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Radiation-induced lymphopenia is gaining prominence due to implications in cancer survivorship. No consensus is established regarding lymph node irradiation (LNI) and the optimal treatment strategy in prostate cancer (definitive radiotherapy (dRT) vs radical prostatectomy with possible following post-operative radiotherapy (poRT)). Herein we assess the impact of LNI and radiotherapy (RT) strategies on lymphopenia, trying to fill a gap in existing research. In this retrospective cohort study, we analyzed data from patients who received definitive radiotherapy (dRT) or post-operative radiotherapy (poRT) with or without LNI for localized prostate adenocarcinoma (stages T1-T4N0-1M0) at our tertiary cancer center in 2021.We retrieved complete blood count (CBC) of all eligible patients from the initiation of RT to January 2024. The primary endpoint was to compare depth of lymphocyte nadir between different treatment groups: 1) RT with LNI vs RT without LNI and 2) dRT vs poRT. Secondarily, we assessed the time of nadir occurrence and the time taken for recovery from nadir. We developed a generalized additive model (GAM) using LOESS for absolute lymphocyte count (ALC). U-Mann-Whitney test was used for intergroup comparison. Analyses were performed in R (version 4.2.3). One thousand nine hundred one CBC of 263 patients have been analyzed. Lymphopenia CTCAE ≥G2 occurred in 124 (47.1%) and ≥G3 in 50 patients (19%) and was not correlated with age or RT duration. The ALC nadirs differs (p < 0.001) between the RT with LNI group (median = 0.51x10³ cells/µL) and the RT without LNI group (median = 1.01x10³ cells/µL). No similar differences were seen between different treatment strategies groups (dRT vs poRT). Our GAM (R2 = 0.200) indicated that ALC nadir should be expected on the 75th, 75th, and 64th day from initiation of RT for the overall cohort, those with RT with LNI, and those with RT without LNI, respectively. Recovery from nadir is anticipated on the 142nd, 142nd and 113th day from initiation of RT, for the overall cohort, those with RT with LNI, and those with RT without LNI, respectively. Lymphopenia is induced by lymph node irradiation and occurs typically in third month after start of radiotherapy. Our results shed new light on the discussion regarding lymph node irradiation strategies in prostate cancer. [ABSTRACT FROM AUTHOR]

New approaches are needed for frail or elderly patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC) who are unfit to receive cisplatin with concurrent radiotherapy (RT). NBTXR3 is a first-in-class radioenhancer, composed of functionalized hafnium oxide nanoparticles, administered by a single intratumoral injection and activated by RT. NBTXR3 locally amplifies the anti-tumoral response of RT without adding toxicity to surrounding healthy tissue as shown in a randomized trial in soft tissue sarcoma. This two-part study: dose-escalation followed by the dose-expansion part reported here, evaluated the safety and preliminary efficacy for NBTXR3 activated by RT in elderly or frail patients ineligible to cisplatin. Patients with previously untreated AJCC 8th Stage III-IVA or T3,T4 SCC of the oral cavity or oropharynx (OPC) ineligible to cisplatin were enrolled. Eligible patients received a single IT injection of NBTXR3 at the recommended dose (22% of the baseline tumor volume) followed by RT (IMRT 70 Gy in 35 fractions). The primary objectives of the dose expansion part were to test the recommended dose, to confirm its safety, and obtain preliminary evidence of efficacy. The secondary objectives included the evaluation of progression-free survival (PFS) and overall survival (OS). 56 patients in the dose expansion part were treated from April 2019-January 2022; 44 patients were evaluable for objective tumor response. In the all treated (AT) population, median age was 72 years. 67% had age-adjusted Charlson Comorbidity Index scores ≥4, 55.4% had OPC (45.2% HPV+) and 80% had T3-4. Median injected volume of NBTXR3 was 13.6 [0.6-57.1] mL. Grade ≥ 3 treatment emergent adverse events (TEAE) reported as potentially related to NBTXR3 or to injection procedure were 1.3% all TEAEs reported, respectively. In the evaluable (EV) population, ORR of the NBTXR3 injected lesion was 81.8%; complete response rate was 63.6%. ORR of injected and non-injected lesions was 79.5%. Median PFS by independent central review was 11.4 mos (AT) and 16.9 mos (EV). Median OS was 18.1 mos (AT) and 23.1 mos (EV). PFS of injected lesion (LPFS) was 16.9 mos (AT) and not reached (EV). Exploratory analyses of additional endpoints will be presented. NBTXR3 IT injection followed by activation with RT was confirmed to be feasible and well tolerated in elderly or frail patients with LA HNSSC and significant comorbidities. The high ORR suggests that NBTXR3+RT is effective in this elderly population ineligible to cisplatin with a high unmet medical need. These results reinforced by exploratory analyses support our ongoing phase III study comparing NBTXR3/RT±cetuximab vs. RT±cetuximab in platinum-based chemotherapy ineligible elderly patients with LA-HNSCC: NANORAY 312 (NCIT04892173). [ABSTRACT FROM AUTHOR]

As shown in RAPIDO and PRODIGE-23 trials, total neoadjuvant therapy for rectal cancer increases the complete response rate, however, the overall survival benefit remains uncertain. Although postponing surgery assures more time for tumor downstaging, it also increases surgical complications and can worsen prognosis in non-responding tumors. We aimed to develop a clinical and radiomics-based model for early treatment failure (ETF) prediction after neoadjuvant radiochemotherapy (RCHTx) for rectal cancer. We conducted a prospective cohort analysis of 92 consecutive and eligible patients with rectal adenocarcinoma treated with neoadjuvant radiochemotherapy in the years 2018-2020, and followed until February 2022. We defined ETF as postoperative poor pathological response and no MRI-confirmed downstaging; or unresectability after neoadjuvant treatment; or cancer-related or treatment-related death within 18 months since treatment initiation. Collected clinical data included physical examination, grading, staging (before and after RCHTx), biomarker levels, RCHTx prescription details, and pre-operative MRI tumor and nodal characteristics. Radiomic features were extracted from GTV delineated on axial MRI T2 TSE sequences. To develop a predictive model, we followed OmicSelector-based (https://biostat.umed.pl/OmicSelector) feature selection, logistic regression (LR), and artificial deep neural network model development procedure. After splitting into training (60%), testing (20%), and validation (20%) datasets, the final feature set was selected based on the highest average logistic regression accuracy on all sets, while all patients with MRI performed outside our institution were included in the testing set (compensating possible batch effect). ETF was experienced by 24% of patients and was associated with significantly shorter overall survival (median 12.1 months [95%CI:8.5-16.5] vs. not reached, p<0.0001). None of the clinical factors was significantly associated with ETF (adjusted p value>0.05; AUC ROC range 0.39-0.64). LR model based on clinical factors presented overfitting (accuracy 82% on the training set, 56.2% on testing and 68.8% on validation set). The best feature set included 14 selected radiomic features, patient's weight, T-stage, grading, mesorectal fascia and nodal involvement. LR model based on those features achieved perfect accuracy on training and testing sets and 81.3% accuracy on the validation set. Deep neural network model utilizing selected clinical and radiomic features achieved 87.5% accuracy (80% sensitivity, 91% specificity) on testing and 93.8% accuracy (100% sensitivity, 91% specificity) on validation set. Combined clinical and radiomics-based deep learning model could predict ETF after RCHTx for rectal cancer with at least 80% sensitivity and 90% specificity. Prediction of ETF after RCHTx could select high-risk patients who may require non-standard treatment. [ABSTRACT FROM AUTHOR]