Mayuri Charnalia

RECIST 1.1 versus clinico-radiological response assessment for locally advanced cervical cancer: implications on interpreting survival outcomes of future trials

To investigate differences in standard clinico-radiological evaluation versus Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for reporting survival outcomes in patients with locally advanced cervical cancer treated with chemoradiation and brachytherapy. Between November 2017 and March 2020, patients recruited in cervical cancer trials were identified. MRI at diagnosis and at least one follow-up imaging was mandatory. Disease-free survival and progression-free survival were determined using standard evaluation (clinical examination and symptom-directed imaging) and RECIST 1.1. Agreement between criteria was estimated using κ value. Sensitivity analysis was done to test the sensitivity, specificity, and accuracy of RECIST 1.1 in detecting response to treatment. Sixty-nine eligible patients had at least one target lesion. Thirty-three patients (47.8%) had pathological lymph nodes. Of these 33 patients, RECIST 1.1 classified only 18% (6/33) as 'target nodal lesions' and the remaining nodes as 'non-target'. There were 6 (8.7%) and 8 (11.6%) patients with disease events using RECIST 1.1 and standard evaluation, respectively. The disease-free survival at 12, 18, and 24 months using RECIST 1.1 was 94.2%, 91.2%, 91.2%, and with standard evaluation was 94.2%, 89.7%, and 88.2%, respectively (p=0.58). Whereas, progression-free survival at 12, 18, and 24 months using RECIST 1.1 and standard evaluation were same (94.2%, 91.2%, and 91.2%, respectively). The κ value was 0.84, showing strong agreement in assessing disease-free survival, although an absolute difference of 3% between endpoint assessment methodologies. RECIST 1.1 had a sensitivity of 75% (95% CI 34.91% to 96.81%), specificity of 100% (95% CI 94.13% to 100%), and accuracy of 97.1% (95% CI 89.92% to 99.65%). The study showed 1.5% and 3% difference in disease-free survival at 18 and 24 months and no difference in progression-free survival between RECIST 1.1 and standard evaluation in a patient cohort with low event rate.

Gynaecological reirradiation with image-guided radiotherapy: Tumour Control Probability and Normal Tissue Complication Probability in pre-immunotherapy era

Management of recurrent gynaecological cancers after previous pelvic radiation is challenging. This institutional cohort describes clinical outcomes with image-guided radiotherapy techniques. From 2020 to 2023, patients with recurrent or second primary gynaecological malignancies previously treated with radiotherapy were included. Reirradiation was delivered using image-guided volumetric arc therapy (IG-VMAT), stereotactic body radiotherapy (SBRT), and/or image-guided brachytherapy (IGBT) as clinically appropriate. Infield control, progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Prognostic factors for infield control were assessed with uni- and multivariate analyses. Adverse events were reported (CTCAE version 5.0). The dose-response effect for tumour control and late effects were estimated. Seventy patients underwent reirradiation. Of these 62 (88.5 %), 6 (8.5 %), and 2 (2.8 %) had cervical cancer, endometrial cancer, and vulvovaginal cancer, respectively. The majority of patients had squamous cell histology (81.4 %). Fifty-nine patients (84.2 %) were treated for local and/ or nodal recurrence, and 11 patients were treated (15.8 %) for second primary cancer. The median reirradiation dose was 50 Gy (IQR 42.2-64.2 Gy). In this cohort, 34/70 (48.6 %) patients received systemic chemotherapy, and no Bevacizumab or Immunotherapy. With a median follow-up of 37 months, the 3-year infield control, PFS, and OS were 63.5 %, 62.4 %, and 68 %, respectively. Reirradiation dose ≥50 Gy and disease-free interval ≥24 months were independently associated with improved infield control (p = 0.04, 0.004). Grade ≥3 gastrointestinal/genitourinary toxicity occurred in 18.5 % patients. Cumulative EQD2 ≥130 Gy Image-guided radiotherapy techniques for reirradiation achieve excellent local control with acceptable toxicity in patients with recurrent gynaecological cancers.