The split scar sign as an indicator of sustained complete response after neoadjuvant therapy in rectal cancer
Inês Santiago, Maria Barata, Nuno Figueiredo, Oriol Parés, Vanessa Henriques, António Galzerano, Carlos Carvalho, Celso Matos, Richard J. Heald.
Eur Radiology 2020 Jan;30(1):224-238. doi: 10.1007/s00330-019-06348-9
Total mesorectal excision (TME) is nowadays a standard surgery for rectal cancer, that showed significant increase in 5-year survival and decrease in local recurrence.[1]
Moreover, clinical trials and guidelines support the use of neoadjuvant radiation for further oncologic improvement in high-risk patients.[2] It was shown that up to 15–27% of patients who underwent preoperative chemoradiation had no residual viable tumor cells detected in the resected specimen.[3,4]
The studies demonstrated similar outcomes in those patients who later underwent surgery and those who were managed with “watch and wait protocol”, avoiding significant morbidity and mortality risks associated with TME in a second group.[5]
Watchful waiting is now an established policy in many colorectal centers worldwide. This strategy requires close surveillance protocols for early detection of regrowth, including both imaging studies and colonoscopy. MRI is playing a fundamental role in assessing rectal wall and mesorectum before, during and after treatment. During the last decade, MRI response assessment is mainly based on tumor regression grade, evaluating intermediate residual tumor signal and low fibrosis signal on T2 weighted imaging6, and diffusion weighted imaging, that improves accuracy, but still depends on reader’s experience and quality of the image.
Inês Santiago and co-authors reported a new radiologic pattern of sustained complete response, that they called “split scar sign” (mrSSS), evaluated on high resolution T2-weighted images, and measured its diagnostic performance. This new pattern, according to the authors, is easy to assess and has a high specificity and PPV.
This is a retrospective study that enrolls fifty-eight patients who underwent neoadjuvant therapy for rectal adenocarcinoma in their institution between 1/10/2012 and 1/3/2017.
Patients’ demographics and clinical data was collected by physician uninvolved in imaging reading. Rectal MRI images were blindly and independently analyzed by two gastrointestinal radiologists, with 12 and 10 years of experience, respectively. Observers performed initial rectal cancer staging and later analyzed post neoadjuvant pelvic MR, acquired with a mean interval of 9.1 weeks after the end of radiotherapy.
On the first round: the presence of the split scar sign (mrSSS+) -a radiologic sign observed on T2-WI and characterized by a particular morphologic pattern of the tumor scar- was considered indicative of a sustained clinical response (SCR). It is characterized by the presence of an inner, markedly T2-hypointense, regular layer of tissue at tumor location, corresponding to the fibrosed submucosa, covered by normal mucosa, or denuded when ulceration is present; and a homogeneous intermediate signal intensity layer underneath it, corresponding to a markedly thickened and partially fibrotic muscularis propria. At the periphery, a T2-hypointense layer of variable regularity and thickness is usually apparent, translating perirectal fibrosis. It may, however, be absent, particularly in early-staged tumors. In mucinous tumors or tumors which respond with mucinous degeneration, the intermediate signal intensity may be replaced with high signal intensity, corresponding to mucin pooling. Vessels may pierce the outer hypointense layer in positive cases. On the other hand, the split scar sign is considered absent (mr SSS-) when the inner or the outer hypointense layer (when present) are bulged or breached by intermediate signal intensity, either the scar is completely hypointense or heterogeneous, with a “disorganized” appearance.
On a second round the authors assessed the relative proportion of intermediate signal intensity on T2-WI (mrT2), and of high signal intensity on high b-value diffusion-weighted imaging (mrDWI), separately and without taking into consideration morphologic pattern of the scar.
Endoscopy was performed upon patient restaging and tumor p stage was retrieved from the pathology reports in operated patients.
The reference standard was SCR, defined as pathologic complete response or long-term local recurrence-free clinical follow-up (minimum follow-up period of 1 year).
Qui-square test was employed in search for associations between SCR and mrSSS, mrT2, mrDWI and endoscopy. Interobserver agreement for imaging parameters was estimated using Cohen’s kappa (k).
The obtained results were the following: mrSSS was significantly associated with SCR, with specificity= 0.97/0.97, sensitivity= 0.52/0.64, PPV= 0.93/0.94, NPV= 0.73/0.78, and AuROC= 0.78/0.83 for observers 1/2, respectively. According to their results, the authors divided all patients in two main groups: mr SSS+ patients have a 97% chance of achieving a SCR, and those with mr SSS- have a 73–78% chance of failing to do so.
Despite some limitations (e.g., retrospective nature, cases from one institution, absence of lymph-node assessment, the time interval between the end of chemoradiation and MR imaging, minimal follow-up of one year, and a type of radiotherapy applied in their institution), this study demonstrated that split scar sign, though not sensitive, is very specific morphologic pattern for the identification of sustained complete responders after neoadjuvant therapy in rectal cancer.
Observers that mrSSS has even higher specificity than combined morphologic and functional visual pattern approach, based on T2-WI and DWI: 94% vs 77% respectively [7].
This morphologic pattern is state of art in rectal cancer response, already widely accepted by GI radiologists and appearing with increasing frequency in the scientific presentations of ESGAR. I encourage GI radiologists to apply it routinely, not only for improvement in patient selection for “watch-and-wait” after neoadjuvant therapy, but also for surgery planification after radiation in low rectal cancer, for example, evaluating external sphincter possible preservation in selected patients.
References:
- Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet. 1986 Jun 28;1(8496):1479-82. doi: 10.1016/s0140-6736(86)91510-2. PMID: 2425199.
- Glimelius B, Tiret E, Cervantes A, Arnold D; ESMO Guidelines Working Group. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up. Ann Oncol. 2013 Oct;24 Suppl 6:vi81-8. doi: 10.1093/annonc/mdt240. PMID: 24078665.
- Janjan NA, Khoo VS, Abbruzzese J, et al. Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys 1999; 44: 1027–38.
- Pucciarelli S, Toppan P, Friso ML, et al. Complete pathologic response following preoperative chemoradiation therapy for middle to lower rectal cancer is not a prognostic factor for a better outcome. Dis Colon Rectum 2004; 47: 1798–807.
- Dossa F, Chesney TR, Acuna SA, Baxter NN. A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2017 Jul;2(7):501-513. doi: 10.1016/S2468-1253(17)30074-2. Epub 2017 May 4. PMID: 28479372.
- Patel UB, Taylor F, Blomqvist L, George C, Evans H, Tekkis P, Quirke P, Sebag-Montefiore D, Moran B, Heald R, Guthrie A, Bees N, Swift I, Pennert K, Brown G. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. J Clin Oncol. 2011 Oct 1;29(28):3753-60. doi: 10.1200/JCO.2011.34.9068. Epub 2011 Aug 29. PMID: 21876084.
- Lambregts DMJ, Delli Pizzi A, Lahaye MJ, van Griethuysen JJM, Maas M, Beets GL, Bakers FCH, Beets-Tan RGH. A Pattern-Based Approach Combining Tumor Morphology on MRI With Distinct Signal Patterns on Diffusion-Weighted Imaging to Assess Response of Rectal Tumors After Chemoradiotherapy. Dis Colon Rectum. 2018 Mar;61(3):328-337. doi: 10.1097/DCR.0000000000000915. PMID: 29369900.
Polina Rudenko is a young consulting gastrointestinal radiologist from La Fe University Hospital (Valencia, Spain) mainly specializing in colorectal cancer and inflammatory bowel disease. She is an active ESGAR member since 2015.
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