High-Grade Acute Organ Toxicity During Preoperative Radiochemotherapy as Positive Predictor for Complete Histopathologic Tumor Regression in Multimodal Treatment of Locally Advanced Rectal Cancer*

Wolff, Hendrik A.; Gaedcke, Jochen; Jung, Klaus; Hermann, Robert Michael; Rothe, H.; Schirmer, Markus; Liersch, Torsten; Herrmann, Markus K. A.; Hennies, Steffen; Rave-Fränk, Margret; Hess, Clemens F.; Christiansen, Hans

doi:10.1007/s00066-009-2037-1

Cited by 31 publications

(29 citation statements)

References 28 publications

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“…Similarly, Oto et al [15] found that DWI could be used to detect bowel inflammation in patients with Crohn's disease, where the ADC values were significantly lower in inflamed bowel segments than in comparable unaffected regions. Moreover, in a study by Wolff et al [16], pCR has been significantly associated with neoadjuvant CRT that results in acute high-grade organ toxicity, such as proctitis and enteritis, with the authors proposing that both tumour and normal tissue probably behave similarly in response to treatment. Such changes in benign non-cancerous tissue and malignant tissue before and after radiotherapy has been further described in a recent prostate cancer study [17].…”

Section: Discussionmentioning

confidence: 99%

Pathological correlation with diffusion restriction on diffusion-weighted imaging in patients with pathological complete response after neoadjuvant chemoradiation therapy for locally advanced rectal cancer: preliminary results

Jang

Kim

Choi

et al. 2012

BJR

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Objective: The objective of this study was to assess causative pathological factors associated with diffusion restriction on diffusion-weighted imaging (DWI) in patients who achieved pathological complete response (pCR) after treatment with neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer. Methods: In total, 43 patients with locally advanced rectal cancer ($T3 or lymph node positive) who underwent neoadjuvant CRT, subsequent surgery and ultimately achieved pCR were enrolled. All patients underwent pre-and post-CRT 3.0 T rectal MRI with DWI. Two radiologists blinded to pathological staging reviewed pre-and post-CRT 3.0 T rectal MRI for the presence of diffusion restriction in the corresponding tumour areas on post-CRT DWI, with a third radiologist arbitrating any disagreement. The consensus of these findings was then correlated with pathological data such as intramural mucin and the degree of proctitis and mural fibrosis seen on surgical specimen. Additionally, the pre-CRT tumour volume was measured to define the effect of this variable on the degree of radiation proctitis and fibrosis, as well as the presence of intramural mucin. Results: Diffusion restriction occurred in 18 subjects (41.9%), while 25 subjects remained diffusion restriction-free (58.1%). The diffusion restriction group tended to have more severe proctitis and mural fibrosis when compared with non-diffusion restriction group (p,0.001). Intramural mucin was also more common in the diffusion restriction group (p50.052). Higher pre-CRT tumour volumes were significantly predictive of the degree of proctitis (p50.0247) and fibrosis (p50.0445), but not the presence of intramural mucin (p50.0944). Proctitis and mural fibrosis severity were also identified as independent pathological risk factors for diffusion restriction on multivariate analysis (p50.0073 and 0.0011, respectively). Conclusion: Both radiation-induced proctitis and fibrosis were significant and independent predictors of diffusion restriction in patients achieving pCR after treatment with neoadjuvant CRT for locally advanced rectal cancer, and pre-CRT tumour volume significantly affects both variables.

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Section: Discussionmentioning

confidence: 99%

Pathological correlation with diffusion restriction on diffusion-weighted imaging in patients with pathological complete response after neoadjuvant chemoradiation therapy for locally advanced rectal cancer: preliminary results

Jang

Kim

Choi

et al. 2012

BJR

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“…A single case of ileitis requiring discontinuation of therapy near the total dose of radiotherapy occurred. Although it is impossible to exclude TNFerade TM as an explanation for this toxicity, this is a known complication of chemoradiotherapy for rectal cancer [20] .…”

Section: Discussionmentioning

confidence: 99%

A Pilot Feasibility Study of TNFerade™ Biologic with Capecitabine and Radiation Therapy Followed by Surgical Resection for the Treatment of Rectal Cancer

et al. 2010

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Objective: The purpose of this pilot study was to evaluate the feasibility and tolerability of weekly intratumoral TNFerade™ injections combined with concurrent capecitabine and radiotherapy in the treatment of patients with locally advanced rectal cancer. Methods: Patients with T3, T4, or N+ rectal cancer received radiotherapy to a total dose of 50.4–54 Gy in combination with capecitabine 937.5 mg/m2 p.o. b.i.d. TNFerade™ at a dose of 4 × 1010 particle units was injected into the rectal tumor on the first day of radiotherapy and weekly for a total of 5 injections. Surgery was performed 5–10 weeks after the completion of chemoradiation. Results: Nine patients were enrolled in this pilot trial. The stage was cT2 in 2 patients, cT3 in 6 patients, cT4 in 1 patient, N– in 7 patients and N+ in 2 patients. Eight patients completed all treatments. Grade 3 hematologic toxicity was observed in 2 patients. There was no toxicity directly attributable to the injection procedure. A complete pathologic response was observed in 2 of 9 patients. Conclusions: This study demonstrates the feasibility of weekly intratumoral TNFerade™ injections during chemoradiotherapy for locally advanced rectal cancer. Pathologic responses with this combination compare favorably to published rates.

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“…Numerous chemotherapeutic schemes have been tested over the last decade for simultaneous administration with external beam radiotherapy (EBRT), aiming to improve the rates of locoregional control, sphincter-sparing surgery and diminish distant failure [30,33,37]. However, it could not be clarified yet which chemotherapy regimen should be applied in order to achieve the maximal therapeutic benefit for the patient, i.e: an excellent tumour control while providing an acceptable quality of life during and after the treatment [44].…”

Section: Simultaneous Neoadjuvant Radiochemotherapy With Capecitabinementioning

confidence: 99%

Simultaneous neoadjuvant radiochemotherapy with capecitabine and oxaliplatin for locally advanced rectal cancer

Winkler

Zipp

Knoblich³

et al. 2012

Strahlenther Onkol

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High-Grade Acute Organ Toxicity During Preoperative Radiochemotherapy as Positive Predictor for Complete Histopathologic Tumor Regression in Multimodal Treatment of Locally Advanced Rectal Cancer*

Abstract: Acute organ toxicity during preoperative radiochemotherapy in rectal cancer could be an early predictor of treatment response in terms of complete tumor regression. Its possible impact on local control and survival is under further prospective evaluation by the authors' working group.

Cited by 31 publications

References 28 publications

Pathological correlation with diffusion restriction on diffusion-weighted imaging in patients with pathological complete response after neoadjuvant chemoradiation therapy for locally advanced rectal cancer: preliminary results

Pathological correlation with diffusion restriction on diffusion-weighted imaging in patients with pathological complete response after neoadjuvant chemoradiation therapy for locally advanced rectal cancer: preliminary results

A Pilot Feasibility Study of TNFerade™ Biologic with Capecitabine and Radiation Therapy Followed by Surgical Resection for the Treatment of Rectal Cancer

Simultaneous neoadjuvant radiochemotherapy with capecitabine and oxaliplatin for locally advanced rectal cancer

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