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Role of the extent of prophylactic regional lymph node radiotherapy on survival in high-risk neuroblastoma: A report from the COG A3973 study.

ABSTRACT: PURPOSE:Neuroblastoma is the most common extracranial solid pediatric malignancy, with poor outcomes in high-risk disease. Standard treatment approaches employ an increasing array of aggressive multimodal therapies, of which local control with surgery and radiotherapy remains a backbone; however, the benefit of broad regional nodal irradiation remains controversial. We analyzed centrally reviewed radiation therapy data from patients enrolled on COG A3973 to evaluate the impact of primary site irradiation and the extent of regional nodal coverage stratified by extent of surgical resection. METHODS:Three hundred thirty high-risk neuroblastoma patients with centrally reviewed radiotherapy plans were analyzed. Outcome was evaluated by the extent of nodal irradiation. For the 171 patients who also underwent surgery (centrally reviewed), outcome was likewise analyzed according to the extent of resection. Overall survival (OS), event-free survival (EFS), and cumulative incidence of local progression (CILP) were examined by Kaplan-Meier, log-rank test (EFS, OS), and Grey test (CILP). RESULTS:The five-year CILP, EFS, and OS for all 330 patients receiving radiotherapy on A3973 were 8.5% ± 1.5%, 47.2% ± 3.0%, and 59.7% ± 3.0%, respectively. There were no significant differences in outcomes based on the extent of lymph node irradiation regardless of the degree of surgical resection (< 90% or ?90%). CONCLUSION:Although local control remains a significant component of treatment of high-risk neuroblastoma, our results suggest there is no benefit of extensive lymph node irradiation, irrespective of the extent of surgical resection preceding stem cell transplant.

SUBMITTER: Braunstein SE

PROVIDER: S-EPMC7281832 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Role of the extent of prophylactic regional lymph node radiotherapy on survival in high-risk neuroblastoma: A report from the COG A3973 study.

Braunstein Steve E SE London Wendy B WB Kreissman Susan G SG Villablanca Judith G JG Davidoff Andrew M AM DeSantes Kenneth K Castleberry Robert P RP Murray Kevin K Diller Lisa L Matthay Katherine K Cohn Susan L SL Shulkin Barry B von Allmen Daniel D Parisi Marguerite T MT Van Ryn Collin C Park Julie R JR La Quaglia Michael P MP Haas-Kogan Daphne A DA

Pediatric blood & cancer 20190409 7

<h4>Purpose</h4>Neuroblastoma is the most common extracranial solid pediatric malignancy, with poor outcomes in high-risk disease. Standard treatment approaches employ an increasing array of aggressive multimodal therapies, of which local control with surgery and radiotherapy remains a backbone; however, the benefit of broad regional nodal irradiation remains controversial. We analyzed centrally reviewed radiation therapy data from patients enrolled on COG A3973 to evaluate the impact of primary ...[more]

PMID: 30968542

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Project description:We aimed to assess the prognostic impact of tumor- and patient-related parameters in patients with stage I-III small intestinal neuroendocrine tumors (SI-NETs), who underwent locoregional resective surgery (LRS) with curative intent. We included 229 patients with stage I-III SI-NETs diagnosed from June 15, 1993, through March 8, 2021, identified using the SI-NET databases from five European referral centers. Mean ± SD age at baseline was 62.5 ± 13.6 years; 111/229 patients were women (49.3%). All tumors were well-differentiated; 160 were grade 1 (G1) tumors, 51 were G2, two were G3 and 18 tumors were of unspecified grade (median Ki-67: 2%, range 1%-50%). One-hundred and sixty-three patients (71.2%) had lymph node (LN) involvement. The median number of retrieved lymph nodes was 10 (0-63), whereas the median number of positive LNs was 2 (0-43). After a mean ± SD follow-up of 54.1 ± 64.1 months, 60 patients experienced disease recurrence at a median (range) of 36.2 (2.5-285.1) months. The 5- and 10-year recurrence-free survival (RFS) rates were 66.6% and 49.3% respectively. In univariable analysis, there was no difference in RFS and overall survival (OS) between LN-positive and LN-negative patients (log-rank, p = .380 and .198, respectively). However, in stage IIIb patients who underwent mesenteric lymph node dissection (MLND) with a minimum of five retrieved LN (n = 125), five or more LN metastases were associated with shorter RFS (median RFS [95% CI] = 107.4 [0-229.6] vs. 73.7 [35.3-112.1] months; log-rank, p = .048). In addition, patients with G2 tumors exhibited shorter RFS compared to patients with G1 tumors (median RFS [95% confidence interval (CI)] = 46.9 [36.4-57.3] vs. 120.7 [82.7-158.8] months; log-rank, p = .001). In multivariable Cox-regression RFS analysis in stage IIIb patients, the Ki-67 proliferation index (hazard ratio = 1.08, 95% CI = 1.035-1.131; p < .0001) and the number of LN metastases (hazard ratio = 1.06, 95% CI = 1.001-1.125; p = .047) were independent prognostic factors for RFS. In conclusion, LRS with a meticulous MLND and a minimum number of five harvested LNs appears to be critical in the surgical management of SI-NET patients with locoregional disease. In patients who underwent LRS and MLND, the Ki-67 proliferation index and the LN metastases count were independent predictors of RFS.

Project description:Purpose This analysis of patients in the Children's Oncology Group A3973 study evaluated the impact of extent of primary tumor resection on local progression and survival and assessed concordance between clinical and central imaging review-based assessments of resection extent. Patients and Methods The analytic cohort (n = 220) included patients who had both central surgery review and resection of the primary tumor site. For this analysis, resection categories of < 90% and ≥ 90% were used, with data on resection extent derived from operating surgeons' assessments (all patients), as well as blinded central imaging review of computed tomography scans for a subset of 84 patients; assessment results were compared for concordance. Treatment outcomes included event-free survival (EFS), overall survival (OS), and cumulative incidence of local progression (CILP). Results Surgeon-assessed extent of resection was ≥ 90% in 154 (70%) patients and < 90% in 66 (30%). Five-year EFS, OS, and CILP (± SE) were 43.5% ± 3.7%, 54.9% ± 3.7%, and 11.9% ± 2.2%, respectively. EFS was higher with ≥ 90% resection (45.9% ± 4.3%) than with < 90% resection (37.9% ± 7.2%; P = .04). Lower CILP ( P = .01) was associated with ≥ 90% resection (8.5% ± 2.3%) compared with < 90% resection (19.8% ± 5.0%). On multivariable analysis, ≥ 90% resection was associated with longer EFS after adjustment for MYCN amplification or diploidy but had no significant effect on OS. Concordance between surgeons' assessments of resection extent and central image-guided review was low, with agreement of 63% (< 90% v ≥ 90%; simple κ = -0.0301). Conclusion Despite discordance between clinical assessment of resection extent and assessment via central imaging review, a surgeon-assessed resection extent ≥ 90% was associated with significantly better EFS and lower CILP. Improving OS, however, remains a challenge in this disease. These findings support continued attempts at ≥ 90% resection of the primary tumor in high-risk neuroblastoma.

Project description:BackgroundWe evaluated the optimal radiotherapy (RT) plan for synchronous bilateral breast cancer (SBBC), especially treatment plans including the regional lymph node (LN) area.MethodsThis study was conducted using 15 patients with SBBC (5 with small breasts, 5 with large breasts, and 5 who underwent a left total mastectomy). The clinical target volume (CTV) was defined as the volume enveloping the bilateral whole breasts/chest wall and left regional LN area. We established the following plans: 1) volumetric-modulated arc therapy (VMAT)-the only plan using two pairs of partial arcs for the whole target volume, 2) VMAT using one partial arc for the left CTV followed by a 3D tangential technique for the right breast (primary hybrid plan), and 3) VMAT for the left CTV followed by a tangential technique using an automatically calculated prescription dose for the right breast, considering the background dose from the left breast VMAT plan (modified hybrid plan). The Tukey test and one-way analysis of variance were used to compare the target coverage and doses to organs at risk (OARs) of the three techniques.ResultsFor target coverage, the VMAT-only and modified hybrid plans showed comparable target coverage in terms of Dmean (50.33 Gy vs. 50.53 Gy, p = 0.106). The primary hybrid plan showed the largest distribution of the high-dose volume, with V105% of 25.69% and V110% of 6.37% for the planning target volume (PTV) (p < 0.001). For OARs including the lungs, heart, and left anterior descending artery, the percentages of volume at various doses (V5Gy, V10Gy, V20Gy, V30Gy) and Dmean were significantly lower in both the primary and modified hybrid plans compared to those of the VMAT-only plan. These results were consistent in subgroup analyses of breast size and morphological variation.ConclusionsThe modified hybrid plan, using an automatically calculated prescription dose for the right breast and taking into consideration the background dose from the left breast VMAT plan, showed comparable target coverage to that of the VMAT-only plan, and was superior for saving OARs. However, considering that VMAT can be adjusted according to the physician's intention, further evaluation is needed for developing a better plan.

Project description:Clinical trials evaluating the benefit of pelvic radiotherapy (PRT) in the radiotherapeutic management of patients with higher-risk prostate cancer have limited the superior field border to the S1/S2 or L5/S1 interspace. However, imaging and surgical series have demonstrated a high frequency of prostatic lymph node (LN) drainage beyond these landmarks.To determine the patterns of radiographically defined abdominopelvic LN failures and their potential implications for PRT field design.During 1992-2008, 2694 patients with localized prostate cancer were treated with prostate/seminal vesicle-only radiotherapy without PRT. Some 156 patients had their first failure within the abdominopelvic LNs, of whom 60 had isolated failures within the pelvic LNs.A radiologist reviewed all imaging and mapped each LN failure to a template consisting of 34 abdominopelvic LN stations.The median follow-up was 8.9 yr. Of patients who experienced first recurrence in the pelvic LNs (n=60), the common iliac station was involved in 55% (n=33) of patients, including 10% (n=6) who had isolated common iliac failures. Use of a PRT field superior border of L5/S1 would fully cover only 42% of the first recurrences among these patients. Extending the field to cover the common iliac stations would increase coverage to 93% of recurrences. The presence of T3/T4 disease and omission of androgen-deprivation therapy both independently conferred an approximate fivefold increase in the likelihood of having a common iliac LN failure. Use of imaging as a surrogate for LN involvement is the primary study limitation.Pelvic LN failures frequently occur superior to the commonly used L5/S1 landmark for PRT coverage, and use of ADT may be protective of more superior LN failures. The current RTOG 0924 trial is evaluating the benefit of PRT with extended superior coverage to L4/5 when possible, which, according to our data, should significantly improve the coverage of potential sites of failure.We looked at lymph node recurrence patterns after external beam radiotherapy of the prostate in men who did not have their lymph nodes treated. We found that there was a high incidence of pelvic lymph node recurrences above the internal and external iliac lymph node regions. Therefore, the current field recommendation for pelvic lymph nodes that stops at the superior border of the internal and external iliac vessels provides inadequate coverage of common sites of cancer recurrence, namely the common iliac lymph nodes.

Project description:BackgroundYoung breast cancer (YBC) patients demonstrate a heightened propensity for regional lymph node metastasis (RLNM) in contrast to cohorts across varying age demographics. The aim of our study was to identify clinicopathologic prognostic variables in YBC patients with RLNM and construct a practical and reliable nomogram for the prediction of overall survival (OS) using the Surveillance, Epidemiology, and End Results (SEER) database.MethodsYoung individuals (≤40 years) with a diagnosis of breast cancer with RLNM were recognized from the SEER database between 2010 and 2015, and further randomly split into two cohorts: the training set (n=4,497) and the validation set (n=1,927). We first performed univariate and multivariate Cox regression analyses to confirm independent survival predictors of OS. A novel prognostic nomogram was developed and evaluated using Harrell's concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). To make a clear distinction between high- and low-risk patients in terms of patient survival, Kaplan-Meier survival curves were assessed using the log-rank test.ResultsNine risk factors were found as independent prognostic variables in predicting OS, including race, grade, histology, surgery, radiation, molecular subtype, American Joint Committee on Cancer (AJCC) stage 7th edition, T stage, and N stage. The C-index values of our nomogram were 0.786 [95% confidence interval (CI): 0.767-0.805] and 0.791 (95% CI: 0.760-0.822) in our training and validation groups, respectively. The ROC curves demonstrated sufficient discriminating ability, while the predicted and real survival rates were fairly consistent, as shown by the calibration plots. The prediction model had a higher net benefit and acceptable clinical value, as shown by the DCA curves.ConclusionsIn YBC patients with RLNM, we successfully established a unique nomogram to forecast the 2-, 3-, and 5-year OS. Clinicians may utilize this nomogram to pinpoint patients at higher risk and provide them with appropriate customized therapies.

Dataset Information

Role of the extent of prophylactic regional lymph node radiotherapy on survival in high-risk neuroblastoma: A report from the COG A3973 study.

Publications

Role of the extent of prophylactic regional lymph node radiotherapy on survival in high-risk neuroblastoma: A report from the COG A3973 study.

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