4.1) cm and follow-up (reverse Kaplan-Meier method) of 3.36 (95% confidence interval [CI] 1.6-4.1) years. Six of the 17 patients had a solitary kidney. Five patients had failed repeat TA prior to SABR. The median (IQR) time from TA procedure to SABR was 3.03 (1.5-5.1) years. No patient experienced local progression, with a local control rate of 100%. Four patients, two with baseline metastatic disease, experienced distant progression. The distant progression-free survival, CSS and OS at 3 years were 72.1% (95% CI 51.9%-100%), 92.3% (95% CI 78.9%-100%) and 82.1% (95% CI 62.1%-100%), respectively. The median (IQR) glomerular filtration rate before SABR was 58 (40-71) mL/min, and at last follow-up, it was 48 (33-57) mL/min. No patient experienced grade 3+ toxicity or went on to develop end-stage renal disease. The results showed that SABR appears to be an effective and safe salvage strategy in patients with recurrent RCC following TA.

Chemotherapy switch for nonresponse or progression on neoadjuvant chemotherapy for pancreatic adenocarcinoma.

Patients with localized pancreatic adenocarcinoma who do not respond to neoadjuvant therapy present a challenge. We sought to define the characteristics and outcomes of those patients to guide clinical practice. Patients included were those without evidence of biochemical or radiographic response and no evidence of distant progression at the first reassessment after initiation of therapy. Of the 45 patients in the cohort, 23 (51.1%) proceeded to surgical exploration with all but one of those undergoing resection. The median overall survival of the study cohort was 28.6 and 48.6 months in those who underwent resection. A total of 13 patients (28.9%) underwent chemotherapy switch (CS) during their course of neoadjuvant therapy. The CS cohort demonstrated higher rates of radiologic progression (25% vs. 10%, p = 0.329), new or worse vascular involvement (58.3% vs. 30%, p = 0.082), and CA 19-9 increase (30.8% vs. 12.9%, p = 0.209) at initial re-staging. Despite this, overall survival was similar between the two groups (20.7vs. 28.7 months, p = 0.674). Non-responders to first-line neoadjuvant therapy have poor rates of curative-intent resection. However, resection should be undertaken when feasible. CS may be considered in patients who do not respond to first-line chemotherapy.

Evaluation of the efficacy and safety of toceranib phosphate in cats with macroscopic mammary adenocarcinoma.

Mammary tumours in cats are biologically aggressive. The standard of care relies upon wide surgical resection. Chemotherapy has been described in the macroscopic disease setting; however, limited efficacy has been shown. The aim of this study was to assess the efficacy of toceranib phosphate in macroscopic feline mammary tumours (FMTs). A total of 17 cats with cytologically or histopathologically confirmed mammary adenocarcinoma (gross disease) were prospectively enrolled. Toceranib phosphate was administered at a median dose of 2.77 mg/kg (range 2.3-3.2) PO q48 h. No corticosteroids or non-steroidal anti-inflammatory drugs (NSAIDs) were administered. Toxicity was graded according to Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events (VCOG-CTCAE) v1.1 criteria. The response was assessed after 1 month, following Response Evaluation Criteria In Solid Tumours (RECIST) criteria. Toxicity was observed in eight cats, with most instances being grade 1 or 2, which were managed with supportive care. Only one cat experienced grade 3 toxicity (anorexia), which resolved after a dose reduction. Clinical benefit was seen in 12 (64.7%) cats and an objective response was seen in six (35.2%) cats. One cat experienced complete response, five had partial response, six had stable disease and five had progressive disease. One cat showed distant progression (malignant pleural effusion) despite continued partial remission of the primary tumour. The median progression-free survival and median overall survival time were 91 days (range 30-158) and 145 days (range 31-234), respectively. Toceranib phosphate showed clinical benefit and a good safety profile in advanced or recurrent FMTs, offering a new alternative in the treatment of this disease; however, further prospective and randomised studies are required to further assess its efficacy. Interestingly, one cat developed distant metastases while the primary tumour showed partial response, suggesting that primary tumour and metastatic disease may not sustain the same sensitivity to toceranib.