Introduction

Locally advanced rectal cancer (LARC) poses a significantly challenge in clinical management, involving multimodal treatment approach. Among innovative strategies, Total Neoadjuvant Therapy (TNT) has emerged, delivering all planned chemotherapy before surgery.

Aims & Methods

Our aim was to evaluate the real-world application and efficacy of TNT and to compare it with non-TNT strategy.
This retrospective study compared 107 locally advanced rectal adenocarcinoma patients treated with Total Neoadjuvant Therapy (TNT) from 2022 and traditional chemoradiotherapy (CRT) from 2020-2021. Evaluation included primary endpoints of efficacy, tolerability, and completion rates.

Results

Among 107 patients (54.2% male, mean age 62.48 years), non-TNT and TNT follow-ups were 26.66 and 8.19 months, respectively. No differences in gender(p=0.163), staging (p=0.707), or location (p=0.727) were noted. TNT patients received more short-course radiotherapy (42.5% vs1.5%, p<0.001). Clinical responses favored TNT (p= 0.030) with no significant differences in pathological responses, recurrence rates, or survival. TNT exhibited higher chemotherapy completion (p = 0.007) and lower adverse events (p<0.001). Post-surgery events showed no significant differences (p=0.470).

Conclusion

In conclusion, our data add to the body of literature favoring the TNT treatment strategy for locally advanced rectal cancer, aiming to achieve higher complete response rates with less adverse events.

References

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID: 33538338.
2. Oronsky B, Reid T, Larson C, Knox SJ. Locally advanced rectal cancer: The past, present, and future. Semin Oncol. 2020 Feb;47(1):85-92. doi: 10.1053/j.seminoncol.2020.02.001. Epub 2020 Feb 21. PMID: 32147127.
3. Maas M, Beets-Tan RG, Lambregts DM, Lammering G, Nelemans PJ, Engelen SM, van Dam RM, Jansen RL, Sosef M, Leijtens JW, Hulsewé KW, Buijsen J, Beets GL. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011 Dec 10;29(35):4633-40. doi: 10.1200/JCO.2011.37.7176. Epub 2011 Nov 7. PMID: 22067400.

Introduction

The treatment of rectal cancer (RC) has been evolving in recent decades, aiming at improving organ preservation. This work evaluates the results of the Watch & Wait (W&W) strategy in a tertiary cancer centre.

Aims & Methods

Patients diagnosed with adenocarcinoma of the rectum up to 6cm from the anal margin, cM0, >cT1N0, with diagnosis and first multidisciplinary consultation between June 2014 and June 2020 were included. All patients received neoadjuvant radiotherapy ± chemotherapy and underwent reassessment at 8-12 weeks. Patients with complete clinical response (cCR), defined by proctological examination, fibrosigmoidoscopy and magnetic resonance imaging, initiated surveillance in the W&W protocol and the other were offered surgery. We present the follow-up of patients until December 2023.

Results

The study included 137 patients, 56% male, mean age 63.7 ±15 years. Stage at diagnosis: III (75%), II (13%) and I (12%). After neoadjuvant treatment, 18 patients (13.6%) had a complete response. Stage I at diagnosis was associated with a higher probability of achieving cCR (p=0.008). All patients without CRC (113) underwent surgery: 50.4% abdominoperineal resection and 40.7% anterior resection of the rectum. The operative specimen revealed N+ disease in 23.7% of patients and complete pathological response in 14. Median follow-up time of 44 months ± 26 (3.6 years).
In the W&W group, 6/18 patients presented regrowth, between 3 and 35 months (mean at 15.8 months), 4 were treated with surgery (2 refused), 1 of 4 had local recurrence after surgery). None of the patients had distant disease. At the end of follow-up, 15 patients were alive without disease, 2 alive with disease, and 1 died from disease.
Of the remaining 113 patients: 28 (26.4%) patients showed distant recurrence and 3 patients local and distant relapse. At the end of follow-up, 70 (62%) of patients (62 had no disease, 7 had disease, 1 was unknown) and 11.4% had death attributed to disease.

Comparing the two approaches, there is no difference between local recurrence, but there is a higher probability of distant recurrence by the traditional approach (p<0.009) as well as death (p=0.006).
When comparing patients under WW approach with patients with complete pathological response after traditional approach, there was only a higher probability of local recurrence in WW (0.011), with no statistically significant differences in distant recurrence or mortality.

Conclusion

In this cohort, with a longer follow-up period, the W&W approach continues to be a safe oncological approach, as described internationally.

References

López-Campos F, Martín-Martín M, Fornell-Pérez R, García-Pérez JC, Die-Trill J, Fuentes-Mateos R, López-Durán S, Domínguez-Rullán J, Ferreiro R, Riquelme-Oliveira A, Hervás-Morón A, Couñago F. Watch and wait approach in rectal cancer: Current controversies and future directions. World J Gastroenterol. 2020 Aug 7;26(29):4218-4239. doi: 10.3748/wjg.v26.i29.4218. PMID: 32848330; PMCID: PMC7422545.

Introduction

Radiation therapy as part of neoadjuvant treatment for rectal cancer aims to improve local disease control with increased response rates and the possibility of sphincter preservation. The addition of the "watch and wait" (W&W) strategy has increased the efficacy and safety associated with neoadjuvant radiotherapy. Despite the use of low doses (between 40-50.4 Gy), most studies report complete pathological response rates of 10-27%. However, there is still a lack of studies with higher doses to evaluate effectiveness in terms of clinical and pathological response, versus the toxicity associated with increased radiation dose.

Aims & Methods

The aim was to evaluate the efficacy and tolerance of neoadjuvant therapy for potentially resectable rectal cancer with higher radiation doses.
A retrospective observational preliminary study included 41 individuals with potentially resectable rectal cancer (T2-T4, N0-1, M0), treated with capecitabine (825mg/m2 every 12 hours, 5 days a week) and 25 sessions of 54 Gy + 50 Gy to pelvic lymph nodes, considering patients on W&W. Partial response was defined as downstaging of at least 1 level in T and/or N. Complete clinical response was defined as reevaluation by MRI, endoscopy with biopsies, and digital rectal examination without evidence of residual disease. Short- and long-term complications of increased radiation dose were also evaluated.

Results

Out of 41 individuals with potentially resectable disease observed during the study, downstaging was observed in 78% (n=32), with 29% (n=12) showing complete response (clinical and/or pathological). Of the patients with complete clinical response (n=12), 8 underwent total mesorectal excision due to unpassable stenosis affecting adequate visualization of the rectal mucosa (n=1), presence of rectal ulcer with negative biopsies (n=6), and concurrent ulcerative colitis (n=1). All these patients showed complete pathological response. Four patients entered the W&W protocol, 3 of them with residual ulcer and negative biopsies, without recurrence at present (4 years follow-up). Radiation therapy complications were observed in 7% (n=3) of patients, respectively due to rectal stenosis, radiation proctitis, and radiation cystitis.

Conclusion

Our study found higher rates of downstaging and complete response compared to most studies under similar conditions and with lower radiotherapy doses, with a relatively low frequency of adverse effects.

References

Anter, A., Eladawei, G., & Mosbah, M. (2013). Preoperative capecitabine and pelvic radiation in locally advanced rectal cancer: preliminary results (Mansoura experience). Translational Gastrointestinal Cancer, 2(3), 112-117.
Korkolis, D. P., Boskos, C. S., Plataniotis, G. D., Gontikakis, E., Karaitianos, I. J., Avgerinos, K., Katopodi, A., Xinopoulos, D., Dimitroulopoulos, D., Beroukas, K., & Vassilopoulos, P. P. (2007). Pre-operative chemoradiotherapy with oral capecitabine in locally advanced, resectable rectal cancer. Anticancer research, 27(1B), 541–545.
A. De Paoli, et al. (2006). Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study, Annals of Oncology, Volume 17, Issue 2, Pages 246-251,

Introduction

Watch-and-Wait is an increasingly recognized non-surgical management option for rectal cancer patients achieving a clinical complete response (cCR) following neoadjuvant therapy. This approach aims to preserve organ function by avoiding surgery, but necessitates vigilant endoscopic surveillance, to detect local tumor regrowth¹ (LTR). The specific endoscopic features associated with regrowth remain incompletely defined.

Aims & Methods

We performed a retrospective analysis of patients monitored under the Watch-and-Wait program at Karolinska University Hospital², focusing on the endoscopic characteristics of LTR. As of December 2023, 145 patients who met the criteria for clinical complete response (cCR) were included.
The neoadjuvant treatment consisted of chemoradiotherapy (CRT) in 16 patients (11%), short course radiotherapy (SCRT) + chemotherapy in 69 patients (47.6%) and SCRT alone (5 x 5 Gy) in 60 patients (41.4%). The median age of the patients was 66 years (range 29-94), with 61.4% being male. The initial tumor stage was T1/T2 in 42 patients (29%) and T3/T4 in 103 patients (71%). The nodal stage was N0 in 35 patients (24%) and N+ in 110 patients (75.9%). The median follow-up period was 29 months (range 3-102 months).
Patients were monitored with rectal digital exams, flexible endoscopy, CEA measurements, and MRI every 3 months for 2 years, and then every 6 months thereafter. During endoscopy, narrow-band imaging (NBI) and NICE classification³ was utilized.

Results

Out of the 145 patients, 28 (19.3%) experienced LTR as of December 2023. The median time from the completion of radiotherapy to regrowth was 9 months (range 3-20 months). Regrowth was detected intraluminally by endoscopy in 23 patients (82.1%), while in 5 patients (17.9%), regrowth was detected on MRI but was not visible intraluminally.
The most common endoscopic features of regrowth included a NICE 3 pattern (n=16) and contact bleeding (n=16). Additional findings included polypoid tissue (n=13), ulceration (n=10), irregular surface (n=9), fibrin cover (n=9), stenosis (n=6), and submucosal nodules (n=5).

Conclusion

As regrowth occurs in at least one of five patients and most commonly with intraluminal findings, this study highlights the importance of meticulous endoscopic follow-up. Contact bleeding and NICE type 3 lesions observed with narrow-band imaging (NBI) were key endoscopic findings in patients with tumor regrowth, while polypoid lesions were observed in less than 50%. Combining endoscopic assessment with other modalities, such as MRI, is essential, as regrowth may be undetectable endoscopically in a proportion of patients.

References

1. Cerdan-Santacruz C, Vailati BB, Sao Juliao GP, Habr-Gama A, Perez RO. Local tumor regrowth after clinical complete response following neoadjuvant therapy for rectal cancer: what happens when organ preservation falls short. Tech Coloproctol 2023;27(1):1-9. DOI: 10.1007/s10151-022-02654-5.
2. Nilsson PJ, Ahlberg M, Kordnejad S, Holm T, Martling A. Organ preservation following short-course radiotherapy for rectal cancer. BJS Open 2021;5(5). DOI: 10.1093/bjsopen/zrab093.
3. Hamada Y, Tanaka K, Katsurahara M, et al. Utility of the narrow-band imaging international colorectal endoscopic classification for optical diagnosis of colorectal polyp histology in clinical practice: a retrospective study. BMC Gastroenterol 2021;21(1):336. DOI: 10.1186/s12876-021-01898-z.

Disclosure

Stephan Haas (SLH) has received speaker's honoraria from Santax Medico, Tillotts Pharma, Lilly, Mediahuset, and Johnson & Johnson.

Introduction

There are two approaches for neoadjuvant treatment in locally advanced rectal cancer: conventional radiotherapy (RT) with concomitant chemotherapy and hypofractionated RT. In the RAPIDO study, preoperative hypofractionated RT versus conventional chemo-radiotherapy was proven to be equally effective. In our country and in our center (approximately 90%) previously, the standard treatment was conventional RT, however due to the COVID 19 pandemic in 2020, an increase in the use of hypofractionated RT was observed, this because it was a more accessible therapy for patients due to visits. In our country, the results of hypofractionation therapy compared to a conventional one have not been explored, therefore we decided to compare the outcomes between these modalities.

Aims & Methods

To compare early radiotoxicity of conventional vs. hypofractionated RT.
Methods: Retrospective study conducted in a national reference cancer center at National Institute of Cancer (INCAN) at Mexico City, during the period of April 2020 to December 2020.

Results

We analyzed 61 patients with rectal adenocarcinoma. Locally advanced were 91.8% and metastatic 8.2%. By tumor location upper third 11.4%, middle third 16.4%, middle third 72.1%. Regarding treatment, 72.1% received hypofractionation (25Gy in 5 fractions) and 27.9% conventional (45-50.4 Gy in 25-28 fractions). Techniques used 93.4% 3DCRT, 4.9% IMRT and 1.6% VMAT. Regarding general toxicity, it was observed in 30 patients (68%) in the hypofractionated group and 11 patients (64%) in the conventional treatment group p=0.794. Type of radiotoxicity is described in table 1. We observed a greater radiation mucositis grade 3 in the hypofractionated group compared with standard therapy. The other types were similar with no statistical significance. Table 1.

Conclusion

We observed a considerable increase in the use of hypofractionation in which we did not observe proctitis and cystitis in relation to conventional treatment, however caution and special attention must be exercised in radiation mucositis. We can increase the use of hypofractionated treatment with almost similar radiotoxicities. Further prospective studies are required to confirm these findings.

References