Post-treatment Response Research Articles

Assessment of quality of voice after 3D conformal hypofractionated radical radiotherapy in early-stage glottic cancer: A prospective study

ABSTRACT Purpose: The purpose of this study was to evaluate the short-term outcomes in terms of oncological outcomes, toxicities, and impact of quality of voice on livability of early glottic cancer (EGC) (T1) patients after hypofractionated radiotherapy. Material and Methods: 30 patients of early glottic carcinoma, staged cT1a-T1bN0M0 with Eastern Cooperative Oncology Performance Status (ECOG PS ≤ 2). Exclusion criteria included ECOG PS > 2, T2–T4 disease, and any other head and neck malignancy. Voice Handicap Index-10 (VHI-10) was used to score voice outcomes of patient’s pre- and post-radiation. Results: All the subjects were predominantly smokers (80%) having hoarseness of voice as the most common presenting complaint (76.7%) followed by dry cough (13.3%) and foreign body sensation (10%). On posttreatment response assessment, there has been a significant reduction in VHI-10 scores from pre-radiotherapy (RT) to 6, 12, and 24 weeks post-radiation completion in all three domains (functional, emotional, and physical), as well as total scores, with a significant P value (<0.05) being observed. Conclusion: The use of modest hypofractionated regimen (63 Gy in 28 fractions) in patients of early glottic disease (T1a and T1b) posttreatment completion provides good oncological outcomes with better quality of voice being observed.

Chlormethine gel in combination with other therapies for treatment of mycosis fungoides: a review with patient cases.

Topical chlormethine gel has been approved as monotherapy for treatment of adult patients with mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma. In clinical practice, chlormethine gel is often combined with other skin-directed or systemic therapies to optimize response and target recalcitrant lesions. Positive outcomes with combination regimens using chlormethine gel and topical corticosteroids, phototherapy, retinoids, methotrexate, or interferon-α have been reported in literature. However, there are no treatment guidelines on the use of combination regimens with chlormethine gel. To provide real-world evidence and guidance on the use of chlormethine gel combination regimens, several cases of patients treated with chlormethine gel combined with phototherapy (n = 5), retinoids (n = 16), or mogamulizumab (n = 3) are presented. These different combination regimens showed promising results. Most patients had a complete or partial response following treatment and the combinations were well-tolerated over extended treatment periods. Patients receiving chlormethine gel with retinoids had long-term periods of remission, even after treatment discontinuation. Durations of response of up to 3 years were observed in these patients. This long-term disease control may be the result of disease-modifying effects of chlormethine. Previous studies have shown targeted reductions in malignant T-cell clones in patients treated with chlormethine gel as well as improved post-treatment responses. Further research is needed to determine the effectiveness and safety of combination treatment regimens with chlormethine gel and to assess the impact chlormethine gel has on disease control.

Effect of recombinant human brain natriuretic peptide on efficacy, hemodynamics and NT-proBNP in elderly patients with heart failure.

To investigate the effects of recombinant human brain natriuretic peptide (rhBNP) on efficacy, hemodynamics, and N-terminal pro-brain natriuretic peptide (NT-proBNP) in elderly patients with heart failure (HF). In this retrospective analysis, the clinical data of 112 HF patients who visited the First Affiliated Hospital of Anhui University of Chinese Medicine between March 2019 and October 2022 were analyzed. On the basis of standard HF treatment, 52 patients additionally treated with milrinone intravenous were set as the control group (Con) and 60 patients with rhBNP were set as the observation group (Obs). The therapeutic efficacy and pre- and post-treatment echocardiographic indexes, NT-proBNP and hemodynamics were recorded and compared, and the adverse drug reactions and quality of life scores after treatment were counted. The Obs group showed a markedly higher post-treatment overall response rate than the Con (P=0.002). Besides, more obvious improvement of NT-proBNP and hemodynamic indexes were determined in the Obs group compared to the Con (P=0.000). Evidently ameliorated left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic diameter (LVESD) were observed in both groups after treatment, with more pronounced improvement in the Obs group (all P=0.000). The Obs group also exhibited an evidently lower incidence of adverse reactions and a better quality of life than the Con after treatment (P=0.000). rhBNP can effectively improve the cardiac function and hemodynamics in elderly HF patients, with high safety and few adverse reactions.

Surface engineered nanohybrids in plasmonic photothermal therapy for cancer: Regulatory and translational challenges.

Plasmonic materials as non-invasive and selective treatment strategies are gaining increasing attention in the healthcare sector due to their remarkable optical and electronic properties, where the interface between matter and light becomes enhanced and highly localized. Some attractive applications of plasmonic materials in healthcare include drug delivery to target specific tissues or cells, hence reducing the side effects of the drug and improving their efficacy; enhancing the contrast and resolution in bioimaging; and selectively heating and destroying the cancerous cells while parting the healthy cells. Despite such advancements in photothermal therapy for cancer treatment, some limitations are still challenging. These include poor photothermal conversion efficiency, heat resistance, less accumulation in the tumor microenvironment, poor biosafety of photothermal agents, damage to the surrounding healthy tissues, post-treatment inflammatory responses, etc. Even though the clinical application of photothermal therapy is primarily restricted due to poor tissue penetration of excitation light, enzyme therapy is hindered due to less therapeutic efficacy. Several multimodal strategies, including chemotherapy, radiotherapy, photodynamic therapy, and immunotherapy were developed to circumvent these side effects associated with plasmonic photothermal agents for effective mild-temperature photothermal therapy. It can be prophesied that the nanohybrid platform could pave the way for developing cutting-edge multifunctional precise nanomedicine via an ecologically sustainable approach towards cancer therapy. In the present review, we have highlighted the significant challenges of photothermal therapy from the laboratory to the clinical setting and their struggle to get approval from the Food and Drug Administration (FDA).

Evaluating real-world effectiveness of accelerated transcranial magnetic stimulation for treatment-resistant depression in a tertiary referral center based in Quebec, Canada

ObjectiveTo assess the effectiveness of accelerated transcranial magnetic stimulation (TMS) for treatment-resistant depression (TRD) in a tertiary referral center in Quebec, Canada, focusing on a real-world clinical setting. MethodsWe reviewed the data of 247 TRD patients treated between January 2012 and May 2022 who received accelerated TMS. Participants were adults diagnosed with unipolar or bipolar depression, resistant to at least two antidepressant trials, and assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). ResultsSignificant symptom reduction was found in the completer sample (N = 147), with 46.3 % of patients meeting post-treatment response criteria and 36.1 % achieving remission. Baseline severity of depression, age, and the number of antidepressant trials were key predictors of treatment outcomes. Patients who did not complete treatment had generally more severe depressive and anxious symptoms and greater treatment resistance. No significant differences in response rates were observed across different TMS coils. ConclusionThe study demonstrated the effectiveness and tolerability of accelerated TMS for TRD in a real-world clinical setting.

Low RNA disruption during neoadjuvant chemotherapy predicts pathologic complete response absence in patients with breast cancer.

In previously reported retrospective studies, high tumor RNA disruption during neoadjuvant chemotherapy predicted for post-treatment pathologic complete response (pCR) and improved disease-free survival at definitive surgery for primary early breast cancer. The BREVITY (Breast Cancer Response Evaluation for Individualized Therapy) prospective clinical trial (NCT03524430) seeks to validate these prior findings. Here we report training set (Phase I) findings, including determination of RNA disruption index (RDI) cut points for outcome prediction in the subsequent validation set (Phase II; 454 patients). In 80 patients of the training set, maximum tumor RDI values for biopsies obtained during neoadjuvant chemotherapy were significantly higher in pCR responders than in patients without pCR post-treatment (P = .008). Moreover, maximum tumor RDI values ≤3.7 during treatment predicted for a lack of pCR at surgery (negative predictive value = 93.3%). These findings support the prospect that on-treatment tumor RNA disruption assessments may effectively predict post-surgery outcome, possibly permitting treatment optimization.

Major impact of prognosis by age and sex in patients with primary mediastinal large B‑cell lymphoma.

The effective prognostic factors for primary mediastinal large B-cell lymphoma (PMLBCL) vary among published studies. The aim of the present study was to explore the factors influencing the overall survival (OS) and progression-free survival (PFS) of patients with PMLBCL at a single institute in Taiwan. This retrospective study was conducted to analyze the prognostic impact of age, sex, disease stage, International Prognostic Index (IPI) score, treatment modality and initial response. A total of 72 patients with a median age of 28 years were included in the study. The mean OS and PFS were 171.40 and 159.77 months, respectively. Female sex, age ≤60 years, receiving radiotherapy (RT) and achieving a complete response were found to be associated with a significantly improved OS and PFS. In addition, high-intensity chemotherapy and an IPI score ≤1 were associated with longer OS, and early-stage disease was associated with a PFS superior to that of advanced-stage disease. The predictive value of IPI is limited in PMLBCL. Therefore, it is necessary to develop a novel prognostic system. The present study revealed the impact of sex on prognosis and, therefore, this factor should be considered in future prognostic evaluations. Since a complete post-treatment response was found to be important, high-intensity chemotherapy is recommended. However, low-intensity treatment followed by RT consolidation appears to be a feasible approach in elderly patients.

Characteristics of Patients with Subjective Sleep Problems after Cognitive Behavioral Therapy for Insomnia: Secondary Analyses of a Randomized Controlled Trial.

Objective Cognitive behavioral therapy for insomnia (CBT-I) is the first-line treatment for insomnia, but half of the patients do not reach remission. This study aimed to explore subjective remission by investigating the characteristics of patients who reported lingering sleep problems after CBT-I. Methods Secondary analyses of a randomized controlled trial of group CBT-I in 72 primary care patients with insomnia disorder. Sociodemographic characteristics and outcomes (insomnia severity, sleep variables, hypnotics use, fatigue, depressive symptoms, and dysfunctional beliefs/attitudes), including baseline data and symptom change, were investigated in relation to patients' posttreatment response to the yes-or-no question "Would you say that you have sleep problems?" Results A total of 56.9% of patients reported sleep problems after CBT-I. At baseline, they had worse depressive symptoms (14.9 (SD 7.5) vs. 10.2 (SD 5.9), p = 0.006) and more awakenings (2.6 (SD 1.5) vs. 1.8 (SD 1.3), p = 0.034) than those in subjective remission from sleep problems. Patients in the non-remission and remission groups showed similar improvements in sleep, fatigue, and depressive symptoms, but patients in the non-remission group had improved less in insomnia severity, dysfunctional beliefs/attitudes about sleep, and hypnotic use. In patients with more pronounced depressive symptoms before CBT-I, change in depressive symptoms during treatment partially explained subjective remission from sleep problems. Discussion More severe depressive symptoms prior to CBT-I and less improvements in depressive symptoms during treatment predicted remaining subjective sleep problems after treatment. These findings highlight the importance of assessing depressive symptoms in primary care patients with insomnia, as patients with pronounced depressive symptoms may need tailored treatment.

Manual and Semi-Automated Measurement and Calculation of Osteosarcoma Treatment Effect Using Whole Slide Image and Qupath.

In osteosarcoma, the most significant indicator of prognosis is the histologic changes related to tumor response to preoperative chemotherapy, such as necrosis. We have developed a method to measure the osteosarcoma treatment effect using whole slide image (WSI) with an open-source digital image analytical software Qupath. In Qupath, each osteosarcoma case was treated as a project. All H&E slides from the entire representative slice of osteosarcoma were scanned into WSIs and imported into a project in Qupath. The regions of tumor and tumor necrosis were annotated, and their areas were measured in Qupath. In order to measure the osteosarcoma treatment effect, we needed to calculate the percentage of total necrosis area over total tumor area. We developed a tool that can automatically extract all values of tumor and necrosis areas from a Qupath project into an Excel file, sum these values for necrosis and whole tumor respectively, and calculate necrosis/tumor percentage. Our method that combines WSI with Qupath can provide an objective measurement to facilitate pathologist's assessment of osteosarcoma response to treatment. The proposed approach can also be used for other types of tumors that have clinical need for post-treatment response assessment.

Abstract 15033: Development of an Interpretable Machine Learning Model for Predicting Individual Response to Antihypertensive Treatments

Introduction: Accurate prediction of individual response to anti-hypertensive treatment is crucial in enhancing the safety and efficiency of offering appropriate regimens to attain desired blood pressure (BP) goals. Hypothesis: Machine learning (ML) based models could accurately predict the BP reduction of different antihypertensive regimens. Methods: We utilized data from the LIGHT study, a pragmatic, cluster-randomized trial conducted in 94 primary care institutions in China, involving 13146 visits of 5192 patients who were required to attend the clinic for hypertension management every 3 months during an overall study period of 1 year. Clinical and laboratory variables, baseline BP, and anti-hypertensive therapies at baseline and at follow-up were used to develop models for predicting post-treatment individual BP response. Five ML algorithms were applied as candidate models, and mean squared error (MSE) was used to evaluate the model performance ( panel A ). Results: The mean (standard deviation) age of the study population at baseline was 64.2 (14.0) years, and 2207 (42.5%) were female. 29 features selected by the least absolute shrinkage and selection operator method and purposeful selection were used to build the model, including age, sex, weight, waist circumference, BMI, baseline systolic and diastolic BP, smoking status, visit interval, history of coronary heart disease, diabetes, and dyslipidemia, and baseline and prescript antihypertensive drugs. Among all candidate models, the Catboost model had the best performance with a training MSE of 149.6 and a validation MSE of 135.2 ( panel B ). The most important features include baseline BP, age, weight, and BMI ( panel C and D ). Conclusions: We developed an ML-based model for predicting the response to antihypertensive regimens for assisting clinicians to achieve individualized antihypertensive treatment effectively and safely.

Painless photodynamic therapy for facial actinic keratoses: A retrospective cohort study of the post-treatment inflammatory response

IntroductionPhotodynamic therapy (PDT) is a safe, non-mutagenic, and non-scarring treatment for actinic keratoses (AK). Background‘Painless’ photodynamic therapy (p-PDT) is a regimen for AK that employs simultaneous aminolevulinate incubation and blue light illumination. The efficacy of p-PDT resembles that of traditional PDT, but detailed mechanisms of action for p-PDT are not well understood. MethodsTo characterize the inflammatory effects of the p-PDT procedure 48 h following treatment and determine the association of inflammation with precancer burden, we performed a retrospective cohort study of 104 patients with AK of face or scalp treated with p-PDT between 2017 and 2019. Patients self-reported their side effects 48 h following p-PDT and took photographs of their face and scalp. Photographs were edited to define seven anatomic regions, and erythema was scored by four investigators. ResultsNinety-eight patients provided photographs suitable for erythema evaluation. Most patients experienced 2 or more side effects and some pain 48 h post-procedure. Females experienced more pain (p = 0.01) and side effects (p = 0.002) compared to males. AK burden was positively associated with post p-PDT erythema response (p < 0.0001) at all sites, but particularly in the temples (p = 0.002) and supralabial area (p = 0.009). DiscussionThis study confirms a strong clinical inflammatory response after p-PDT. Severity of inflammation is positively associated with AK tumor burden, suggesting that post-treatment inflammation may be a pre-requisite for p-PDT efficacy. Interestingly, the results also identify certain gender-related differences in the severity of side effects experienced by patients post-PDT.

EPRO Use in Men Receiving Radiotherapy for Localized Prostate Cancer

Describe real-time reporting of localized prostate cancer and patient-reported cancer/radiation treatment symptoms via mobile app or computer-based system. Patients (n = 177) who received standard-of-care treatment at an academic specialty care hospital in Finland from Jan. 2015 through Dec. 2020 and used a proprietary ePRO tool at least once during their course of radiotherapy were included in this study. The Clinical Care Team (CCT) utilized bidirectional software to administer an electronic questionnaire that included CTCAE (v5) items to report disease and/or treatment symptoms at least once during treatment and at 1 month and 3 months posttreatment. Patients could also complete the questionnaire ad hoc. The questionnaire is enhanced with programmed "emergency" and "urgent" clinical alerts which are used for two purposes: sending pre-programmed recommendations to patients and triaging patients by symptom severity on the CCT's dashboard in order to facilitate patient follow-up. Data were analyzed descriptively. Patients tended to be older (M = 73.16 years, SD = 6.86) and lived outside the city (n = 119, 67.23%). The average course of radiation treatment was over one month in duration (M = 39.21 days, SD = 16.96); relatively few patients received surgery (n = 21, 6.78%) and/or hormone therapy (n = 20, 11.30%). Almost all patients completed the module during treatment (response rate = 92.09%) and at posttreatment (response rate = 94.92%). Ad hoc reports were submitted by 18.07% of patients during treatment (78 submissions) and 28.24% of patients posttreatment (182 submissions). The most frequently reported symptoms during and after treatment were urination-related (during treatment = 73.44%; post treatment = 60.45%), diarrhea/constipation (during treatment = 50.84%; post treatment = 31.63%), and sexual function (during treatment = 44.63%; post treatment = 57.06%). Systematizing real-time collection of patient-reported symptoms is increasingly acknowledged as an adjunct to improving patient experience. The high usage observed in this study is a behavioral indicator that ePRO use is accepted and valued by patients. Perhaps the most interesting finding is the use of the ad hoc reporting function. During radiotherapy, patients have almost daily access to the CCT and can easily communicate symptoms; nevertheless, they still used the ePRO platform to report cancer/treatment effects. Understandably, in the posttreatment period, where scheduled contact with the CCT is less frequent, ad hoc usage was higher. These findings suggest that ePRO use (scheduled and ad hoc) helps address an unmet need and has the potential to empower patients throughout their cancer journey.

From planned neck dissection to PET response to circulating tumour DNA: changes in post-treatment assessment of HPV-driven oropharyngeal cancer†.

Circulating tumour human papillomavirus DNA (ctHPVDNA) is an emerging tool to assess post-treatment response in patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC). Its use is not a standard practice, however, with interval F-18 FDG PET/CT and fiberoptic examination preferred. Post-treatment PET/CT at 3 months has a low positive predictive value (PPV), especially in patients with HPV+ OPSCC treated with (chemo)radiation therapy (CRT). We aimed to compare 3-6 month post-treatment PET/CT and ctHPVDNA test results to determine the most effective option for post-treatment response assessment. Patients with HPV+ OPSCC that underwent commercially available ctHPVDNA blood testing after curative intent treatment were identified. Demographic, clinical, treatment, surveillance and oncologic outcome information were collected for each patient. Specificity and false positive rate were calculated for post-treatment PET/CT and ctHPVDNA. 80% of patients had Stage I disease. 52% of the population was treated with definitive chemoradiation (43%) or accelerated radiation (9%), with the remaining patients treated with transoral robotic surgery (TORS) +/- risk-adapted adjuvant therapy. In total, 25 patients underwent ctHPVDNA testing and PET/CT at 3-6 months after finishing treatment. At 3-6 months post-treatment, specificity of ctHPVDNA and PET/CT was 96% and 56%, correlating to false positive rates of 4% and 44%, respectively. ctHPVDNA is more reliable than PET/CT following treatment in patients with HPV+ OPSCC, and its incorporation in post-treatment response assessment will decrease the rate of anxiety over persistent disease and lead to a decrease in unnecessary medical procedures, including completion of neck dissection.

Managing Expectations from Intensively Monitored Watershed Studies

AbstractIntensively monitored watershed (IMW) studies, the intent of which is to quantify habitat restoration effects on salmonid populations, have been underway in the Pacific Northwest, USA, for more than two decades. Lack of population‐level response to habitat improvements by target species in some IMWs may be related to incomplete knowledge of factors regulating fish abundance, excessively prolonged restoration application periods, underappreciation of natural environmental and population variability, failure to carry out restoration at a sufficiently large scale within a watershed, lack of sufficient time to document a posttreatment response, or an actual failure of the restoration activities in those locations to achieve population recovery objectives. However, knowledge gained from IMWs has yielded important insight into (1) the long‐term responses of salmon and steelhead Oncorhynchus mykiss to different types of restoration and (2) the importance of placing freshwater habitat improvements in the context of changes in anadromous salmonid survival and growth during other life history stages. Scientists, funding organizations, and policymakers should appreciate the potential value of IMWs as long‐term barometers of the status of salmon populations and their habitats in watersheds where restoration activities are occurring. This requires a commitment to prolonged monitoring and an acknowledgment that environmental recovery after habitat restoration may take decades.

Early post-treatment MRI predicts long-term hepatocellular carcinoma response to radiation segmentectomy

ObjectivesRadiation segmentectomy using yttrium-90 plays an emerging role in the management of early-stage HCC. However, the value of early post-treatment MRI for response assessment is uncertain. We assessed the value of response criteria obtained early after radiation segmentectomy in predicting long-term response in patients with HCC.Materials and methodsPatients with HCC who underwent contrast-enhanced MRI before, early, and 12 months after radiation segmentectomy were included in this retrospective single-center study. Three independent radiologists reviewed images at baseline and 1st follow-up after radiation segmentectomy and assessed lesion-based response according to mRECIST, LI-RADS treatment response algorithm (TRA), and image subtraction. The endpoint was response at 12 months based on consensus readout of two separate radiologists. Diagnostic accuracy for predicting complete response (CR) at 12 months based on the 1st post-treatment MRI was calculated.ResultsEighty patients (M/F 60/20, mean age 67.7 years) with 80 HCCs were assessed (median size baseline, 1.8 cm [IQR, 1.4–2.9 cm]). At 12 months, 74 patients were classified as CR (92.5%), 5 as partial response (6.3%), and 1 as progressive disease (1.2%). Diagnostic accuracy for predicting CR was fair to good for all readers with excellent positive predictive value (PPV): mRECIST (range between 3 readers, accuracy: 0.763–0.825, PPV: 0.966–1), LI-RADS TRA (accuracy: 0.700–0.825, PPV: 0.983–1), and subtraction (accuracy: 0.775–0.825, PPV: 0.967–1), with no difference in accuracy between criteria (p range 0.053 to > 0.9).ConclusionmRECIST, LI-RADS TRA, and subtraction obtained on early post-treatment MRI show similar performance for predicting long-term response in patients with HCC treated with radiation segmentectomy.Clinical relevance statementResponse assessment extracted from early post-treatment MRI after radiation segmentectomy predicts complete response in patients with HCC with high PPV (≥ 0.96).Key Points• Early post-treatment response assessment on MRI predicts response in patients with HCC treated with radiation segmentectomy with fair to good accuracy and excellent positive predictive value.• There was no difference in diagnostic accuracy between mRECIST, LI-RADS, and subtraction for predicting HCC response to radiation segmentectomy.

Investigation of response factors for monotherapy with immune checkpoint inhibitors in non-small cell lung cancer patients with PD-L1 expression

Immune checkpoint inhibitor (ICI) monotherapy is currently approved for the treatment of advanced non-small cell lung cancer (NSCLC) patients with programmed death ligand-1 (PD-L1) expression ≥50%. However, the efficacy of ICI monotherapy in patients with PD-L1 expression <50% has not yet been fully elucidated. The aim of this study was to identify the clinical characteristics of NSCLC patients with PD-L1 expression <50% who respond to single-agent ICIs and factors that predict response. Patients with advanced or recurrent NSCLC with a PD-L1 tumor proportion score (TPS) of 50% or less who received new monotherapy with an ICI between July 2012 and December 2022 were retrospectively analyzed. Patients with response were compared with those without response in the post-treatment response assessment. Among the 37 patients, six (16.2%) NSCLC patients in the response group responded to ICI monotherapy and had a significantly lower body mass index (BMI) (p = 0.003). Significantly more patients in the response group developed immune-related adverse events (irAEs) than in the nonresponse group (p < 0.001). Multivariate analysis identified high BMI as a significant independent risk factor predicting nonresponse to ICI monotherapy in NSCLC patients with PD-L1 < 50%. Among NSCLC patients with PD-L1 < 50%, those with a higher BMI were more likely to be nonresponders to ICI monotherapy. In addition, the group that responded to ICI monotherapy may have been at higher risk of developing irAEs, suggesting that careful follow-up is warranted.

Identifying correlates of post treatment responses for unresectable locally advanced non-small cell lung cancer (LA NSCLC).

149 Background: Curative treatment for unresectable LA NSCLC comprises chemoradiotherapy (CRT) and immunotherapy (IO). However, this uniform approach does not take into account the intrinsic heterogeneity of NSCLC and nearly half of all pts relapse within the first year. This highlights the need to define distinct molecular and phenotypic subgroups of LA NSCLC so that we can interrogate the divergent responses to CRT-IO and identify biomarkers that can guide pt specific strategies. Methods: Consecutive pts treated with CRT +/- IO from May 2010 and recruited to an observational study were retrospectively analysed (N = 336). All pts with adenocarcinoma (ADC) were subject to reflex molecular profiling including NGS and FISH testing for ALK, ROS1, MET and RET. Of note, tracking of bespoke circulating tumour DNA (ctDNA) levels was performed for 25 pts. Plasma samples were collected at longitudinal timepoints pre, during and post CRT (N = 118; median 5 samples/ pt). WES of biopsies and matched normal DNA was used to design tumour informed ctDNA assays to track 16 single nucleotide variants in plasma samples. ctDNA levels were then quantified as mean tumour molecule per mL (MTM/mL). Primary endpoint was progression free survival (PFS). Results: Median age was 61 (IQR 48, 74). Of 336 pts, 74% were male; 32% never smokers; 54% were ADC, 33% squamous cell carcinoma (SCC); 18% had EGFR mutations (EGFRm), 37%EGFR wild type (EGFRw), 40% unknown EGFR status (EGFRu), 5% ALK rearranged, 1% ROS1 rearranged. At median follow-up of 44 months (m), median PFS for the entire cohort was 16.2m. Pts who received consolidation IO had longer PFS [IO, not reached vs no IO, 14.9m; P = 0.05]. Median PFS was shorter for pts with EGFRm [EGFRm, 13m vs EGFRw, 22.5m vs EGFRu, 15.8m]. Patterns of failure were analysed according to local in-field, regional out-field and distant. EGFRm pts were less likely to fail locally in-field [EGFRm, 12% vs EGFRw,18% vs EGFRu, 28%] and significantly more likely to develop distant metastases as first site of failure post CRT [EGFRm, 51% vs EGFRw, 28% vs EGFRu, 19%; P = 0.01]. For the 25 pts with ctDNA analysed, 24 pts had evaluable ctDNA post CRT. Significant heterogeneity was noted at baseline pre CRT [EGFRm, 6.45 vs EGFRw, 7.49 vs SCC, 37.67 MTM/mL; P = 0.05]. No difference was noted in PFS between pts with high vs low baseline ctDNA. Of note, 14 of 24 (58%) pts achieved undetectable ctDNA post CRT and had significantly longer PFS [undetectable, 24.1m vs detectable, 3.5m; P = 0.02]. Conclusions: Here, we demonstrate distinct phenotypic responses to CRT based on molecular subtypes of NSCLC. Crucially, we demonstrate clinical feasibility of deploying tumour-informed ctDNA assays in LA NSCLC with detection of ctDNA post CRT serving as a potential actionable biomarker to guide intensification strategies, providing a window into developing patient-specific combinatorial approaches.

Prediction of lymphoma response to CAR T cells by deep learning-based image analysis.

Clinical prognostic scoring systems have limited utility for predicting treatment outcomes in lymphomas. We therefore tested the feasibility of a deep-learning (DL)-based image analysis methodology on pre-treatment diagnostic computed tomography (dCT), low-dose CT (lCT), and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images and rule-based reasoning to predict treatment response to chimeric antigen receptor (CAR) T-cell therapy in B-cell lymphomas. Pre-treatment images of 770 lymph node lesions from 39 adult patients with B-cell lymphomas treated with CD19-directed CAR T-cells were analyzed. Transfer learning using a pre-trained neural network model, then retrained for a specific task, was used to predict lesion-level treatment responses from separate dCT, lCT, and FDG-PET images. Patient-level response analysis was performed by applying rule-based reasoning to lesion-level prediction results. Patient-level response prediction was also compared to prediction based on the international prognostic index (IPI) for diffuse large B-cell lymphoma. The average accuracy of lesion-level response prediction based on single whole dCT slice-based input was 0.82+0.05 with sensitivity 0.87+0.07, specificity 0.77+0.12, and AUC 0.91+0.03. Patient-level response prediction from dCT, using the "Majority 60%" rule, had accuracy 0.81, sensitivity 0.75, and specificity 0.88 using 12-month post-treatment patient response as the reference standard and outperformed response prediction based on IPI risk factors (accuracy 0.54, sensitivity 0.38, and specificity 0.61 (p = 0.046)). Prediction of treatment outcome in B-cell lymphomas from pre-treatment medical images using DL-based image analysis and rule-based reasoning is feasible. This approach can potentially provide clinically useful prognostic information for decision-making in advance of initiating CAR T-cell therapy.

Methodologies for task-fMRI based prognostic biomarkers in response to aphasia treatment

With the diversity in aphasia coupled with diminished gains at the chronic phase, it is imperative to deliver effective rehabilitation plans. Treatment outcomes have therefore been predicted using lesion-to-symptom mapping, but this method lacks holistic functional information about the language-network. This study, therefore, aims to develop whole-brain task-fMRI multivariate analysis to neurobiologically inspect lesion impacts on the language-network and predict behavioral outcomes in persons with aphasia (PWA) undergoing language therapy. In 14 chronic PWA, semantic fluency task-fMRI and behavioral measures were collected to develop prediction methodologies for post-treatment outcomes. Then, a recently developed imaging-based multivariate method to predict behavior (i.e., LESYMAP) was optimized to intake whole-brain task-fMRI data, and systematically tested for reliability with mass univariate methods. We also accounted for lesion size in both methods. Results showed that both mass univariate and multivariate methods identified unique biomarkers for semantic fluency improvements from baseline to 2-weeks post-treatment. Additionally, both methods demonstrated reliable spatial overlap in task-specific areas including the right middle frontal gyrus when identifying biomarkers of language discourse. Thus whole-brain task-fMRI multivariate analysis has the potential to identify functionally meaningful prognostic biomarkers even for relatively small sample sizes. In sum, our task-fMRI based multivariate approach holistically estimates post-treatment response for both word and sentence production and may serve as a complementary tool to mass univariate analysis in developing brain-behavior relationships for improved personalization of aphasia rehabilitation regimens.

DS03 Lentigo maligna: is it time to put down the scalpel?

Abstract Lentigo maligna (LM) is a subtype of melanoma in situ that often proves to be a diagnostic and therapeutic challenge. Treatment aims to prevent progression to an invasive tumour called lentigo maligna melanoma (LMM). In the UK, common treatment modalities include conventional excision, staged re-excisions, slow Mohs surgery or expectant monitoring. Although considered the ‘gold standard’, surgical excision of LM can be disfiguring as it frequently affects cosmetically sensitive areas requiring complex surgical reconstructions. Topical imiquimod 5% presents a pragmatic alternative treatment modality without the need for surgery. In vivo reflectance confocal microscopy (RCM) allows real-time noninvasive delineation of LM. Evidence suggests this is an effective diagnostic tool for pre- and post-treatment evaluation (Brand FL, Jafari SM, Hunger RE. Confocal microscopy and lentigo maligna: an in vivo pilot study for the assessment of response to imiquimod therapy. Dermatology 2019; 235:150–5). We retrospectively analysed 35 cases of histologically confirmed LM that completed treatment with imiquimod between 2018 and 2022. The average patient age at diagnosis was 73.9 years, with a female : male ratio of 18 : 17. Following assessment with RCM, patients were prescribed a protocol of topical imiquimod 5% once a day, 5 days per week for 12 weeks, along with instructions to apply this 10 mm beyond the mapped area or a cosmetic unit (Australia and New Zealand Melanoma Trials Group RADICAL trial). Patients were counselled about expected side-effects; all completed the course and achieved significant inflammation and superficial ulceration. To ensure a response was achieved, the following stepwise interventions were used: application increased to 7 days per week, occlusion with a dressing and addition of a topical retinoid. Repeat RCM was performed 6 months after treatment completion. At this point, 30 of 35 (86%) patients responded with no evidence of residual LM on RCM. Three cases required a second course of treatment. Two of these were shown to be clear on RCM, while the third is clinically clear and awaiting RCM confirmation. A fourth patient was lost to follow-up. A further patient has failed two courses and is about to embark on a third round of treatment. In total, 16 cases completed the 12-month review and maintained clearance. We demonstrate that imiquimod is an effective treatment for LM, potentially avoiding extensive surgery and complex reconstruction. Reflectance confocal microscopy can be used to delineate the extent of the LM and assess the post-treatment response. Our preliminary data suggest a significant proportion of LM cases achieved clearance with no recurrences to date. Follow-up of these patients will help evaluate the long-term efficacy of imiquimod, but our data suggest this treatment protocol provides a promising alternative to surgical intervention.