One of the main criticisms of NOM in patients with LARC is the poor correlation between cCR (based on both clinical examination and imaging studies) and pCR to neoadjuvant therapy. However, response has typically been assessed a few weeks after completion of neoadjuvant therapy, before some tumors have achieved maximal response, and before treatment-related tissue changes have had an opportunity to subside. This will be the first study to investigate the accuracy of clinical examination and imaging studies in assessing tumor response after a much longer treatment interval. It will also help validate a set of predefined criteria regarding clinical and radiological response(see Table 2).
Additionally, we will evaluate the feasibility of using circulating tumor DNA and miRNA profiles in plasma, to monitor tumor response to TNT, in rectal cancer patients treated in both of the protocol arms. Genomic analysis by next-generation sequencing will be done to profile rectal cancer treated with neoadjuvant chemotherapy and radiation. The separation of responders from non-responders will facilitate investigation of the molecular mechanisms of tumor resistance to neoadjuvant therapy through genomic analysis of rectal cancer before and after treatment. We think that this will lead to more precise treatments of individual rectal cancer patients based on the molecular profile associated with each individual tumor.
In summary, this study will not only explore the feasibility of NOM in a selected group of patients with LARC who respond to neoadjuvant therapy. It will also provide a wealth of information about the response of LARC to chemotherapy and radiation. By delivering all adjuvant therapy up front, we will be able to discriminate (or separate) responders from non-responders, determining the real proportion of patients who will benefit from NOM, facilitating the clinical and radiological identification of responders, and facilitating molecular profiling. Finally, the study will help determine the gains in QoL associated with descargar IHeartBreaker organ preservation.
Delivery of chemotherapy before rather than after surgery will improve survival, because it will treat microscopic tumor deposits several months earlier, will increase the proportion of patients completing the entire treatment, and may reduce the size of the primary tumor. This study will compare the two different TNT regimens in two randomized treatment arms. One treatment arm will receive systemic chemotherapy before chemoradiation, and the other treatment arm will receive it after chemoradiation.
Delivery of chemotherapy before rather than after surgery will shorten the amount of time before ileostomy reversal. This study investigates the feasibility and efficacy of delivering all adjuvant treatment before surgery in LARC patients. Some previous phase II trials have investigated the use of chemotherapy before surgery in such patients, but the chemotherapy delivered in these trials was only a portion of that normally used after surgery. In this study, we deliver all chemotherapy before surgery (TNT). The results could be confirmed in a phase III trial, and may represent the groundwork for a paradigm shift in the treatment of rectal cancer.
Avoiding surgery selectively in patients with tumors that respond to CRT will reduce over-treatment and improve quality of life. The underlying theme here is individualized treatment, tailored in a more precise fashion. The potential gains for these patients in terms of improved QoL will be significant. Over 20,000 new stage II and III rectal cancers are diagnosed in the United States every year. Assuming a 30 % rate of complete response, this could mean that 6,000 patients will benefit from NOM, leading to significant economic benefits and better QoL.
Patient selection and eligibility criteria
Near-complete response. Endoscopic and T2-weighted MRI images both pre- and post-treatment are shown for a patient who has achieved a near complete response. This is a 74-year-old man who underwent 8 cycles of induction FOLFOX followed by CRT, and achieved a near-cCR. A biopsy obtained in surveillance was determined to contain residual cancer; therefore, the patient was referred for TME
Discussion
Patients with distal rectal cancer who require a CAA as part of their surgical treatment also have a temporary diverting loop ileostomy to reduce the risk of pelvic sepsis. Patients treated according to the standard protocol of CRT, TME and ACT must live with a diverting loop ileostomy for many months until they complete postoperative adjuvant chemotherapy. While the ileostomy is effective in reducing major pelvic infections, it is an inconvenience to the patient; it is also the source of complications, such as dehydration and electrolyte imbalances, which often require readmission to hospital . Delivering all systemic chemotherapy in the neoadjuvant setting will shorten ileostomy time.