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Population-based study of effectiveness of neoadjuvant radiotherapy on survival in US rectal cancer patients according to age.

ABSTRACT: Recent cancer researches pay more attention to younger patients due to the variable treatment response among different age groups. Here we investigated the effectiveness of neoadjuvant radiation on the survival of younger and older patients in stage II/III rectal cancer. Data was obtained from Surveillance, Epidemiology, and End Results (SEER) database (n?=?12801). Propensity score matching was used to balance baseline covariates according to the status of neoadjuvant radiation. Our results showed that neoadjuvant radiation had better survival benefit (Log-rank P?=?3.25e-06) and improved cancer-specific 3-year (87.6%; 95% CI: 86.4-88.7% vs. 84.1%; 95% CI: 82.8-85.3%) and 5-year survival rates (78.1%; 95% CI: 76.2-80.1% vs. 77%; 95% CI: 75.3-78.8%). In older groups (>50), neoadjuvant radiation was associated with survival benefits in stage II (HR: 0.741; 95% CI: 0.599-0.916; P?=?5.80e-3) and stage III (HR: 0.656; 95% CI 0.564-0.764; P?=?5.26e-08). Interestingly, neoadjuvant radiation did not increase survival rate in younger patients (

SUBMITTER: Wu L

PROVIDER: S-EPMC5471198 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Population-based study of effectiveness of neoadjuvant radiotherapy on survival in US rectal cancer patients according to age.

Wu Leilei L Pang Shichao S Yao Qianlan Q Jian Chen C Lin Ping P Feng Fangyoumin F Li Hong H Li Yixue Y

Scientific reports 20170614 1

Recent cancer researches pay more attention to younger patients due to the variable treatment response among different age groups. Here we investigated the effectiveness of neoadjuvant radiation on the survival of younger and older patients in stage II/III rectal cancer. Data was obtained from Surveillance, Epidemiology, and End Results (SEER) database (n = 12801). Propensity score matching was used to balance baseline covariates according to the status of neoadjuvant radiation. Our results show ...[more]

PMID: 28615639

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Project description:BACKGROUND:Neoadjuvant radiotherapy (RT) has been shown to improve local control; however, whether it can improve overall survival (OS) in locally advanced rectal cancer (LARC) patients remains controversial. We therefore aimed to examine the benefits of surgery alone, neoadjuvant radiotherapy (RT), adjuvant RT, and surgery plus chemotherapy in stage II (T3/4N0M0) and III (any T and N?+?M0) on the OS of rectal cancer patients. METHODS:Date from the Surveillance, Epidemiology, and End Results (SEER) database diagnosed between 2004 and 2016 were used. Kaplan-Meier analyses were used to compare patient prognoses across different treatment modalities. Cox hazard regression analysis were used to identify independent predictors of OS. RESULTS:For stage T3/4N0M0 patients, neoadjuvant RT, adjuvant RT, and surgery plus chemotherapy resulted in similar OS (all p?>?0.05; mean survival, 115.89?months (M), 111.97?M, and 117.22?M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p?<?0.001, mean survival, 88.96?M). For stage T1/2N?+?M0 patients, neoadjuvant RT, adjuvant RT, and surgery plus chemotherapy resulted in similar OS (all p?>?0.05; mean survival, 121.50?M, 124.25?M, and 121.20?M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p?<?0.001, mean survival 83.81?M). For stage T3/4N?+?M0 patients, neoadjuvant RT (HR?=?0.436; 95% CI, 0.396~0.478; p?<?0.001) resulted in significantly longer OS than adjuvant RT and surgery plus chemotherapy (mean survival, 104.47?M, 93.94?M, and 93.62?M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p?<?0.001, mean survival 54.87?M). Older age (>?60?years), black race, unmarried status, high tumour grade, and tumour size >?5?cm were all associated with a poor prognosis (all p?<?0.05). CONCLUSIONS:Neoadjuvant RT, adjuvant RT, and surgery plus chemotherapy results in better OS than surgery alone in LARC patients. Neoadjuvant RT has the potential to be highly recommended over adjuvant RT and surgery plus chemotherapy for T3/4N?+?M0 patients; however, it showed no OS advantage over adjuvant RT or surgery plus chemotherapy for T3/4N0M0 and T1/2N?+?M0 patients.

Project description:IntroductionIn locally advanced rectal cancer, longer delay to surgery after neoadjuvant radiotherapy increases the likelihood of histopathological tumour response. Chronomodulated radiotherapy in rectal cancer has recently been reported as a factor increasing tumour response to neoadjuvant treatment in patients having earlier surgery, with patients receiving a larger proportion of afternoon treatments showing improved response. This paper aims to replicate this work by exploring the impact of these two temporal factors, independently and in combination, on histopathological tumour response in rectal cancer patients.MethodsA retrospective review of all patients with rectal adenocarcinoma who received long course (≥24 fractions) neoadjuvant radiotherapy with or without chemotherapy at a tertiary referral centre was conducted. Delay to surgery and radiotherapy treatment time were correlated to clinicopathologic characteristics with a particular focus on tumour regression grade. A review of the literature and meta-analysis were also conducted to ascertain the impact of time to surgery from preoperative radiotherapy on tumour regression.ResultsFrom a cohort of 367 patients, 197 patients met the inclusion criteria. Complete pathologic response (AJCC regression grade 0) was seen in 46 (23%) patients with a further 44 patients (22%) having at most small groups of residual cells (AJCC regression grade 1). Median time to surgery was 63 days, and no statistically significant difference was seen in tumour regression between patients having early or late surgery. There was a non-significant trend towards a larger proportion of morning treatments in patients with grade 0 or 1 regression (p = 0.077). There was no difference in tumour regression when composite groups of the two temporal variables were analysed. Visualisation of data from 39 reviewed papers (describing 27379 patients) demonstrated a plateau of response to neoadjuvant radiotherapy after approximately 60 days, and a meta-analysis found improved complete pathologic response in patients having later surgery.ConclusionsThere was no observed benefit of chronomodulated radiotherapy in our cohort of rectal cancer patients. Review of the literature and meta-analysis confirms the benefit of delayed surgery, with a plateau in complete response rates at approximately 60-days between completion of radiotherapy and surgery. In our cohort, time to surgery for the majority of our patients lay along this plateau and this may be a more dominant factor in determining response to neoadjuvant therapy, obscuring any effects of chronomodulation on tumour response. We would recommend surgery be performed between 8 and 11 weeks after completion of neoadjuvant radiotherapy in patients with locally advanced rectal cancer.

Project description:BackgroundOnline adaptive radiotherapy has the potential to reduce toxicity for patients treated for rectal cancer because smaller planning target volumes (PTV) margins around the entire clinical target volume (CTV) are required. The aim of this study is to describe the first clinical experience of a Conebeam CT (CBCT)-based online adaptive workflow for rectal cancer, evaluating timing of different steps in the workflow, plan quality, target coverage and patient compliance.MethodsTwelve consecutive patients eligible for 5 × 5 Gy pre-operative radiotherapy were treated on a ring-based linear accelerator with a multidisciplinary team present at the treatment machine for each fraction. The accelerator is operated using an integrated software platform for both treatment planning and delivery. In all directions for all CTVs a PTV margin of 5 mm was used, except for the cranial/caudal borders of the total CTV where a margin of 8 mm was applied. A reference plan was generated based on a single planning CT. After aligning the patient the online adaptive procedure started with acquisition of a CBCT. The planning CT scan was registered to the CBCT using deformable registration and a synthetic CT scan was generated. With the support of artificial intelligence, structure guided deformation and the synthetic CT scan contours were adapted by the system to match the anatomy on the CBCT. If necessary, these contours were adjusted before a new plan was generated. A second and third CBCT were acquired to validate the new plan with respect to CTV coverage just before and after treatment delivery, respectively. Treatment was delivered using volumetric modulated arc treatment (VMAT). All steps in this process were defined and timed.ResultsOn average the timeslot needed at the treatment machine was 34 min. The process of acquiring a CBCT, evaluating and adjusting the contours, creating the new plan and verifying the CTV on the CBCT scan took on average 20 min. Including delivery and post treatment verification this was 26 min. Manual adjustments of the target volumes were necessary in 50% of fractions. Plan quality, target coverage and patient compliance were excellent.ConclusionsFirst clinical experience with CBCT-based online adaptive radiotherapy shows it is feasible for rectal cancer. Trial registration Medical Research Involving Human Subjects Act (WMO) does not apply to this study and was retrospectively approved by the Medical Ethics review Committee of the Academic Medical Center (W21_087 # 21.097; Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands).

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Population-based study of effectiveness of neoadjuvant radiotherapy on survival in US rectal cancer patients according to age.

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Population-based study of effectiveness of neoadjuvant radiotherapy on survival in US rectal cancer patients according to age.

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