Neoadjuvant Radiation Dose Research Articles

Radiation dose and pathological response in oesophageal cancer patients treated with neoadjuvant chemoradiotherapy followed by surgery: a multi-institutional analysis

Purpose: To explore whether a higher neoadjuvant radiation dose increases the probability of a pathological complete response (pCR) or pathological major response (pMR) response in oesophageal cancer patients.Material and methods: Between 2000 and 2017, 1048 patients from four institutions were stratified according to prescribed neoadjuvant radiation doses of 36.0 Gy (13.3%), 40.0 Gy (7.4%), 41.4 Gy (20.1%), 45.0 Gy (25.5%) or 50.4 Gy (33.7%) in 1.8–2.0 Gy fractions. Endpoints were pCR (tumour regression grade (TRG) 1) and pMR (TRG 1 + 2). Multivariable binary (TRG 1 + 2 vs. TRG > 2) and ordinal (TRG 1 vs. TRG 2 vs. TRG > 2) logistic regression analyses were performed, with subgroup analyses according to histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC)). Variables entered in the regression model along with neoadjuvant radiation dose were clinical tumour stage (cT), histology, chemotherapy regimen, induction chemotherapy and time from neoadjuvant chemoradiation to surgery.Results: A pCR was observed in 312 patients (29.8%); in 22.7% patients with AC and in 49.6% patients with SCC. No radiation dose–response relation was observed for pCR (OR = 1.01, 95% CI: 0.98–1.05 for AC and OR = 1.03, 95% CI: 0.96–1.10 for SCC). A pMR was observed in 597 patients (57.0%); in 53.4% patients with AC and in 67.2% patients with SCC. A higher radiation dose increased the probability of achieving pMR (OR = 1.04, 95% CI: 1.02–1.05). Factors reducing this probability were advanced cT stage (reference = cT1–2; cT3: OR = 0.54, 95% CI: 0.37–0.80; cT4: OR = 0.45, 95% CI: 0.24–0.84), AC histology (reference = SCC; OR = 0.62, 95% CI: 0.44–0.88), the use of non-platinum based chemotherapy in SCC patients (OR = 0.30, 95% CI: 0.10–0.91) and platinum based chemotherapy without induction chemotherapy in patients with AC (OR = 0.56, 95% CI: 0.42–0.76). The radiation dose–response relation was confirmed in a subgroup analysis of histologic subtypes (OR = 1.02, 95% CI: 1.01–1.04 for AC and OR = 1.05, 95% CI: 1.02–1.08 for SCC).Conclusions: Neoadjuvant radiation dose impacts pathological response in terms of pMR in oesophageal cancer patients. No radiation dose–response effect was observed for pCR. Further prospective trials are needed to investigate the dose–response relation in terms of pCR

Analyzing the impact of neoadjuvant radiation dose on pathologic response and survival outcomes in esophageal and gastroesophageal cancers.

The optimal neoadjuvant radiation therapy (RT) dose prior to esophagectomy is unknown. We compared patients receiving lower-dose RT (LD-RT) of 41.4-45 Gy versus those receiving higher-dose RT (HD-RT) of 50-54 Gy. Patients with non-metastatic esophageal or gastroesophageal cancer diagnosed from 2004 to 2015 who underwent neoadjuvant chemoradiation (CRT) followed by esophagectomy were identified using the National Cancer Database (NCDB) and divided into LD-RT and HD-RT groups. Logistic regression was used to evaluate predictors of HD-RT utilization and propensity score matching. Overall survival (OS) was compared between HD-RT and LD-RT groups using Cox regression. Logistic regression was performed with respect to pathologic complete response (pCR), positive surgical margins, postoperative mortality, and readmission rates. We identified 7,996 patients meeting inclusion criteria, of which 5,732 (71.7%) received HD-RT. At median follow-up of 3.3 years, 3-year OS was 48.7% for HD-RT versus 48.4% for LD-RT (P=0.734). pCR rates were 20.3% with HD-RT versus 16.3% with LD-RT [odds ratio (OR) 1.24; 95% CI: 1.06-1.44; P=0.006]. There were no statistically significant differences between HD-RT and LD-RT with respect to positive margins, 90-day postoperative mortality, or readmission rates. In a separate analysis of patients treated with CRT alone and no subsequent esophagectomy, HD-RT was associated with improved OS (HR 0.83; 95% CI: 0.78-0.88; P<0.001). Our analysis suggests that 41.4-45 and 50-54 Gy dose regimens are similar in survival and postoperative outcomes. However, in cases of equivocal resectability, a higher RT dose of 50-54 Gy may be preferred.

Influence of Neoadjuvant Radiation Dose on Patients Undergoing Esophagectomy and Survival in Locally Advanced Esophageal Cancer

BackgroundNeoadjuvant chemoradiotherapy followed by resection is standard of care for patients with locally advanced esophageal cancer, however, a significant portion of these patients do not undergo surgical intervention. This study evaluates radiation dose and other factors associated with undergoing esophageal resection and their impact on outcomes including survival. MethodsPatients diagnosed with esophageal cancer between 2010 and 15 were queried from the National Cancer Database and stratified into low-dose radiation (41.4 Gy) (LDR) or high-dose radiation (50.0 or 50.4 Gy) (HDR) groups. Multivariable Logistic and Cox Regression analyses were performed to investigate the effect of multiple variables on the likelihood of undergoing esophagectomy and overall survival, respectively. Propensity score matching was performed to reduce bias between groups. ResultsA total of 3633 patients met study criteria with 3005 (82.7%) undergoing esophagectomy. A greater proportion received HDR (3163 (87.1%)) than LDR (470 (12.9%)). The use of LDR increased from 4.7% (n = 22) in 2010 to 20.7% (n = 154) in 2015. Factors associated with undergoing esophagectomy included LDR, adenocarcinoma histology, and younger age. Radiation dosage did not impact overall survival, but undergoing esophagectomy was associated with improved survival. After propensity matching, a greater portion of the LDR group underwent esophagectomy (87.0 vs 81.1%, p = 0.013). There was no difference in R0 3 resection (93.2 vs 92.4%, p = 0.678) or complete pathologic response (19.3 vs 21.5%, p = 0.442) between LDR and HDR groups. ConclusionThe use of LDR is increasing but still underutilized. LDR is associated with increased rates of esophagectomy without negatively impacting overall survival, R0 resection, or complete pathologic response.

Pathologic nodal clearance and complete response following neoadjuvant chemoradiation for clinical N2 non-small cell lung cancer: Predictors and long-term outcomes

PurposeFrom prospective studies, pathologic nodal clearance (PNC, ypN0) and pathologic complete response (pCR, ypT0N0) correlate with overall survival (OS) following neoadjuvant chemoradiation for cN2 non-small cell lung cancer (NSCLC). Contemporary cooperative group trials attempt to increase radiation doses to achieve nodal clearance and/or pCR. However, long-term comparative outcomes of dose-escalated neoadjuvant chemoradiation are lacking. The goal of this study was to evaluate rates of PNC and pCR in a large population of cN2 NSCLC, predictors thereof, and long-term outcomes thereafter. MethodsThe National Cancer Database was queried (2004–2015) for histologically-confirmed cT1-4N2M0 NSCLC undergoing neoadjuvant chemoradiation followed by lobectomy. Statistics included multivariable logistic regression, Kaplan-Meier OS analysis before and following propensity matching, Cox proportional hazards modeling, and sensitivity analysis when varying neoadjuvant radiation dose. ResultsOf 1750 patients, the pCR and PNC rates were 17% and 37%, respectively. Radiation dose >54 Gy independently predicted for pCR. Patients achieving pCR experienced significantly higher OS than non-pCR cases (p < 0.001) and ypT + ypN0 cases (p < 0.001). In the subset of non-PNC patients, there was a trend towards higher OS in patients in whom ypT0 was achieved (p = 0.059). On sensitivity analysis, when separating the cohort into doses of 45.0–50.4 Gy, 50.5–54.0 Gy, 54.1–59.4 Gy, and >59.4 Gy, 30-day mortality rates in the respective groups were 2.9%, 1.8%, 1.2%, and 3.4%. ConclusionsAlthough neoadjuvant dose-escalation increases pCR rates, there is no OS benefit with dose-escalation, and high dose-escalation (i.e., >59.4 Gy) was associated with numerically higher mortality rates, indicating the importance of careful multidisciplinary discussion.

PV-0099: Neoadjuvant radiation dose to the lungs and the risk of postoperative pneumonia in esophageal cancer

PV-0099: Neoadjuvant radiation dose to the lungs and the risk of postoperative pneumonia in esophageal cancer

EP-1480: Neoadjuvant radiation dose to the anal sphincter and postoperative bowel function in rectal cancer

EP-1480: Neoadjuvant radiation dose to the anal sphincter and postoperative bowel function in rectal cancer

Neoadjuvant chemoradiation radiation dose levels for surgically resectable esophageal cancer: predictors of use and outcomes.

Neoadjuvant chemoradiation (CRT) followed by surgical resection is the standard of care for resectable, locally advanced esophageal cancer. There are promising results using 41.4 Gy relative to historical controls using higher doses, but the utilization and efficacy of lower neoadjuvant radiation dosing is unclear. This study uses the National Cancer Database (NCDB) to explore patterns of care for neoadjuvant CRT dose levels and outcomes. The NCDB was queried for localized invasive esophageal adenocarcinoma (AC) or squamous cell carcinoma (SCC) receiving neoadjuvant CRT with doses from 40 to 54 Gy followed by surgical resection. Patients were divided into radiation levels: 40-41.4, 45, 50.4, and 54 Gy, respectively. Factors predicting use of 40-41.4 Gy vs. all other dose levels were compared using multivariable logistic regression. Factors affecting overall survival (OS) were compared using univariate and multivariate modeling. A total of 6,274 patients with AC (n=5,176) or SCC (n=1,098) receiving neoadjuvant CRT and definitive resection were identified. Hispanic race (OR 2.67 [95% CI 1.22-5.81]) and treatment at an academic center (OR 2.72 [95% CI 1.15-6.41]) predicted for use of low-dose CRT. Lower dose CRT increased from 3.9% in 2004 to 7.2% in 2013. There was no difference in OS when stratified according to radiation dose level (P=0.48). Multivariable analysis found private/government insurance, higher education, higher median income, and treatment at an academic center were associated with improved OS. Age, male gender, Charlson-Deyo comorbidity score, stage, tumor grade, and treatment in the South were associated with worse OS. Use of lower neoadjuvant CRT dose is more common at academic centers and shows possible increasing usage. Neoadjuvant radiation dose for esophageal cancer is not associated with differences in OS in this large database.

Is Higher Dose Radiation Beneficial As Part of a Neoadjuvant Chemoradiation Therapy Protocol for Resectable Esophageal Cancer? A Meta-analysis

Neoadjuvant chemoradiation therapy (NCRT) for resectable esophageal carcinoma has improved survival rates in patients with locally advanced disease. However, the appropriate neo-adjuvant radiation dose is debated. This meta-analysis aims to evaluate if as part of a NCRT protocol, radiation dose affects survival in patients with locally advanced esophageal cancer. A comprehensive search of MEDLINE, EMBASE, PubMed, SCOPUS and the Cochrane database was conducted (1996-present). All randomized control trials of patients with esophageal carcinoma undergoing NCRT compared to surgery alone were included; study quality was assessed using CONSORT checklist. Pooled risk ratio along with the 95% confidence interval (CI) for overall survival (OS) and progression-free survival (PFS) at 1, 3 and 5 years were calculated. Search strategy yielded 111 studies, of which 10 studies met the selection criteria with a total of 1628 patients: 813 received NCRT, and 815 had surgery upfront. Meta-analysis of included data showed an increased OS at 1, 3, and 5-years (RR=1.10, 95% CI:0.99 – 1.22, p=0.09; RR=1.29, 95% CI:0.98 – 1.70, p = 0.07; RR= 1.39, 95% CI: 1.16 – 1.85, p <0.01, respectively); and PFS at 1, 3, and 5-years (RR=1.16, 95% CI 0.91 – 1.49, p=0.24; RR=1.37, 95% CI:1.14 – 1.65; p <0.01; RR=1.57, 95% CI:1.24 – 1.99; p <0.01, respectively) for NCRT group. For patients treated with NCRT, 584 were treated with less than 45 Gy, and 229 were treated with 45 Gy or more. Subgroup analysis showed significantly improved survival at 3, and 5-years (RR=1.38, 95%CI: 1.11 – 1.72, p<0.01; RR=1.40, 95% CI: 1.14–1.72; p<0.01, respectively) with patients treated at less than 45 Gy. Neoadjuvant chemoradiation therapy improves OS at 5 years in locally advanced esophageal cancer. This effect is especially pronounced in patients treated with less than 45 Gy as part of NCRT. Further prospective study of appropriate radiation dose for NCRT is warranted.

Neoadjuvant Chemoradiation Dose and Outcomes in Esophageal Cancers, a National Cancer Data Base Study

With excellent outcomes with lower dose chemoradiation (CRT) for neoadjuvant treatment of esophageal cancer followed by surgical resection, recent interest in the optimal radiation dose has arisen, specifically whether low dose CRT is as effective as higher doses. We looked at neoadjuvant radiation dose and outcomes in the National Cancer Database (NCDB). The NCDB for esophageal cancer from years 2004-2012 was queried for patients receiving neoadjuvant CRT followed by surgical resection with curative intent. Patients were excluded if they did not have squamous cell carcinoma (SCC) or adenocarcinoma (AC), had metastatic disease, or insufficient follow up. Cox proportional hazards model was used to identify variables that predict for overall survival. Linear regression was used to determine odds ratio of receipt of treatment. We identified 7,325 patients receiving neoadjuvant CRT followed by definitive resection: 1,276 SCC and 6,049 AC. Median follow-up was 26.3 months. We examined 4 radiation dose levels: 4000-4140 cGy (n = 252), 4500 cGy (n = 2,075), 5040 cGy (n = 4,451), and 5400 cGy (n = 547). The utilization of low dose (4000-4140 cGy) radiation has increased from 5.6% in 2010 to 31.5% in 2013. There was no significant difference between groups based on age, race, gender, insurance status, and distance from facility. Age over 60 (HR = 1.09, P = 0.032), AC histology (HR = 1.19, P = 0.001), and increasing stage (HR = 1.69, P < 0.00) were significant negative predictors of survival. Patients with Medicare/Medicaid had higher risk of death than those with private insurance (HR = 1.26, P < 0.00). Treatment at an academic center had improved survival (HR = 0.86, P < 0.00) and had higher odds ratio of receiving lowest radiation dose level (OR = 1.14, P < 0.00). After adjusting for all significant predictors of survival, radiation dose level was not associated with differences in overall survival (P = 0.39) or pathologic complete response (P = 0.21). There was also no difference in 30 or 90 day survival (P = 0.75 and 0.36, respectively). In the NCDB, there was no difference in pCR or OS when using low dose neoadjuvant CRT versus higher doses. Lower dose CRT appears to be increasing in utilization, especially in academic centers.

Effect of Neoadjuvant Radiation Dose and Schedule on Nodal Count and Its Prognostic Impact in Stage II-III Rectal Cancer.

It is unknown how neoadjuvant treatment schedule affects lymph node count (LNC) and lymph node ratio (LNR) and how these correlate with overall survival (OS) in rectal cancer (RC). Data were used from the Belgian PROCARE rectal cancer registry on RC patients treated with surgery alone, short-term radiotherapy with immediate surgery (SRT), or chemoradiation with deferred surgery (CRT). The effect of neoadjuvant therapy on LNC was examined using Poisson log-linear analysis. The association of LNC and LNR with overall survival (OS) was studied using Cox proportional hazards models. Data from 4037 patients were available. Compared with surgery alone, LNC was reduced by 12.3% after SRT and by 31.3% after CRT (p<0.001). In patients with surgery alone, the probability of finding node-positive disease increased with LNC, while after SRT and CRT no increase was noted for more than 12 and 18 examined nodes, respectively. Per node examined, we found a decrease in hazard of death of 2.7% after surgery alone and 1.5% after SRT, but no effect after CRT. In stage III patients, the LNR but not (y)pN stage was significantly correlated with OS regardless of neoadjuvant therapy. Specifically, a LNR>0.4 was associated with a significantly worse outcome. Nodal counts are reduced in a schedule-dependent manner by neoadjuvant treatment in RC. After chemoradiation, the LNC does not confer any prognostic information. A LNR of>0.4 is associated with a significantly worse outcome in stage III disease, regardless of neoadjuvant therapy type.

Effect of Neoadjuvant Radiation Dose on Surgical and Oncological Outcome in Locally Advanced Esophageal Cancer

Introduction : Neoadjuvant chemoradiation (CRT) confers a survival benefit in locally advanced esophageal cancer. The optimal dose of radiotherapy remains undefined.Methods : From a prospective database, we identified patients who received CRT followed by Ivor Lewis esophagectomy. Surgical complications, pathological response, and oncological outcome were compared between patients who received a radiotherapy (RT) dose of 36 Gy (group1) versus a dose of > 40 Gy (group 1).Results : 147 patients were evaluated: 109 received 36 Gy, while 38 received 41–50Gy. Mean age was 61 ± 9 years (84% male). Median hospital stay was 16 days. Anastomotic leakage occurred in 4.0%. Pulmonary complications occurred in 41.8%, neither being influenced by RT dose. Complete resection (R0) was achieved in 95% (group 1) and 100% (group 2), P = 0.3. Pathological complete response (pCR) was observed in 19% (group 1) and 37% (group 1), P = 0.04. Local recurrence developed in 9% in group 1, and 3% in group 2 (P = 0.3), but regional recurrence developed significantly higher in the low dose group (18% vs 3%, P < 0.001). Metastatic recurrence occurred in 48% in group 1 and 13% in group 1 (P < 0.001).Conclusions : In patients with locally advanced esophageal cancer a higher RT dose does not affect surgical outcome, enhances pCR rate, and reduces the locoregional and metastatic recurrence risk.

Correlation in Rectal Cancer Between Clinical Tumor Response After Neoadjuvant Radiotherapy and Sphincter or Organ Preservation: 10-Year Results of the Lyon R 96-02 Randomized Trial

To investigate, in rectal cancer, the benefit of a neoadjuvant radiation dose escalation with endocavitary contact radiotherapy (CXRT) in addition to external beam radiotherapy (EBRT). This article provides an update of the Lyon R96-02 Phase III trial. A total of 88 patients with T2 to T3 carcinoma of the lower rectum were randomly assigned to neoadjuvant EBRT 39 Gy in 13 fractions (43 patients) vs. the same EBRT with CXRT boost, 85 Gy in three fractions (45 patients). Median follow-up was 132 months. The 10-year cumulated rate of permanent colostomy (CRPC) was 63% in the EBRT group vs. 29% in the EBRT+CXRT group (p < 0.001). The 10-year rate of local recurrence was 15% vs. 10% (p = 0.69); 10-year disease-free survival was 54% vs. 53% (p = 0.99); and 10-year overall survival was 56% vs. 55% (p = 0.85). Data of clinical response (CR) were available for 78 patients (36 in the EBRT group and 42 in the EBRT+CXRT group): 12 patients were in complete CR (1 patient vs. 11 patients), 53 patients had a CR ≥ 50% (24 patients vs. 29 patients), and 13 patients had a CR <50% (11 patients vs. 2 patients) (p < 0.001). Of the 65 patients with CR ≥ 50%, 9 had an organ preservation procedure (meaning no rectal resection) taking advantage of major CR. The 10-year CRPC was 17% for patients with complete CR, 42% for patients with CR ≥ 50%, and 77% for patients with CR <50% (p = 0.014). In cancer of the lower rectum, CXRT increases the complete CR, turning in a significantly higher rate of long-term permanent sphincter and organ preservation.