Changes In Tumor Volume Research Articles

The Prognostic Significance of Early Tumor Volume Change in Rhabdomyosarcoma

Purpose: To describe early tumor volume change in patients with rhabdomyosarcoma (RMS) and investigate its association with overall survival (OS) and local failure. Methods: This retrospective study included patients diagnosed with Group III/IV RMS with available CT and/or MRI scans at two-time points: 1) pre-therapy and 2) early therapy (acquired during weeks 8 – 12 of chemotherapy). Relative volumetric change (RVC) was calculated as the percentage of: (early therapy – pre-therapy volume)/ (pre-therapy volume). Cox regression was used to identify variables associated with overall survival (OS). The Fine-Gray model was used to estimate local failure. Results: Eligible patients (n=55) had the following characteristics: median age at diagnosis: 9.6 years and median follow-up: 30.4 months. Most tumors were alveolar (61.8%) followed by embryonal (34.6%) and spindle cell/sclerosing (4%). The median RVC was -86.4% with larger decreases observed in alveolar vs. non-alveolar RMS (-89.4 vs. -69.8%, p=0.043). For embryonal and spindle cell/sclerosing RMS, all of which were FOXO1 fusion negative, RVC was independently associated with OS (Hazard Ratio for every 50% reduction in RVC [HRRVC]: 0.5, 95% Confidence Interval [CI]: 0.26 – 0.96, p=0.037) and local failure (HRRVC: 0.57, 95% CI: 0.33 – 0.99, p=0.049). The predominant pattern of failure in embryonal and spindle cell/sclerosing RMS was local and most were Group III. Conclusion: There was a greater reduction in tumor volume in alveolar vs. non-alveolar RMS. Early tumor volume reduction was associated with OS and local failure in embryonal or spindle cell/sclerosing RMS, all of which were confirmed FOXO1 fusion negative and had higher incidence of local compared to distant failures.

Transjugular Intrahepatic Portosystemic Shunt Is Associated With Better Waitlist Management of Liver Transplant Candidates With Hepatocellular Carcinoma.

Transjugular intrahepatic portosystemic shunt (TIPS) reduces portal hypertension complications. Its impact on hepatocellular carcinoma (HCC) remains unclear. We evaluated 42,843 liver transplant candidates with HCC from the Scientific Registry of Transplant Recipients (2002-2022). 4,484 patients with and without TIPS were propensity score-matched 1:3. Analysing wait-list changes in total tumor volume, HCC count, and alpha-fetoprotein levels, and assessing survival from listing and transplantation; TIPS correlated with a decreased nodule count (-0.24 vs. 0.04, p = 0.028) over a median wait period of 284 days (IQR 195-493) and better overall survival from listing (95.6% vs. 91.5% at 1year, p < 0.0001). It was not associated with changes in tumor volume (0.28 vs. 0.11cm³/month, p = 0.58) and AFP (14.37 vs. 20.67ng/mL, p = 0.42). Post-transplant survival rates (91.8% vs. 91.7% at 1year, p = 0.25) and HCC recurrence (5.1% vs. 5.9% at 5 years, p = 0.14) were similar, with a median follow-up of 4.98 years (IQR 2.5-8.08). While TIPS was associated with a reduced nodule count and improved waitlist survival, it did not significantly impact HCC growth or aggressiveness. These findings suggest potential benefits of TIPS in HCC management, but further studies need to confirm TIPS safety.

RADT-01. TUMOR VOLUME INCREASE AND NEED FOR RADIOTHERAPY PLAN ADAPTATION IN PEDIATRIC HIGH-GRADE GLIOMA AND DIFFUSE MIDLINE GLIOMA DURING A SIX-WEEK COURSE OF RADIOTHERAPY

Abstract BACKGROUND Pediatric High-Grade Glioma/ diffuse midline glioma (pHGG/DMG) growth during a six-week course of radiotherapy may precipitate geographical miss of target volumes and early disease progression. In a patient cohort, we retrospectively evaluated the evolution of tumor volumes during radiotherapy, the clinical need for plan adaptation, and potential correlation with local disease progression. METHODS Twenty-four pHGG/DMG patients (12M/12F, ages 4-20 years) with gross tumor volume (GTV) after debulking (n=7) or biopsy (n=17) received 30 fractions of Volumetric Modulated Arc Therapy within an adaptive radiotherapy-protocol. The GTV was defined by combined T1+FLAIR MRI sequence abnormalities. A 1-cm margin was applied for Clinical Target Volume (CTV). MRI-based target volume re-evaluation was performed at fraction 10 and 20, defining GTV increase &amp;gt;1mL as growth. The clinical need for plan adaptation was based on tumor volume changes. GTV increase and need for plan adaptation were evaluated against local progression-free survival (LPFS). RESULTS Median time between baseline MRI and radiotherapy start was 10 days (range 3-29). From baseline, GTV growth was observed in 7/24 patients at fraction 10, and in an additional 7/24 patients at fraction 20 (cumulative 14/24), corresponding to a mean volume increase of 21%/3.7mL (range [-7%/-2.7mL] to [+185%/24.4mL]) and 40%/8.7mL (range [-18%/-8.1mL] to [+329%/115.1mL]) after 10 and 20 fractions, respectively. At fraction 10 and 20, respectively 6 and 6 plans needed adaptation in a total of 11 patients. Baseline tumor volumes between patients with/without plan adaptation were equivalent. Median LPFS was 8.3 months (95%CI 8.0-12.7). No significant difference in LPFS was observed between patients with versus without GTV increase or plan adaptation. CONCLUSIONS Between MRI at baseline and at fractions 10 and 20, this adaptive radiotherapy protocol using 1-cm CTV margins demonstrated pHGG/DMG tumor volume increase with a clinical need for plan adaptations in 11/24 patients.

Predictive value of primary tumor volume change during concurrent chemoradiotherapy in patients with unresectable stage III non-small cell lung cancer

Background and purposeNo established early biomarkers currently exist to predict responses during concurrent chemoradiotherapy (CCRT) in patients with unresectable non-small cell lung cancer (NSCLC). This study investigated the potential of gross tumor volume (GTV) and its changes during CCRT as predictors of survival outcomes. Materials and methodsWe identified 227 patients with unresectable stage III NSCLC who underwent definitive CCRT followed by durvalumab between November 2018 and December 2022. GTV was defined as the volume of the primary tumor, assessed at two time points: before starting CCRT for initial planning (GTV1), and at the fourth week of CCRT for adaptive planning (GTV2). Both relative and absolute regressions between GTV1 and GTV2 were calculated. ResultsThe median GTV1 volume was 90 mL (range, 5–840 mL), and the median GTV2 volume was 64 mL (range, 1–520 mL), resulting in median absolute and relative regressions of 18.6 mL and 25.0 %, respectively. Among the GTV parameters, relative GTV regression exhibited the strongest predictive value, with an area under the curve (AUC) of 0.804 for in-field progression and 0.711 for overall progression. The 1-year progression-free survival rates for the high (>30 %), intermediate (0–30 %), and low (≤0%) relative regression groups were 88.0 %, 62.6 %, and 14.3 %, respectively (p = 0.006 for high vs. intermediate; p < 0.001 for intermediate vs. low). Additionally, GTV2 volume demonstrated stronger associations with survival outcomes than GTV1 volume. ConclusionRelative GTV regression was identified as a promising early predictor for patients with unresectable stage III NSCLC. Further development of a multi-parametric predictive model is warranted to guide patient-tailored therapeutic approaches.

Non-contrast-enhanced breast MRI for evaluation of tumor volume change after neoadjuvant chemotherapy

PurposeThree-dimensional contrast-enhanced magnetic resonance imaging (3D-Ce-MRI) is a most powerful tool for evaluation of neoadjuvant chemotherapy (NAC). However, the use of contrast agent is invasive, expensive, and time consuming, Thus, contrast agent-free imaging is preferable. We aimed to investigate the tumor volume change after NAC using maximum intensity projection diffusion-weighted image (MIP-DWI) and 3D-Ce-MRI. MethodWe finally enrolled 55 breast cancer patients who underwent NAC in 2018. All MRI analyses were performed using SYNAPSE VINCENT® medical imaging system (Fujifilm Medical, Tokyo, Japan). We evaluated the tumor volumes before, during, and after NAC. Tumor volume before NAC on 3D-Ce-MRI was termed Pre-CE and those during and after NAC were termed Post-CE. The observer raised the lower end of the window width until the tumor was clearly visible and then manually deleted the non-tumor tissues. A month thereafter, the same observer who was blinded to the 3D-Ce-MRI results randomly evaluated the tumor volumes (Pre-DWI and Post-DWI) using MIP-DWI with the same method. Tumor volume change between ΔCE (Pre-CE − Post-CE/Pre-CE) and ΔDWI (Pre-DWI − Post-DWI/Pre-DWI) and the processing time for both methods (Time-DWI and Time-CE) were compared. ResultsWe enrolled 55 patients. Spearman’s rho between ΔDWI and ΔCE for pure mass lesions, and non-mass enhancement (NME) was 0.89 (p < 0.01), 0.63(p < 0.01) respectively. Time-DWI was significantly shorter than Time-CE (41.3 ± 21.2 and 199.5 ± 98.3 respectively, p < 0.01). ConclusionsNon-contrast-enhanced Breast MRI enables appropriate and faster evaluation of tumor volume change after NAC than 3D-Ce-MRI especially for mass lesions.

Impact of joint peer review with a specialist radiologist in head and neck cancer radiotherapy planning.

e18059 Background: Head and neck oncology is heavily dependent on interpretation of radiology. This raises the question whether input from radiology should be formally scheduled as part of the radiotherapy contouring processes. Our aim was to assess the impact of this practice through qualitative and quantitative analysis. Methods: H &amp; N patients treated with radiotherapy between May-2022 and August-2023 were reviewed by a specialist HN radiologist. Incidence of changes in T, N, M and TNM-stage, change as defined by The RCR guidance: 'major' (change in gross tumour volume and/or high-dose clinical target volume, dose/fractionation) or 'minor' (change in intermediate or elective dose clinical target volumes or organs at risk), was recorded. We evaluated whether any of these changes were time dependent (Time interval between MDT to RT Peer Review). Other clinical variables: age, gender, primary diagnosis, tumour site, significant incidental findings, post-operative pTNM, post-operative disease status in adjuvant setting on planning imaging (NIRADS), need for additional imaging. We also recorded number of scans reviewed per patient, types of imaging studies reviewed, time taken for review and number of radiologist PA’s required. Retrospective analysis of a prospective database was performed. Results: 410 patients (252-definitive, 137-adjuvant, 21-palliative) were reviewed of which 51.5%-oropharynx followed by 26.8%-Larynx &amp; Hypopharynx. Mean age was 66.14 yrs (SD 11.46) and M:F was 4:1. Baseline and Therapy planning imaging was reviewed for 100% patients of which baseline included: MR (91.7%), CT (96.1%), US (34.1%), PETCT (31%) and therapy planning (62%-CECT, 19%-MR&amp;CT, 15%-CT, 4%-PETCT). In all patients (n=410), T/N/M/TNM-stage percentage upstage was 27/36.8/8.3/42.2% and in definitive cohort (n=252), it was 41.7/56.7/7.1/59.5%. Reviewing RT-planning Imaging in adjuvant cohort (n=137), 76.6% were NIRADS-1, 11.7% NIRADS-3/4/loco-regional disease and 11.7% distant metastasis. T/N/M/TNM-stage upstage was time dependent and the mean time interval between MDT to RT was higher in upstaged patients (p &lt;0.001). Overall percentage change in treatment plan: no/minor/major/palliative was 40.5/33.9/17.3/8.3% and in definitive cohort 30.2/42.1/20.6/7.1%. Change in plan was not dependent on mean time interval between MDT to RT. Average 10 patients (4 imaging studies/patient) were reviewed by radiologist in 1PA (time to review and peer review meeting time). Conclusions: Routine head and neck radiologist input in radiotherapy peer review is feasible and resulted in a number of major and minor changes to treatment. Inputs not only eased the contouring for oncologists but also lead to updating of current disease stage just prior to treatment. Overall, our results suggest that this is a practice changing step in the radiotherapy workflow which has a direct impact on patient management.

A reduction in tumor volume exceeding 65% predicts a good histological response to neoadjuvant chemotherapy in patients with Ewing sarcoma.

No consensus exists for tumor volume response criteria in patients with Ewing sarcoma. This study aimed to identify an optimal cutoff for predicting a good histological response by analyzing tumor volume changes and tumor necrosis after neoadjuvant chemotherapy. We performed a retrospective analysis of 184 Ewing sarcoma patients, analyzing tumor volume changes before and after neoadjuvant chemotherapy. Patients were divided into two groups based on histological response: good (tumor necrosis ≥ 95%) and poor (tumor necrosis < 95%) responders. The receiver operating characteristic (ROC) area under the curve (AUC) method was used to determine the optimal thresholds for predicting the histological response. Additionally, the prognostic value of this cutoff for relapse-free survival was assessed. Out of 184 patients, 83 (45%) had tumor necrosis ≥ 95%, while 101 (55%) had tumor necrosis < 95%. ROC analysis identified the optimal cutoff for a good histological response as over 65% tumor volume reduction (AUC = 0.69; p < 0.001). Patients with volume reduction of ≥ 65% had a higher likelihood of a good histological response than those with lesser reductions (p = 0.004; odds ratio = 2.61). Multivariable analysis indicated a correlation between poor histological response and reduced relapse-free survival (hazard ratio = 2.17; p = 0.01), while tumor volume reduction itself did not impact survival. We reported that a tumor volume reduction of ≥ 65% was able to predict a good histological response in Ewing sarcoma patients. We recommend preoperative tumor volume assessment to identify patients at greater risk for poor histological response who could benefit from more intensive chemotherapy protocols or additional radiotherapy.

Endovascular Embolization as a Stand-Alone Treatment of Head and Neck Paragangliomas with Long-Term Tumor Control.

The impact of therapeutic embolization as a stand-alone treatment of head and neck paragangliomas considered surgically high-risk remains insufficiently understood. The aim of this study was to investigate the procedural risks and long-term volumetric development in head and neck paragangliomas with high surgical risk following therapeutic endovascular embolization as a stand-alone treatment. A retrospective database review of patients who underwent endovascular embolization as primary treatment for head and neck paragangliomas lacking appropriate curative treatment options at our institution (from January 2000 to February 2023) was conducted. Tumor volumetric analyses were performed before embolization and during follow-up. To assess the changes in tumor volume over time, the measurements were performed after embolization, first at 6 months and then on a yearly basis up to 6 years (mean follow-up time was 33.7 ± 24.4 months). Subgroup analyses were conducted for vagal and jugular/jugulotympanic paragangliomas. A total of 32 head and neck paragangliomas in 28 patients (mean age, 56.1 years ± 16.5 [standard deviation]; 18 female) with therapeutic embolization as stand-alone treatment were evaluated, of which 11 were vagal paragangliomas, 15 jugular/jugulotympanic paragangliomas, and 6 carotid body tumors. After a mean follow-up duration of 33.7 ± 24.4 months, tumor control was achieved in 75%, with significant median tumor volume reduction at 6 months (P = .02, n = 21). Vagal paragangliomas responded the most to embolization with a significantly decreased median volume from 22.32 cm3 to 19.09 cm3 (P = .008, n = 8). Transient complications occurred in 3.4%. Therapeutic embolization as a stand-alone treatment offers a low-risk control of tumor growth in surgically high-risk lesions, with a significant reduction in tumor volume after treatment. Among the different subtypes, vagal paragangliomas exhibited the strongest and longest regression of the tumor volume.

Abstract PO3-07-10: Advanced CD8 ImmunoPET imaging predicts radiation response in primary TNBC

Abstract Background: Tumor immunology and immunosuppression has been observed to drive changes in intratumoral response to cytotoxic and immunotherapy in triple negative breast cancer (TNBC). While radiation therapy is standard of care for TNBC, there is a lack of research into the relationship between long term treatment response and CD8 immune infiltration in the context of a radiation resistant model. Positron emission tomography (PET) imaging allows for noninvasive monitoring of the tumor microenvironment that can precede changes in tumor volume, including approaches that allow for immune imaging of CD8 T-cell trafficking. Noninvasive PET imaging of radiation response has the potential to identify windows of enhanced response to secondary therapy and can guide interventional therapy. The goal of this study is to understand how radiation can prime the tumor microenvironment to be combined with other therapeutics in TNBC through changes in CD8 immune infiltration with [89Zr]-CD8 ImmunoPET imaging. Methods: Syngeneic parental 4T1 (radiation sensitive) and a developed radiation-resistant 4T1 sub-cell line were orthotopically injected into BALB/c mice (N = 5 control, N = 9-10 radiation treated for each model). After reaching a tumor volume of ~100 mm3, mice began treatment with 2 Gy fractionated radiation daily from day 0-5. On day 6, mice were injected with ~50 µCi of [89Zr]-CD8 minibody (IAB42) and imaged 24 hours post injection. The mean standardized uptake value (SUV) was quantified and normalized to heart SUV to extract out a tumor:heart SUVratio that describe the CD8 infiltration within tumors. Following imaging, tumors were either excised immediately for immunofluorescence against CD8 or monitored for longitudinal changes in tumor volume. A non-parametric T-test was used to assess for significance between groups. Results: In radiation sensitive 4T1 tumors, [89Zr]-CD8 ImmunoPET imaging indicated a 23% increase in CD8 immune infiltration, in radiation-treated tumors compared to control tumors on day 7 (p = 0.02). These immune alterations occurred prior to any changes in tumor volume (p = 0.63). Longitudinally, radiation treated tumors exhibited significant changes in tumor volume beginning on day 20 (p = 0.02), which is sustained until study endpoint on day 41 (p &amp;lt; 0.01). In radiation resistant 4T1 tumors, no significant change was observed in short term CD8 immune infiltration (p = 0.43) or in longitudinal tumor volume (p = 0.31) in response to radiation therapy, when compared to untreated tumors. Conclusions: [89Zr]-CD8 ImmunoPET imaging reveals significant increases in CD8 immune infiltration that is predictive of eventual response to radiation therapy in radiation sensitive models of TNBC. [89Zr]-CD8 PET imaging of radiation therapy response has the potential to increase the efficacy of precision medicine and prime the tumor microenvironment for secondary therapeutics, thereby improving tumor kill and reducing patient toxicity. Citation Format: Patrick Song, Shannon Lynch, Chloe DeMellier, Alessandro Mascioni, Fang Jia, Anna Sorace. Advanced CD8 ImmunoPET imaging predicts radiation response in primary TNBC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-07-10.

Abstract PO4-17-06: Real World Data: A single institute experience with neoadjuvant endocrine therapy for ER+ breast cancer — clinical response rates, clinical predictors of response and long-term outcomes following breast conserving surgery

Abstract Background: Neoadjuvant endocrine therapy (NET) in postmenopausal women (PMW) with large or locally advanced oestrogen receptor (ER)-rich breast cancer allows more women to be treated by breast-conserving surgery (BCS). A comprehensive analysis of the factors affecting clinical response to NET and the long-term safety of this strategy has been studied. Patients: A retrospective cohort was studied of 435 PMW (median age: 77 years; range: 50-98) with ER-positive breast cancer treated with NET (aromatase inhibition) (median duration: 6.8 months; range 3-43 months), between 2001-15. Clinical response was monitored throughout NET treatment with periodic 3D ultrasound measurements of the primary tumour. All patients went on to have surgery, 55% had adjuvant radiotherapy and all had adjuvant ET for at least 5 years. All patients had routine follow-up (median follow-up 12.3 years). To-date, this represents the largest cohort of patients treated with &amp;gt;3 months NET. Results: Clinical response to NET was excellent, with only 3.2% of tumours progressing on-treatment based on RECIST 1.1 criteria. Mean percentage reduction in tumour on NET was 71%. Response rate (partial/complete response) was 59% and response continued until 12 months and then levelled off. Following NET, over 92% of patients were suitable for BCS and 61% achieved clinical TNM down-staging. Multivariate analysis revealed that only ER level (response highest in patients with Allred scores 7 and 8), and percentage change in tumour volume by 6 weeks were significant predictors of overall clinical response to NET. Clinical response to NET was not associated with node status or tumour grade. BCS following NET had a local disease control rate of 89% (95%CI±0.06) at 10 years, but actuarial local recurrence at 10 years was only 7% in those having radiotherapy compared with 30% in the group who did not receive radiotherapy (P&amp;lt; 0.0001). In addition, the overall recurrence rate (P=0.028) was improved by radiotherapy irrespective of nodal status. Radiotherapy did not improve overall breast cancer-specific survival (BCSS). Systemic recurrence and BCSS was higher with greater nodal involvement. Most patients in this study died of other causes (14-year crude all-cause mortality was 71%). Conclusion: NET followed by BCS is an effective strategy in PMW with ER-rich breast cancer. Excellent clinical response rates are seen even in women with node-positive or high-grade disease. Less than 5% showed evidence of progression. Early response to NET predicts for long-term tumour volume reduction and NET can achieve continued tumour shrinkage for up to 1 year. NET followed by BCS appears a safe treatment approach and offers good long-term outcomes when BCS is followed by adjuvant radiotherapy. Citation Format: Arran K Turnbull, Carlos Martinez-Perez, Charlene Kay, Rebecca Swan, Lorna Renshaw, J Michael Dixon. Real World Data: A single institute experience with neoadjuvant endocrine therapy for ER+ breast cancer — clinical response rates, clinical predictors of response and long-term outcomes following breast conserving surgery [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-17-06.

Abstract PO5-07-03: Integrating mechanism-based and data-driven modeling to predict the response of triple negative breast cancer to therapy

Abstract Introduction Neoadjuvant chemotherapy (NAC) is the standard-of-care (SOC) for patients with locally advanced triple-negative breast cancer (TNBC) [1]. Unfortunately, only about half of TNBC patients achieve a pathological complete response (pCR) at the completion of NAC [2]. With the recent FDA approval of immunotherapy, the response rate improved by about 8% [3]. To try to further improve NAC response rates, we build upon methods that predict treatment response to optimize interventions and outcomes. Our previous studies have demonstrated that excellent predictive accuracy of TNBC response to NAC was achieved through calibrating mechanism-based models to both pre- and on- treatment imaging data [4]. However, by requiring on-treatment imaging data, therapy optimization can only occur after a patient begins NAC. Here, our goal is to relax the requirement of on-treatment imaging data such that we can predict, and potentially optimize, a patient’s response to NAC before initiating it. We will accomplish this through combining data-driven approaches with mechanism-based modeling to obtain spatiotemporal predictions of tumor response prior to NAC. More specifically, we integrate a reaction-diffusion equation based mathematical model with a U-Net based convolutional neural network (CNN). Methods The reaction-diffusion equation models the development of tumor cellularity over time as the sum of tumor cell diffusion, controlled by a fixed diffusivity, and tumor cell proliferation, controlled by a calibrated net proliferation rate. The net proliferation rate implicitly accounts for both proliferative and drug induced death effects. We calibrated the net proliferation rates in this model on a patient-specific basis for 128 patients from the ARTEMIS trial (NCT02276443) using three imaging timepoints – pre- (V1), post two cycles (V2), and post four cycles (V3) of A/C. We then employed a CNN to characterize the relationship between the calibrated net proliferation rates and the pre-treatment imaging data. The CNN takes pretreatment imaging inputs of the apparent diffusion coefficient map, percent enhancement maps from the dynamic contrast enhanced MRI timecourse, and precontrast T1 map. The CNN outputs an estimate of the calibrated net proliferation rate which can be used to run the mathematical model forward in time to predict cellularity maps at V2/3. In training the CNN, our loss considers both the concordance correlation coefficient (CCC) and the normalized root mean square error (NRMSE). We calculated loss on the net proliferation rate predictions as NRMSE with a CCC penalty to aid in characterizing the non-Gaussian distribution of the net proliferation rate. We calculated loss on the cellularity predictions as the CCC between predicted and measured voxel-wise cellularity. The CNN was trained using the Adam optimizer and a fivefold cross validation with a withheld test set of 26 patients. Results Using the CNN predictions to forward run the mechanism-based model in time to V3 we calculated change in total tumor cellularity and volume from V1 to V3. In the test cohort, we obtained CCC values between the predicted and measured changes of 0.95 and 0.91 for cellularity and volume, respectively. Discussion and summary Through integrating mechanistic modeling and deep learning, we can accurately predict the spatiotemporal development of TNBC response to NAC using only pretreatment imaging data. We will build upon these results by expanding our model to include separate proliferation and drug induced death terms to allow for therapy intervention and optimization. Additionally, we will incorporate other pretreatment data types including genetic data. [1] Liedtke et al., J of Clin Oncol, 2008. [2] Spring et al., Clin Cancer Res, 2020. [3] Schmid et al., NEJM, 2020. [4] Wu et al., Cancer Res, 2022. Citation Format: Casey Stowers, Chengyue Wu, Sidharth Kumar, Zhan Xu, Clinton Yam, Jong Bum Son, Jingfei Ma, Jonathan Tamir, Gaiane Rauch, Thomas Yankeelov. Integrating mechanism-based and data-driven modeling to predict the response of triple negative breast cancer to therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-07-03.

Using three-dimensional model-based tumour volume change to predict the symptom improvement in patients with renal cell cancer

In our recent study, we explored the efficacy of three-dimensional (3D) measurement of tumor volume in predicting the improvement of quality of life (QoL) in patients suffering from renal cell cancer (RCC), who were treated with axitinib and anti-PD-L1 antibodies. This study encompassed 18 RCC patients, including 10 men and 8 women, with an average age of 56.83 ± 9.94 years. By utilizing 3D Slicer software, we analyzed pre- and post-treatment CT scans to assess changes in tumor volume. Patients' QoL was evaluated through the FKSI–DRS questionnaire. Our findings revealed that 3D models for all patients were successfully created, and there was a moderate agreement between treatment response classifications based on RECIST 1.1 criteria and volumetric analysis (kappa = 0.556, p = 0.001). Notably, nine patients reported a clinically meaningful improvement in QoL following the treatment. Interestingly, the change in tumor volume as indicated by the 3D model showed a higher area under the curve in predicting QoL improvement compared to the change in diameter measured by CT, although this difference was not statistically significant (z = 0.593, p = 0.553). Furthermore, a multivariable analysis identified the change in tumor volume based on the 3D model as an independent predictor of QoL improvement (odds ratio = 1.073, 95% CI 1.002–1.149, p = 0.045).In conclusion, our study suggests that the change in tumor volume measured by a 3D model may be a more effective predictor of symptom improvement in RCC patients than traditional CT-based diameter measurements. This offers a novel approach for assessing treatment response and patient well-being, presenting a significant advancement in the field of RCC treatment.

Impact of Transjugular Intrahepatic Portosystemic Shunt on Hepatocellular Carcinoma: Prospective Cohort of Liver Transplant Candidates’ Analysis

Impact of Transjugular Intrahepatic Portosystemic Shunt on Hepatocellular Carcinoma: Prospective Cohort of Liver Transplant Candidates’ Analysis

1560: Changes in tumour volume before and during ocular proton beam therapy

1560: Changes in tumour volume before and during ocular proton beam therapy

1059: Predictive value of tumor volume change during chemoradiotherapy in non-small cell lung cancer

1059: Predictive value of tumor volume change during chemoradiotherapy in non-small cell lung cancer

Effects of bipolar irreversible electroporation with different pulse durations in a prostate cancer mouse model.

Irreversible electroporation (IRE) is a non-thermal ablation technique for local tumor treatment known to be influenced by pulse duration and voltage settings, affecting its efficacy. This study aims to investigate the effects of bipolar IRE with different pulse durations in a prostate cancer mouse model. The therapeutic effectiveness was assessed with in vitro cell experiments, in vivo tumor volume changes with magnetic resonance imaging, and gross and histological analysis in a mouse model. The tumor volume continuously decreased over time in all IRE-treated groups. The tumor volume changes, necroptosis (%), necrosis (%), the degree of TUNEL-positive cell expression, and ROS1-positive cell (%) in the long pulse duration-treated groups (300μs) were significantly increased compared to the short pulse duration-treated groups (100μs) (all p < 0.001). The bipolar IRE with a relatively long pulse duration at the same voltage significantly increased IRE-induced cell death in a prostate cancer mouse model.

Optimizing Treatment Quality in Head and Neck Cancer Therapy: Impact of Adaptive Intensity-Modulated Radiotherapy on Plan Quality and Tumor Volume Changes

Objective: This research analyses whether volumetric changes and PTV shifting affect adaptive intensity-modulated radiotherapy (IMRT) plan quality and head and neck cancer therapy. Methods: The research was carried out at the Sohag Cancer Centre in Egypt, including a sample of 36 individuals diagnosed with head and neck squamous cell carcinoma (HNSCC). Patients were chosen on the basis of the following criteria: locally progressed and node-positive malignancy, oropharyngeal cancer, oral cavity cancer, and unknown primary. The research used dynamic intensity-modulated radiation therapy (D-IMRT) to establish treatment plans and Siemens SOMATOM DEFINITION CT scanners to acquire 3D anatomical images. A range of 1.64 to 2.12 Gy was observed for the median dosage per fraction. Using the conformance index (CI) and the homogeneity index, the quality of the plan was assessed (HI). The threshold for statistical significance was set at 0.05. Results: The study analysed patients with unilateral and bilateral HNSCC tumors, with a majority having bilateral tumors. The findings demonstrated that the tumor PTV was significantly reduced as a consequence of the suggested adaptive radiation techniques. Both the homogeneity index and the conformity index were used to evaluate the plan's quality (HI). The maximal homogeneity index (HI) was reached after 7 and 14 fractions, respectively. The positive correlation between PTV reduction and CI after 7 fractions, while a negative correlation found after fractions 14 and 21. It was also shown that HI is positively correlated with PTV changes after 7 and 14. Conclusion: The use of adaptive radiotherapy in intensity-modulated radiation therapy (IMRT) treatment planning improves plan quality and decreases error rates due to tumor margin movement. Following radiation fractions, PTV shifting affects the homogeneity index (HI).

Abstract CT106: First-in-human phase 1 study of paclitaxel-eluting PTM-101 film in subjects with borderline resectable or locally advanced pancreatic cancers

Abstract Background Unlike many other types of cancer, improvements in the treatment of pancreatic cancer have been very limited, in part due to the inability to deliver chemotherapy to the tumor at efficacious concentrations for a prolonged time. PTM-101 is a novel biodegradable film containing paclitaxel and is designed to continuously release high concentrations of paclitaxel precisely to the site of a pancreatic tumor over one month. Methods This first in human study was conducted at one center in Australia to assess the safety, toxicity, and surgical feasibility of a single administration of PTM-101 containing 100 mg of paclitaxel. PTM-101 was sutured directly onto the pancreatic surface overlying the tumor by a surgical oncologist using standard laparoscopic equipment during a disease-staging assessment. Approximately 3 weeks after PTM-101 placement, all participants began standard of care therapy which included mFOLFIRINOX. This study enrolled 3 subjects that had treatment naïve, borderline resectable or locally advanced, pancreatic adenocarcinoma. Subjects were monitored closely for local and systemic toxicities, as well as for preliminary signals of efficacy. An independent central imaging lab reviewed CT scans to determine changes in tumor volume. Results PTM-101 was successfully implanted over the tumor site in all three subjects. In all cases, there were no adverse events reported during the procedure. Overall, PTM-101 was well tolerated with a total of five Grade 1 adverse events judged at least possibly related to the procedure or the mFOLFIRINOX. No serious adverse events (SAEs) or deaths occurred. Paclitaxel was undetectable in the circulation at all time points. Subjects were followed for 6 months. Best overall response rate according to RECIST was stable disease (2 subjects) and partial response (1 subject). An independent analysis showed that all tumors had a reduction in size in the anterior/posterior diameter, which was consistent with unidirectional paclitaxel release from PTM-101. Two of the 3 subjects had a &amp;gt;30% tumor volume reduction, importantly, with the initial decrease in tumor size detected prior to mFOLFIRINOX. Conclusion PTM-101 was readily implanted during diagnostic laparoscopy and was well tolerated with no SAEs or deaths reported during 6 months of follow up. This study demonstrated that a PTM-101 implant was surgically feasible, safe, resulted in no systemic paclitaxel exposure, and caused a tumor size reduction in all 3 subjects. Additional studies may demonstrate the potential for PTM-101 to be a first-line adjunct prior to neoadjuvant therapy in treatment naïve, borderline resectable or locally advanced, pancreatic cancer. Citation Format: Charles Pilgrim, Marty Smith, Ee-Jun Ban, Samantha Ellis, John Zalcberg, Benjamin Markman, Margaret Lashof-Sullivan, Laura Indolfi. First-in-human phase 1 study of paclitaxel-eluting PTM-101 film in subjects with borderline resectable or locally advanced pancreatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT106.

Adapt-On-Demand: A Novel Strategy for Personalized Adaptive Radiation Therapy for Locally Advanced Lung Cancer

Real-time adaptation of thoracic radiation plans is compelling because offline adaptive experiences show that tumor volumes and lung anatomy can change during therapy. We present and analyze a novel adaptive-on-demand (AOD) workflow combining online adaptive radiation therapy (o-ART) on the ETHOS system with image guided radiation therapy delivery on a Halcyon unit for conventional fractionated radiation therapy of locally advanced lung cancer (LALC). We analyzed 26 patients with LALC treated with the AOD workflow, adapting weekly. We timed segments of the workflow to evaluate efficiency in a real-world clinic. Target coverage and organ at risk (OAR) doses were compared between adaptive plans (ADP) and nonadaptive scheduled plans (SCH). Planning robustness was evaluated by the frequency of preplanning goals achieved in ADP plans, stratified by tumor volume change. The AOD workflow was achievable within 30 minutes for most radiation fractions. Over the course of therapy, we observed an average 26.6% ± 23.3% reduction in internal target volume (ITV). Despite these changes, with o-ART, ITV and planning target volume (PTV) coverage (V100%) was 99.2% and 93.9% for all members of the cohort, respectively. This represented a 2.9% and 6.8% improvement over nonadaptive plans (P < .05), respectively. For tumors that grew >10%, V100% was 93.1% for o-ART and 76.4% for nonadaptive plans, representing a median 17.2% improvement in the PTV coverage (P < .05). In these plans, critical OAR constraints were met 94.1% of the time, whereas in nonadaptive plans, this figure was 81.9%. This represented reductions of 1.32 Gy, 1.34 Gy, or 1.75 Gy in the heart, esophagus, and lung, respectively. The effect was larger when tumors had shrunk more than 10%. Regardless of tumor volume alterations, the PTV/ITV coverage was achieved for all adaptive plans. Exceptional cases, where dose constraints were not met, were due to large initial tumor volumes or tumor growth. The AOD workflow is efficient and robust in responding to anatomic changes in LALC patients, providing dosimetric advantages over standard therapy. Weekly adaptation was adequate to keep pace with changes. This approach is a feasible alternative to conventional offline replanning workflows for managing anatomy changes in LALC radiation therapy.

Predicting survival of patients with advanced hepatocellular carcinoma receiving combination targeted immunotherapy: an evaluation of volumetric imaging parameters.

To evaluate the potential of volumetric imaging in predicting survival of advanced hepatocellular carcinoma (HCC) patients receiving immunotherapy. Retrospective analysis included 40 patients with advanced HCC who received targeted immunotherapy. Baseline and follow-up contrast-enhanced abdominal computed tomography (CT) scans were analyzed. The largest tumor was chosen as the index lesion. Viable tumor volume (qViable) and percentage tumor viability (%Viability) were calculated. Response Evaluation Criteria in Solid Tumors (RECIST) and Tumor volume change after treatment (qRECIST) were measured. Associations with overall survival (OS) were assessed. Cox regression analysis assessed the association between variables and overall survival (OS). A new prognostic stratification system was attempted to categorize patients based on significant predictors of OS. Patients with a baseline %viability > 69% and %viability reduction ≥ 8% were classified as better prognosis. Patients were stratified into better, intermediate and worse prognosis groups based on baseline %viability > 69% and ≥ 8% %viability reduction (better prognosis); baseline %viability ≤ 69% and < 8% %viability reduction (worse prognosis); remainder were intermediate prognosis. Patients with baseline %Viability > 69% and %Viability reduction ≥ 8% showed significantly higher OS. Multivariate analysis confirmed %Viability and %Viability reduction as significant predictors of OS. A prognostic stratification system using these parameters stratified patients into better, intermediate and worse prognosis groups, with the better prognosis showing highest OS. Most patients (97.5%) had stable disease by RECIST while the prognostic model re-classified 47.5% as better prognosis, 37.5% intermediate prognosis, and 15% worse prognosis. Volumetric parameters of %Viability and %Viability reduction predict OS in HCC patients undergoing immunotherapy.