Alteration of apparent diffusion coefficient measurements predict survival outcomes during neoadjuvant chemoradiotherapy in locally advanced rectal cancer

doi:10.21203/rs.3.rs-3238401/v1

Download PDF

Research Article

Alteration of apparent diffusion coefficient measurements predict survival outcomes during neoadjuvant chemoradiotherapy in locally advanced rectal cancer

https://doi.org/10.21203/rs.3.rs-3238401/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background

Neoadjuvant chemoradiation therapy (nCRT) followed by surgery is recommended for patients with locally advanced rectal cancer (LARC). However, because 30–40% of patients with LARC do not respond to nCRT, better prediction of treatment responses and survival outcomes is required. Therefore, we aimed to identify apparent diffusion coefficient (ADC) values that predict survival outcomes after nCRT in patients with LARC.

Methods

We analyzed 66 patients with LARC who underwent nCRT and evaluated ADC values of pre- and post-nCRT. We performed Cox proportional hazard regression analyses for survival outcomes.

Results

There were no significant differences in disease-free survival (DFS) and overall survival (OS) between low and high ADC values of pre-nCRT. However, patients classified as low ADC in post-nCRT had a significantly worse prognosis in OS and DFS (OS: P = 0.01; DFS: P < 0.01) than patients classified as high ADC. Moreover, an alteration in ADC values between pre- and post-nCRT was associated with poor OS (univariate: hazard ratio [HR] = 4.52, 95% confidence interval [CI] = 1.58–12.97, P < 0.01; multivariate: HR = 6.38, 95% CI = 1.48–27.56, P = 0.01). Finally, we identified ADC values that were significantly superior for predicting tumor regression grade with remarkable diagnostic accuracy (post-nCRT: area under the curve [AUC] = 0.79; alteration-nCRT: AUC = 0.85).

Conclusions

We identified the clinical importance of alteration of ADC values to predict the survival outcomes in patients with LARC. These results highlight the clinical importance of ADC values on improving the treatment strategies of patients.

Neoadjuvant chemoradiation therapy

ADC values

prognostic marker

rectal cancer

Colorectal cancer is one of the most common cancers worldwide, and 60,000–70,000 patients are diagnosed with locally advanced rectal cancer (LARC) each year (1–3). Combination treatment with neoadjuvant chemoradiotherapy (nCRT), radical surgery, and adjuvant chemotherapy is the gold standard treatment for patients with LARC (4–6). Although nCRT achieves a pathological complete response for approximately 15–30% of patients with LARC, it correlates to significantly postoperative dysfunctions. 30–40% of patients with LARC were non-responders to neoadjuvant therapy, who can be defined as no tumor regression changes based on resected specimens after nCRT. Unfortunately, the histopathological response is known only after surgery. Therefore, higher accuracy to predict treatment responses and survival outcomes before surgery is important in clinical settings.

Computed tomography (CT) and magnetic resonance imaging (MRI) provide parameters that reflect tumor characteristics, which have shown higher accuracy for the differentiation of responders from non-responders (7). Diffusion-weighted MRI (DWI) by using the apparent diffusion coefficient (ADC) values has been reported as a biomarker of malignancy, and it could provide a biological context associated with tumor cellularity and cell membrane integrity following nCRT (8–10). These accumulating reports have shown the potential role of ADC to predict tumor responses and survival outcomes after treatment. Additionally, the ADC correlates to histological features and cell counts, but its role to predict and monitor the response to nCRT remains controversial in LARC (11). Only a few studies have demonstrated the possibilities of prediction of responses to nCRT based on ADC values. In the present study, by analyzing changes in ADC values that can be easily used in clinical for patients with LARC before and after nCRT, we examined the significance of ADC values in predicting the probability of downstaging and favorable survival outcomes.

Patient cohorts

We have enrolled 66 patients with LARC who underwent radical resection followed by nCRT at Tokushima University Hospital between 2008 and 2017. All patients were diagnosed with LARC by pathologists according to the International Union for Cancer Control update of the Tumor-Node-Metastasis staging system. These patients underwent nCRT, and ADC values were evaluated from MRI before and after treatment. The exclusion criteria were no nCRT, non-adenocarcinoma, unavailable clinical information, or unavailable MRI examinations during pre- and post- treatment to allow accurate ADC measurements. The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of the University of Tokushima Graduate School (approval ID number: 3215).

nCRT and pathological assessment

The main nCRT included a fluorouracil-based regimen. Preoperative radiation therapy was performed total 45 Gy (five fractions per week and 1.8 Gy per fraction) to the entire pelvis. Radical resection with total mesorectal excision and D3 lymphadenectomy were performed after nCRT. Pathological responses to nCRT were assessed according to the tumor regression grade (TRG). Based on TRG classification, the patients were classified into a responder group (more than grade 2) and a non-responder group (grade 0 and 1).

Evaluation of ADC values

Routine examinations before treatment included complete physical and previous history assessments; chest, abdominal, and pelvic CT scans; and endoscopy. By using the fast spin-echo T2-weighted and DWI images, the mean ADC values (×10^− 3 mm²/s) of tumors were investigated in regions of interest (ROI) from ADC maps with manual tracing by using Synapse Vincent software (FujiFilm Medical, Japan), which could automatically calculates the mean values (12, 13). ROIs included most areas of solid tumor portions. We used the mean value of ADC as the cut-off to divide the patients into ADC-low and high groups. Same cut-off values were used in pre- and post- nCRT.

Statistical analysis

The cut-off thresholds were divided continuous variables by the mean value. The clinicopathological patient characteristics were compared between non-responder and responder groups by using the Mann–Whitney U test or chi-square test for categorical data. Overall survival (OS) and disease-free survival (DFS) were analyzed by the Kaplan–Meier method. Univariate and multivariate Cox proportional hazard regression models were used to identify independent prognostic markers. A P value < 0.05 was considered statistically significant. Statistical analyses were performed using JMP Pro ver13 statistical software (SAS Institute Japan, Tokyo, Japan) and Medcalc statistical software V.16.2.0 (Medcalc Software bvba, Ostend, Belgium).

Patient characteristics

We analyzed 66 patients with clinical stage II–III who were diagnosed with LARC before treatment. All patients underwent nCRT and received standard radical surgery (rectal resection with total mesorectal excision and lymphadenectomy). The detailed clinicopathological characteristics of these patients are provided in Table 1. The mean ADC values before and after nCRT were 1.46 (range: 0.76–1.99 × 10^− 3 mm²/s) and 1.60 (range: 0.89–2.24 × 10^− 3 mm²/s), respectively. In addition, alterations in ADC values between pre- and post-nCRT were observed (Fig. 1). The ADC values of 51 patients were increased, and those of 15 patients were decreased from pre-nCRT to post-nCRT. The tumor size, the clinical stage after nCRT, regimen, TRG, and LCR (lymphocyte to c-reactive protein ratio) were significantly associated with ADC values in alteration-nCRT.

The correlation of ADC values and TRG

Since the ADC values was associated with the tumor malignancy, we examined the correlation between TRG and ADC values. The alteration in ADC values between pre- and post-nCRT was correlated to the TRG with an area under the curve (AUC) value of 0.85 (95% confidence interval [CI] = 0.74–0.93, P < 0.01; Fig. 2C, D), compared with the ADC values pre-nCRT and post-nCRT (pre-nCRT; AUC = 0.54, 95% CI = 0.41–0.67, P = 0.57; Fig. 2A and post-nCRT; AUC = 0.79, 95% CI = 0.67–0.88, P < 0.01; Fig. 2B). We next determined the specific diagnostic performance of ADC alteration values for predicting TRG; the sensitivity, specificity, positive predictive value, and negative predictive value were 91.7%, 66.7%, 76.7%, and 87.0%, respectively (Table 2). This highlights that the alterations in ADC values are superior for identifying TRG in patients with LARC.

Table 1. Clinicopathological characteristics according to the alteration of ADC value between pre- and post-nCRT
	Alteration-nCRT
Factors	Down (n=15)		Up (n=51)	p
Age
(Median+SD)		68.7+3.2	65.7+1.3	0.31
Gender
Male		11	36
Female		4	15	0.84
Tumor size
(Median+SD)		39.0+6.4	24.1+2.4	0.04
Pre-nCRT Stage
II		5	19
IIIa		5	18
IIIb		5	14	0.86
Post-nCRT Stage
I		0	10
II		7	28
IIIa		3	11
IIIb		4	2	0.04
CEA level
≥5 ng/mL		3	2
<5 ng/mL		12	49	0.06
CA19-9 level
≥37 U/mL		4	5
<37 U/mL		11	46	0.11
Adjuvant therapy
Yes		6	9
No		8	42	0.06
NAC regimen
UFT		3	10
S-1		10	26
SOX+bev		2	15	0.02
TRG
0, 1		13	22
2, 3		2	29	0.01
LCR
(Median+SD)		6437+2204	11079+1331	0.04
NLR
(Median+SD)		7.9+2.4	4.1+0.6	0.09
PNI
(Median+SD)		38.5+2.6	42.7+0.9	0.27

ADC, apparent diffusion coefficient; CA19-9, carbohydrate antigen 19-9; CEA, carcinoembryonic antigen; LCR, lymphocyte to c-reactive protein ratio; nCRT, neoadjuvant chemoradiotherapy; NAC, neoadjuvant chemotherapy; NLR, neutrophil-to-lymphocyte ratio; PNI, prognostic nutritional index; SD, standard deviation: TRG, Tumor regression grade

Table 2

Performance of the model in estimating the risk of response
Variable	Value (95% CI)
Variable	Pre-nCRT	Post-nCRT	Alteration-nCRT
Sensitivity, %	88.9 (73.9–96.9)	72.2 (54.8–85.8)	91.7 (77.5–98.2)
Specificity, %	33.3 (17.3–52.8)	76.7 (57.7–90.1)	66.7 (47.2–82.7)
AUC, %	54.2 (41.4–66.5)	78.8 (67.0-87.9)	84.9 (73.9–92.5)
PPV, %	61.5 (54.8–67.9)	78.8 (65.3–88.0)	76.7 (66.3–84.7)
NPV, %	71.4 (46.6–87.8)	69.7 (56.7–80.1)	87.0 (68.7–95.3)
P value	0.57	< 0.01	< 0.01

AUC, area under the curve; CI, confidence interval; nCRT, neoadjuvant chemoradiotherapy; NPV, negative predictive value; PPV, positive predictive value

ADC values exhibited prognostic potential to predict survival outcomes in patients with LARC

To evaluate the prognostic potential of ADC values, we performed survival analysis to compare OS and DFS in patients who underwent nCRT and radical surgery. There were no significant differences in survival outcomes between patients categorized as high and low ADC in pre-nCRT (OS: P = 0.48 and DFS: P = 0.67; Fig. 3A, B). Moreover, we divided the patients into up and down groups based on the alteration in ADC values from pre-nCRT to post-nCRT. The patients with decreased ADC values from pre-nCRT to post-nCRT had a significantly worse OS and DFS (OS: P < 0.01 and DFS: P < 0.01; Fig. 3C, D). These findings highlight the clinical importance of ADC values between pre-nCRT and post-nCRT.

Furthermore, we conducted univariate and multivariate Cox proportional hazard regression analyses to evaluate the prognostic potentials, and patients categorized as low by ADC values in post-nCRT and decreased by alteration-nCRT had a significantly worse OS than patients in high groups (post-nCRT; univariate: hazard ratio [HR] = 5.09, 95% CI = 1.42–18.34, P = 0.01; multivariate: HR = 4.99, 95% CI = 0.97–25.62, P = 0.05 and alteration-nCRT; univariate: HR = 4.52, 95% CI = 1.58–12.97, P < 0.01; multivariate: HR = 6.38, 95% CI = 1.48–27.56, P = 0.01; Table 3). In contrast, patients categorized as low by ADC values in pre-nCRT showed no significant differences in OS (univariate: HR = 1.46, 95% CI = 0.51–4.20, P = 0.49). Among clinicopathological factors, an elevated carbohydrate antigen 19 − 9 (CA19-9) level, low LCR, and high NLR (neutrophil-to-lymphocyte ratio) were associated with a poor OS (CA19-9; univariate: HR = 3.37, 95% CI = 1.05–10.86, P = 0.04; multivariate: HR = 4.34, 95% CI = 0.94–20.11, P = 0.06, LCR; univariate: HR = 5.91, 95% CI = 1.29–27.05, P = 0.02; multivariate: HR = 4.73, 95% CI = 0.93–24.18, P = 0.06; NLR; univariate: HR = 4.16, 95% CI = 1.12–15.52, P = 0.03; multivariate: HR = 1.04, 95% CI = 0.24–4.61, P = 0.96). These results indicate that the alteration in ADC values between pre-nCRT and post-nCRT has prognostic potential in predicting the survival outcomes of patients with LARC.

Table 3

Univariate and multivariate Cox proportional hazard regression analyses for overall survival
	Univariate analysis			Multivariate analysis
Factors	HR	95% CI	p	HR	95% CI	p
Age
(≥ 65 vs. <65 years)	0.82	0.29–2.34	0.71
Gender
(Male vs. Female)	0.69	0.23–2.05	0.50
Tumor size
(≥ 30mm vs. <30mm)	8.16	0.98–68.08	0.05
CEA level
(≥ 5 ng/mL vs. <5 ng/mL)	3.20	0.89–11.51	0.08
CA19-9
(≥ 37 U/mL vs. <37 U/mL)	3.37	1.05–10.86	0.04	4.34	0.94–20.11	0.06
Adjuvant chemotherapy
(Yes vs. No)	1.67	0.51–5.43	0.40
LCR
(Low vs. High)	5.91	1.29–27.05	0.02	4.73	0.93–24.18	0.06
NLR
(High vs. Low)	4.16	1.12–15.52	0.03	1.04	0.24–4.61	0.96
PNI
(Low vs. High)	2.15	0.65–7.14	0.21
TRG
(0,1 vs. 2.3)	1.77	0.59–5.27	0.31
ADC pre-nCRT
(Low vs. High)	1.46	0.51–4.20	0.49
ADC post-nCRT
(Low vs. High)	5.09	1.42–18.34	0.01	4.99	0.97–25.62	0.05
ADC alteration-nCRT
(Down vs. Up)	4.52	1.58–12.97	< 0.01	6.38	1.48–27.56	0.01
ADC, apparent diffusion coefficient; nCRT, neoadjuvant chemoradiotherapy; CA19-9, carbohydrate antigen 19 − 9; CEA, carcinoembryonic antigen; CI: Confidence interval; HR, hazard ration; LCR, lymphocyte to c-reactive protein ratio; NAC, neoadjuvant chemotherapy; NLR, neutrophil-to-lymphocyte ratio; PNI, prognostic nutritional index; SD, standard deviation; TRG, Tumor regression grade

Currently, nCRT followed by radical resection with total mesorectal excision and lymphadenectomy is the standard treatment in LARC (14, 15). nCRT correlated to improved rates of local recurrence, tumor downstaging, and sphincter-preserving surgery and has a favorable toxicity profile in LARC (16). The patients with better responder to neoadjuvant therapy were reported to improve long-term survival outcomes, including OS and DFS (17). The possibilities for predicting therapeutic response and survival outcomes in patients with nCRT may facilitate the administration of individualized cancer-directed treatments (18–21). At present, the evaluation of tumor response after nCRT was performed using clinical staging criteria based on rectal examination, colonoscopy, and MRI. DWI has been examined as an important tool for predicting the tumor responses and accumulating studies suggested that ADC values could be useful as a biomarker for treatment responses in several tumors (22–24). ADC was an imaging biomarker of tumor aggressiveness, and lower ADC values correlated to poor prognosis and more aggressive phenotypes (25).

Additionally, we evaluated the LCR, prognostic nutritional index (PNI), and NLR, which have been suggested to reflect the balance between the anti-tumor immunity and tumor inflammatory status. Accumulating studies indicate that a low nutrition index predicts poor survival and responses to nCRT in patients with LARC (26). In the present study, we showed that an elevated NLR and lower LCR were related to poor survival in patients with LARC, emphasizing the clinical importance of the nutrition index. Therefore, additional studies with more patients are needed to address the potential prognostic value of nutrition indices in LARC.

A good pathological response correlated to prolonged DFS and lower local recurrence rates, and lower distant recurrence rates (27, 28). Recent studies suggested that these patients can be followed closely without surgery (i.e., a “watch and wait” strategy) if complete response can be accurately predicted (18, 20, 29). This could avoid a potential reduction following radical surgery, which harms normal genitourinary and intestinal function (19). In the present study, although the ADC values of pre-nCRT could not be used as a reliable tool to predict survival outcomes, ADC values of post-nCRT correlated to tumor response and survival outcomes. Moreover, the alteration of ADC values from pre-nCRT and post-nCRT were better accuracy for predicting the response and survival outcomes in LARC. The relationship between alteration-nCRT ADC values and tumor responses may allow the selection of patients for a less aggressive surgery or “watch and wait” approach.

Our study has some potential limitations. First, our retrospective and single-institute design might result in a potential selection bias. Thus, a prospective clinical trial is required to further confirm our findings. Second, because we enrolled only patients with ADC values determined pre- and post-nCRT by MRI who underwent nCRT followed by surgery, the present study analyzed a small sample number of patients who received nCRT and radical surgery. Third, the identification of tumor staging was based on CT and MRI modalities, which may have induced an inadvertent bias. It may underestimate or overestimate the tumor, because MRI is known to be a reliable modality for rectal cancer staging.

In conclusion, we revealed the clinical impact of alternations in ADC values determined by MRI for predicting survival outcomes in patients with LARC. Our findings highlight potential clinical strategies to improve the management of patients with this malignancy.

ADC: Apparent diffusion coefficient

AUC: Area under the curve

CA19-9: Carbohydrate antigen 19-9

CEA: Carcinoembryonic antigen

CI: Confidence interval

CT: Computed tomography

DFS: Disease-free survival

DWI: Diffusion-weighted MRI

HR: Hazard ratio

LARC: Locally advanced rectal cancer

LCR: Lymphocyte-to-C-reactive protein ratio

MRI: Magnetic resonance imaging

nCRT: Neoadjuvant chemoradiotherapy

NLR: Neutrophil-to-lymphocyte ratio

OS: Overall survival

PNI: Prognostic nutritional index

ROC: Receiver operator characteristic

ROI: Regions of interest

TRG: Tumor regression grade

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

None of the authors has any potential conflicts to disclose.

Funding

Not applicable.

Authors’ contributions

Y Wada: project development, data collection or management, data analysis, manuscript writing/editing

M Nishi: project development, manuscript writing/editing

K Yoshikawa: data collection or management, manuscript editing

T Tokunaga: data analysis, manuscript editing

T Nakao: data collection or management, manuscript editing

H Kashihara: data analysis, manuscript editing

C Takasu: data analysis, manuscript editing

T Yoshimoto: data analysis, manuscript editing

M Shimada: project development, manuscript editing

Acknowledgment

We thank Dr. Melissa Crawford , PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Liu Z, Zhang XY, Shi YJ, et al.: Radiomics Analysis for Evaluation of Pathological Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer. Clin Cancer Res 23: 7253-7262, 2017.
Siegel RL, Miller KD, Goding Sauer A, et al.: Colorectal cancer statistics, 2020. CA Cancer J Clin 70: 145-164, 2020.
Siegel RL, Miller KD and Jemal A: Cancer statistics, 2020. CA Cancer J Clin 70: 7-30, 2020.
Gérard JP, Conroy T, Bonnetain F, et al.: Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol 24: 4620-4625, 2006.
Kalyan A, Rozelle S and Benson A, 3rd: Neoadjuvant treatment of rectal cancer: where are we now? Gastroenterol Rep (Oxf) 4: 206-209, 2016.
van Gijn W, Marijnen CA, Nagtegaal ID, et al.: Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 12: 575-582, 2011.
Barbaro B, Fiorucci C, Tebala C, et al.: Locally advanced rectal cancer: MR imaging in prediction of response after preoperative chemotherapy and radiation therapy. Radiology 250: 730-739, 2009.
Dzik-Jurasz A, Domenig C, George M, et al.: Diffusion MRI for prediction of response of rectal cancer to chemoradiation. Lancet 360: 307-308, 2002.
Jung SH, Heo SH, Kim JW, et al.: Predicting response to neoadjuvant chemoradiation therapy in locally advanced rectal cancer: diffusion-weighted 3 Tesla MR imaging. J Magn Reson Imaging 35: 110-116, 2012.
Kim YC, Lim JS, Keum KC, et al.: Comparison of diffusion-weighted MRI and MR volumetry in the evaluation of early treatment outcomes after preoperative chemoradiotherapy for locally advanced rectal cancer. J Magn Reson Imaging 34: 570-576, 2011.
Xie H, Sun T, Chen M, et al.: Effectiveness of the apparent diffusion coefficient for predicting the response to chemoradiation therapy in locally advanced rectal cancer: a systematic review and meta-analysis. Medicine (Baltimore) 94: e517, 2015.
Yamada S, Morine Y, Imura S, et al.: Prognostic prediction of apparent diffusion coefficient obtained by diffusion-weighted MRI in mass-forming intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Sci 27: 388-395, 2020.
Yoshikawa M, Morine Y, Yamada S, et al.: Prognostic prediction of resectable colorectal liver metastasis using the apparent diffusion coefficient from diffusion-weighted magnetic resonance imaging. Ann Gastroenterol Surg 5: 252-258, 2021.
Benson AB, Venook AP, Al-Hawary MM, et al.: Rectal Cancer, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 16: 874-901, 2018.
Glynne-Jones R, Wyrwicz L, Tiret E, et al.: Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 29: iv263, 2018.
Sauer R, Becker H, Hohenberger W, et al.: Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351: 1731-1740, 2004.
Jacobs L, Intven M, van Lelyveld N, et al.: Diffusion-weighted MRI for Early Prediction of Treatment Response on Preoperative Chemoradiotherapy for Patients With Locally Advanced Rectal Cancer: A Feasibility Study. Ann Surg 263: 522-528, 2016.
Appelt AL, Pløen J, Harling H, et al.: High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol 16: 919-927, 2015.
Habr-Gama A, Perez RO, Nadalin W, et al.: Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg 240: 711-717; discussion 717-718, 2004.
Maas M, Beets-Tan RG, Lambregts DM, et al.: Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol 29: 4633-4640, 2011.
Renehan AG, Malcomson L, Emsley R, et al.: Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis. Lancet Oncol 17: 174-183, 2016.
Koh DM, Scurr E, Collins D, et al.: Predicting response of colorectal hepatic metastasis: value of pretreatment apparent diffusion coefficients. AJR Am J Roentgenol 188: 1001-1008, 2007.
Niwa T, Ueno M, Ohkawa S, et al.: Advanced pancreatic cancer: the use of the apparent diffusion coefficient to predict response to chemotherapy. Br J Radiol 82: 28-34, 2009.
Patterson DM, Padhani AR and Collins DJ: Technology insight: water diffusion MRI--a potential new biomarker of response to cancer therapy. Nat Clin Pract Oncol 5: 220-233, 2008.
Moon SJ, Cho SH, Kim GC, et al.: Complementary value of pre-treatment apparent diffusion coefficient in rectal cancer for predicting tumor recurrence. Abdom Radiol (NY) 41: 1237-1244, 2016.
Nishi M, Shimada M, Tokunaga T, et al.: Lymphocyte to C-reactive protein ratio predicts long-term outcomes for patients with lower rectal cancer. World J Surg Oncol 19: 201, 2021.
Valentini V, Coco C, Picciocchi A, et al.: Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients. Int J Radiat Oncol Biol Phys 53: 664-674, 2002.
Rödel C, Martus P, Papadoupolos T, et al.: Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 23: 8688-8696, 2005.
Habr-Gama A, Sabbaga J, Gama-Rodrigues J, et al.: Watch and wait approach following extended neoadjuvant chemoradiation for distal rectal cancer: are we getting closer to anal cancer management? Dis Colon Rectum 56: 1109-1117, 2013.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Alteration of apparent diffusion coefficient measurements predict survival outcomes during neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Status:

Version 1

Abstract

Background

Methods

Results

Conclusions

Figures

INTRODUCTION

MATERIALS AND METHODS

Statistical analysis

RESULTS

DISCUSSION

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1