Radiation boost for synchronous solitary inguinal lymph node metastasis during neoadjuvant chemoradiotherapy for locally advanced rectal cancer

Background Some patients with locally advanced rectal cancer (LARC) present with inguinal lymph node metastases without evidence of other systemic disease, known as solitary inguinal lymph node metastasis (SILNM). These patients may represent a distinct subset who have a more favorable prognosis and should be treated with curative intent. The optimal treatment strategy for these patients has not been determined. Methods We retrospectively reviewed 16 consecutive LARC patients diagnosed between January 2017 and December 2019, who had SILNM, were treated with an inguinal lymph nodes (ILN) radiation boost with curative intent during neoadjuvant chemoradiotherapy (nCRT) and underwent total mesorectal excision (TME). We used Kaplan–Meier survival curves to calculate survival rates, and recorded radiation-related toxicity. Results None of these 16 patients developed pelvic or inguinal recurrences, and 3 of the patients developed distant metastases. The 3-year overall survival rate and locoregional relapse-free survival rate were both 100%. The 3-year disease-free rate and distant metastasis-free survival rate were both 81.3%. Of 5 patients who had ILN dissection for suspicious ILNs after neoadjuvant treatment, 2 had residual nodal tumor confirmed. Grade 3 toxicity was found in 5 patients, and no patients had lymphedema or other grade 4 or 5 toxicities. Conclusions In LARC patients with synchronous SILNM, a radiation boost to the ILNs during nCRT achieved excellent local control with acceptable toxicity. Though the optimal treatment strategy remains unclear, nCRT with an ILN radiation boost prior to TME may be a reasonable therapeutic approach to consider for this subset of patients.

QOL-20. IMPACT OF RADIATION DOSE AND VOLUME ON MEMORY FUNCTIONING IN CHILDREN WITH MEDULLOBLASTOMA: A REPORT FROM CHILDREN’S ONCOLOGY GROUP (COG) ACNS0331

BACKGROUND/OBJECTIVES We examined longitudinal verbal and visual memory functioning in children treated for medulloblastoma on COG protocol ACNS0331. METHODS Children with medulloblastoma participated in neuropsychological testing at three timepoints over a 6-year period. Children aged 3–7 years were randomized to receive craniospinal irradiation (CSI) of either 23.4Gy (standard dose; SDCSI) or 18Gy (lower dose; LDCSI). Children aged 8+ received SDCSI. All children were also randomized to receive either a reduced radiation boost to the involved field (IFRT) or a standard boost to the whole posterior fossa (PFRT). Memory functioning was evaluated an average of 0.67(T1), 2.95(T2), and 4.90(T3) years post-diagnosis. RESULTS Of 464 eligible patients enrolled on ACNS0331, 354 (76%; 65.3% male, 83.1% white) completed some neuropsychological testing. Mean age at diagnosis was 9.1 years (range=3–19). Verbal and visual short-term memory and learning were broadly within the average range for the overall sample at all three timepoints. However, a large percentage of children exhibited scores ≥1SD below the mean on tasks of verbal learning both immediately (43.4%) and after a delay (40.7%) at T3. In addition, 58.6% of children randomized to SDCSI exhibited impairment in verbal learning after a delay compared to 34.8% of children randomized to LDSCI, and 35.0% of those aged ≥8 at diagnosis receiving SDCSI. CONCLUSIONS Younger children receiving SDCSI have particularly high rates of memory impairment five years after diagnosis of medulloblastoma. Limiting CSI dose and/or volume in young children treated for this diagnosis may improve outcomes for memory functioning.

MBCL-15. IMPACT OF MOLECULAR SUBGROUPS ON OUTCOMES FOLLOWING RADIATION TREATMENT RANDOMIZATIONS FOR AVERAGE RISK MEDULLOBLASTOMA: A PLANNED ANALYSIS OF CHILDREN’S ONCOLOGY GROUP (COG) ACNS0331

The COG conducted a randomized trial for average-risk medulloblastoma (AR-MB). Patients age 3–21 years were randomized to a radiation boost to the whole posterior fossa (PFRT) or an involved field volume (IFRT) after receiving CSI. Patients age 3–7 years were also randomized to standard dose CSI (23.4Gy, SDCSI) or low dose CSI (18Gy, LDCSI). 464 evaluable patients were available to compare PFRT vs. IFRT and 226 for SDCSI vs. LDCSI. 380 cases had sufficient tissue for DNA methylation-based molecular classification: 362 confirmed medulloblastoma; 6 non-medulloblastoma; 12 inconclusive. Molecular subgrouping confirmed the following representation amongst the evaluable cohort: 156 Group 4 (43.1%), 76 Group 3 (21.0%), 66 SHH (18.2%), 64 WNT (17.7%). Five-year event-free survival (EFS) estimates were 82.5±2.7% and 80.5±2.7% for IFRT and PFRT, respectively (p=0.44). Five-year EFS estimates were 71.4±4.4% and 82.9±3.7% for LDCSI and SDCSI, respectively (p=0.028). EFS distributions differed significantly by subgroup (p<0.0001). Group 3 had the worst outcome, while WNT had the best outcome. There was a significant difference in EFS by RT group among SHH patients; SHH patients receiving IFRT arm had better EFS compared to PFRT (p=0.018). There was a significant difference in EFS distributions by CSI group in Group 4 patients; young Group 4 patients treated with SDCSI had better EFS compared to LDCSI (p=0.047). As previously reported, IFRT is noninferior to PFRT in all patients with AR-MB but LDCSI is worse than SDCSI in younger children. Significant differences in outcome by study randomization and molecular subgroup are observed.