The Impact of Pathologic Complete Response in Patients with Neoadjuvantly Treated Locally Advanced Rectal Cancer—a Large Single-Center Experience

Dinaux, Anne M.; Amri, Ramzi; Bordeianou, Liliana; Hong, Theodore S.; Wo, Jennifer Y.; Blaszkowsky, Lawrence S.; Allen, Jill N.; Murphy, Janet E.; Kunitake, Hiroko; Berger, David L.

doi:10.1007/s11605-017-3408-z

Cited by 23 publications

(16 citation statements)

References 25 publications

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“…In various studies pCR determined a long-term survival (LTS), was associated with lower incidence of local and distant recurrence, as well as resulted in favorable progressive-free survival (PFS) (1). Similar prognostic significance of pCR has been reported in esophageal, rectal, breast and bladder cancer (2)(3)(4)(5)(6). Irrespective its prognostic significance, the implication of pCR in daily practice is limited, due to inaccurate nonoperative evaluation of the tumor response, wide pCR variability depending on treatment protocol and therefore, unpredictable incidence of pCR (7).…”

Section: Introductionmentioning

confidence: 77%

Pathologic complete response after induction therapy—the role of surgery in stage IIIA/B locally advanced non-small cell lung cancer

et al. 2018

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Section: Introductionmentioning

confidence: 77%

Pathologic complete response after induction therapy—the role of surgery in stage IIIA/B locally advanced non-small cell lung cancer

et al. 2018

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“…As a result of the low compliance and high complication rates observed with adjuvant chemotherapy, recent shifts toward a total neoadjuvant approach, where neoadjuvant instead of adjuvant chemotherapy is administered in an attempt to increase the pCR rate, which is of major prognostic impact in rectal cancer [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced rectal adenocarcinoma

et al. 2020

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Background Current standard practice for locally advanced rectal cancer (LARC) entails a multidisciplinary approach that includes preoperative chemoradiotherapy, followed by total mesorectal excision, and then adjuvant chemotherapy. The latter has been accompanied by low compliance rates and no survival benefit in phase III randomized trials, so the strategy of administering neoadjuvant, rather than adjuvant, chemotherapy has been adapted by many trials, with improvement in pathologic complete response. Induction chemotherapy with oxaliplatin has been shown to have increased efficacy in rectal cancer, while short-course radiation therapy with consolidation chemotherapy increased short-term overall survival rate and decreased toxicity levels, making it cheaper and more convenient than long-course radiation therapy. This led to recognition of total neoadjuvant therapy as a valid treatment approach in many guidelines despite limited available survival data. With the upregulation (PDL-1) expression in rectal tumors after radiotherapy and the increased use of in malignant melanoma, the novel approach of combining immunotherapy with chemotherapy after radiation may have a role in further increasing pCR and improving overall outcomes in rectal cancer. Methods The study is an open label single arm multi- center phase II trial. Forty-four recruited LARC patients will receive 5Gy x 5fractions of SCRT, followed by 6 cycles of mFOLFOX-6 plus avelumab, before TME is performed. The hypothesis is that the addition of avelumab to mFOLFOX-6, administered following SCRT, will improve pCR and overall outcomes. The primary outcome measure is the proportion of patients who achieve a pCR, defined as no viable tumor cells on the excised specimen. Secondary objectives are to evaluate 3-year progression-free survival, tumor response to treatment (tumor regression grades 0 & 1), density of tumor-infiltrating lymphocytes, correlation of baseline Immunoscore with pCR rates and changes in PD-L1 expression. Discussion Recent studies show an increase in PD-L1 expression and density of CD8+ TILs after CRT in rectal cancer patients, implying a potential role for combinatory strategies using PD-L1- and programmed-death- 1 inhibiting drugs. We aim through this study to evaluate pCR following SCRT, followed by mFOLFOX-6 with avelumab, and then TME procedure in patients with LARC. Trial registration Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT03503630, April 20, 2018.

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“…Data from a randomized clinical trial performed in 2004 showed that TME preceded by chemoradiation was safer and more effective than TME with no prior treatment in patients with LARC [ 6 – 8 ]. NACRT improves the local control of the malignancy and overall survival, particularly in patients with a complete response to treatment [ 9 , 10 ]. However, in Europe and the USA, ~ 50% of patients do not receive this treatment, primarily owing to advanced age and comorbidities [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

The prognostic impact of neoadjuvant chemoradiotherapy on lymph node sampling in patients with locally advanced rectal cancer

Maugeri

Ramistella

et al. 2020

Updates Surg

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According to the American Joint Committee on Cancer, at least 12 lymph nodes are required to accurately stage locally advanced rectal cancer (LARC). Neoadjuvant chemoradiation therapy (NACRT) reduces the number of lymph nodes retrieved during surgery. In this study, we evaluated the effect of NACRT on lymph node retrieval and prognosis in patients with LARC. We performed an observational study of 142 patients with LARC. Although our analysis was retrospective, data were collected prospectively. Half the patients were treated with NACRT and total mesorectal excision (TME) and the other half underwent TME only. The number of lymph nodes retrieved and the number of metastatic lymph nodes were significantly reduced in the NACRT group (P > 0.001). In the univariate and multivariate analyses, only NACRT and patient age were significantly associated with reduced lymph node retrieval. The number of metastatic lymph nodes and the lymph node ratio (LNR) both had a significant effect on prognosis when the patient population was examined as a whole (P = 0.003 and P = 0.001, respectively). However, the LNR was the only significant, independent prognostic factor in both treatment groups (P = 0.007 for the NACRT group; P = 0.04 for the no-NACRT group). NACRT improves patient prognosis only when the number of metastatic lymph nodes is reduced. The number of metastatic lymph nodes and the LNR are important prognostic factors. Lymph node retrieval remains an indispensable tool for staging and prognostic assessment of patients with rectal carcinoma treated with NACRT.

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The Impact of Pathologic Complete Response in Patients with Neoadjuvantly Treated Locally Advanced Rectal Cancer—a Large Single-Center Experience

Cited by 23 publications

References 25 publications

Pathologic complete response after induction therapy—the role of surgery in stage IIIA/B locally advanced non-small cell lung cancer

Pathologic complete response after induction therapy—the role of surgery in stage IIIA/B locally advanced non-small cell lung cancer

Short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced rectal adenocarcinoma

The prognostic impact of neoadjuvant chemoradiotherapy on lymph node sampling in patients with locally advanced rectal cancer

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