Predicting acute small-bowel toxicity in patients with rectal cancer treated with neoadjuvant chemoradiation: A comparison of peritoneal space versus small-bowel loop contouring techniques.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 673-673
Author(s):  
Robyn Banerjee ◽  
Santam Chakraborty ◽  
Ian Nygren ◽  
Richie Sinha

673 Background: In lieu of contouring individual small bowel loops, the peritoneal space (PS) has been suggested as a possible surrogate volume for predicting small bowel toxicity. A dose-volume relationship for the PS has not been firmly established. The aim of this study was to determine whether contours of the PS better predict significant acute small bowel toxicity in neoadjuvant rectal cancer patients when compared with contours of individual small bowel loops. Methods: A standardized contouring method was developed for the PS and retrospectively applied to the radiation treatment plans of sixty-seven patients treated with neoadjuvant chemoradiotherapy for rectal cancer. All patients had locally advanced disease, no evidence of metastases, and received concurrent radiation and infusional 5-Fluorourocil chemotherapy. Dose-volume histogram (DVH) data was extracted and analyzed against patient toxicity. Receiver operating characteristic analysis and logistic regression was carried out for both contouring methods. Results: Grade ≥ 3 small bowel toxicity occurred in 16% (11/67) of patients. Volumes of the contoured small bowel loops correlated with grade ≥ 3 toxicity at each 5 Gray (Gy) dose level from 5 to 45 Gy, with the greatest area under the curve (AUC) measuring .964 (p=.000) associated with the volume receiving at least 25 Gy (V25). Volumes of the contoured PS predicted toxicity from 5 to 40 Gy, with the greatest AUC also at the V25 and measuring .896 (p=.000). Logistic regression analysis demonstrated a less than 15% risk of acute grade ≥ 3 toxicity was associated with a V25 of 215 cc for the small bowel and 710 cc for the PS. Conclusions: DVH analysis of peritoneal space volumes predicts grade ≥ 3 small bowel toxicity in neoadjuvant rectal cancer patients, suggesting the peritoneal space is a reasonable surrogate for contouring individual small bowel loops. However, contouring individual small bowel loops is a more sensitive method for predicting toxicity at each dose increment. For both contouring methods, the greatest sensitivity for predicting toxicity was associated with the volume receiving at least 25 Gy (V25).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15144-e15144 ◽  
Author(s):  
Andrew Wang ◽  
Autumn Jackson McRee ◽  
A. William Blackstock ◽  
Bert H. O'Neil ◽  
Dominic T. Moore ◽  
...  

e15144 Background: There is strong interest in the development of novel agents to further improve the therapeutic ratio of neoadjuvant chemoradiotherapy for rectal cancer. CRLX101 is an investigational nanoparticle-drug conjugate with a camptothecin payload. The purpose of this Phase Ib/II study is to assess toxicity and to evaluate whether the addition of CRLX101 to chemoradiotherapy can improve pathologic complete response (pCR) for rectal cancer. Methods: This is a single-arm multicenter Phase Ib/II study examining the addition of CRLX101 to a standard capecitabine-based chemoradiotherapy regimen. Phase Ib employs a 3+3 dose escalation design with starting dose of 12 mg/m2 every other week (QOW). Dose level +1 was 15 mg/m2 (MTD for CRLX101 single agent QOW). Upon reaching MTD for QOW dosing, protocol was modified to evaluate QW CRLX101 dosing starting at 12 mg/m2 and 15 mg/m2as +1 level. Secondary endpoints included pCR and clinical outcome. Results: A total of 32 patients were enrolled on the trial. 26/32 had T3-4, 9/32 had N2 and 16/32 had N1 disease. For QOW dosing, 9 patients completed treatment without DLT and MTD was identified as 15 mg/m2 QOW. 14 patients were treated on the Phase II portion of the study at 15 mg/m2 QOW prior to the initiation of weekly dosing Phase Ib cohorts. For QW dosing, 0/3 patients experienced DLT at 12 mg/m2 and 1/6 patients experienced DLT at 15 mg/m2. The DLT was skin desquamation requiring treatment delay. QW MTD was identified as 15 mg/m2. Toxicities (all grade 3 except lymphopenia) that could possibly be attributed to CRLX101 are in Table 1. Full clinical and pathologic staging were available for 29/32 patients. Mean neoadjuvant rectal (NAR) score was 19 with standard deviation of 15. At the weekly MTD, 3/6 patients had pCR. Conclusions: CRLX101 weekly at 15 mg/m2+ standard capecitabine-based chemoradiotherapy appears to be well tolerated, with promising pCR rates that warrants further evaluation. A larger PhII trial should be considered with this regimen. Clinical trial information: NCT02010567. [Table: see text]


2020 ◽  
Author(s):  
Siyuan Li ◽  
Yanping Gong ◽  
Yongqiang Yang ◽  
Qi Guo ◽  
Jianjun Qian ◽  
...  

Abstract Background The goal of this study was to assess small bowel motion and explore the feasibility of using peritoneal space (PS) to replace bowel loops (BL) via the dose constraint method to spare the small bowel during intensity-modulated radiotherapy (IMRT) for rectal cancer. Methods A total of 24 patients with rectal cancer who underwent adjuvant radiotherapy were selected. Weekly repeat CT scans from pre-treatment to the fourth week of treatment were acquired and defined as Plan, 1W, 2W, 3W, and 4W. BL and PS contours were delineated in all of the scans. Two IMRT plans called P PS and P BL were designed on Plan CT using two dose PS and BL constraint methods, respectively, and then copied to CT 1~4W. The shift%, dose volume, and NTCP of the small bowel in P PS and P BL during treatment were evaluated. Results Overall, 109 sets of CT scans from 24 patients were acquired, and 218 plans were designed and copied. The PS and BL volumes were 1339.28 cc and 250.27 cc. The BL and PS shift% V 15 was 28.48% and 11.79% ( p =0.000), which was less in the prone position than in the supine position (25.24% vs 32.10%, p =0.000; 9.9% vs 14.85%, p =0.000). On all of the CT scans, most P PS small bowel dose volumes were less than from P BL . V 15 was 170.07 cc vs 178.58 cc ( p =0.000), and they had a significant correlation. The NTCP of chronic and acute side effects from P PS was significantly less than P BL (2.80% vs 3.00%, p =0.018; 57.32% vs 58.64%, p =0.000). Conclusions This study indicated that small bowel motion may lead to uncertainties in its dose volume and NTCP evaluation during IMRT for rectal cancer. The BL movements were significantly greater than PS, and the prone position was significantly less than the supine position. Using PS instead of BL can spare the small bowel. V 15 <830 cc is the dose constraint standard.


2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Huang ◽  
Jun Dang ◽  
Ying Li ◽  
Hai-xia Cui ◽  
Wen-li Lu ◽  
...  

BackgroundWhile chemo-radiotherapy improves local control in patients with locally advanced rectal cancer, it can also increase acute hematological toxicity (HT), which leads to poor outcomes. Patients receiving bone marrow radiation have been shown to develop acute HT. However, the safety and efficacy of bone marrow sparing is undetermined. The aim of our study was to explore the feasible dosimetric constraints for pelvic bone marrow (PBM) that can be widely used in rectal cancer patients undergoing chemo-radiotherapy.Methods112 rectal cancer patients were selected and divided into the PBM sparing IMRT group (60 cases) and the non-PBM sparing IMRT group (52 cases). All patients underwent pelvic radiotherapy with concurrent capecitabine-based chemotherapy. The PBM dosimetric constraints in the PBM sparing IMRT group were set to:V10 ≤ 85%, V20 ≤ 65% and V30 ≤ 45%. An independent sample t test was applied for the dose-volume parameters, and Chi-squared analysis was applied for clinical parameters and adverse events.ResultsThe radiation dose to PBM (V5~V45, Dmean, P&lt;0.05), PBM sub-regions (V10~V35, Dmean, P&lt;0.05) and both femoral heads (V5~V40, Dmean, P&lt;0.05) decreased significantly in the PBM sparing IMRT group compared with that of the non-PBM sparing IMRT group (P&lt;0.05). There was no significant difference in any dose-volume parameters of the bladder and small bowel in either groups, and none in the planning target volume (PTV) dose homogeneity and conformity (P&gt;0.05). For acute HT observation, the incidence of grade 3 acute HT (χ2 = 7.094, P=0.008) was significantly reduced in patients treated with PBM sparing IMRT compared with patients treated with non-PBM sparing IMRT. There was no statistical difference in the incidence of vomiting, diarrhea, fatigue, anorexia, nausea, hand-foot syndrome, cystitis, perianal pain and perianal dermatitis in patients of both groups (P &gt;0.05).ConclusionsApplying PBM dosimetric constraints (V10 ≤ 85%, V20 ≤ 65% and V30 ≤ 45%) can significantly reduce the radiation dose to PBM. The patients treated with PBM sparing IMRT had a lower incidence of acute HT compared with those treated with non-PBM sparing IMRT. Applying the PBM dosimetric constraints proposed by our study can benefits the patients with rectal cancer undergoing capecitabine-based chemo-radiotherapy.


2020 ◽  
Author(s):  
Siyuan Li ◽  
Yanping Gong ◽  
Yongqiang Yang ◽  
Qi Guo ◽  
Jianjun Qian ◽  
...  

Abstract Background The goal of this study was to assess small bowel motion and explore the feasibility of using peritoneal space (PS) to replace bowel loops (BL) via the dose constraint method to spare the small bowel during intensity-modulated radiotherapy (IMRT) for rectal cancer. Methods A total of 24 patients with rectal cancer who underwent adjuvant radiotherapy were selected. Weekly repeat CT scans from pre-treatment to the fourth week of treatment were acquired and defined as Plan, 1W, 2W, 3W, and 4W. BL and PS contours were delineated in all of the scans. Two IMRT plans called PPS and PBL were designed on Plan CT using two dose PS and BL constraint methods, respectively, and then copied to CT 1 ~ 4W. The shift%, dose volume, and NTCP of the small bowel in PPS and PBL during treatment were evaluated. Results Overall, 109 sets of CT scans from 24 patients were acquired, and 218 plans were designed and copied. The PS and BL volumes were 1339.28 cc and 250.27 cc. The BL and PS shift% V15 was 28.48% and 11.79% (p = 0.000), which was less in the prone position than in the supine position (25.24% vs 32.10%, p = 0.000; 9.9% vs 14.85%, p = 0.000). On all of the CT scans, most PPS small bowel dose volumes were less than from PBL. V15 was 170.07 cc vs 178.58 cc (p = 0.000), and they had a significant correlation. The NTCP of chronic and acute side effects from PPS was significantly less than PBL (2.80% vs 3.00%, p = 0.018; 57.32% vs 58.64%, p = 0.000). Conclusions This study indicated that small bowel motion may lead to uncertainties in its dose volume and NTCP evaluation during IMRT for rectal cancer. The BL movements were significantly greater than PS, and the prone position was significantly less than the supine position. Using PS instead of BL can spare the small bowel. V15 < 830 cc is the dose constraint standard.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 504-504
Author(s):  
J. M. Herman ◽  
K. A. Griffith ◽  
A. K. Narang ◽  
M. M. Zalupski ◽  
N. S. Azad ◽  
...  

504 Background: Neoadjuvant conformal chemoradiotherapy (CRT) is an important component of treatment for locally advanced rectal cancer, yet its morbidity has not been well characterized using quality of life (QOL) instruments. The present study attempts to establish a baseline distribution of QOL scores before, during, and after CRT and to correlate these changes with symptoms. Methods: Patients undergoing 3-4 field neoadjuvant CRT for localized rectal cancer were prospectively enrolled at two institutions. Fifty patients completed the QOL instruments at three time points: pretreatment, week 4 of treatment, and 1 month post-treatment. QOL information was captured using three validated questionnaires, the EORTC QLQ-30, QLQ-38, and QLQ-29. Additionally, institutional symptom inventories and CTCAE toxicity data were collected. Results: Average age was 59.2 years and 72% were men. During CRT, patients had a statistically significant decline in global QOL (70 to 60, p = 0.0024), which normalized (71) following completion of treatment. During therapy, patients also experienced a significant increase in GI symptoms (21 to 27, p = 0.028), urinary symptoms (16 to 30, p < 0.0001), male sexual dysfunction (23 to 34, p = 0.013), and chemotherapy related side effects (8 to 20, p = 0.0001). While these measures returned to baseline 1 month post-CRT, overall sexual function (25 vs. 37, p = 0.0062) and sexual enjoyment (53 vs. 67, p = 0.0070) remained persistently low compared to pretreatment levels. Diarrhea (27%) and proctitis (22%) were the most common grade 3 toxicities. Those patients who experienced grade 3 toxicity during treatment showed markedly decreased global QOL (mean difference = 34). Conclusions: While rectal cancer patients experienced impaired QOL during neoadjuvant CRT, the vast majority of measures normalized one month after treatment. In contrast, significantly decreased sexual function and enjoyment persisted. This data can be used as a baseline to compare future neoadjuvant conformal CRT regimens and/or assess the toxicity and QOL of new RT modalities such as intensity modulated radiation therapy. No significant financial relationships to disclose.


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