Complete neoadjuvant treatment for rectal cancer: A single institution experience.

148 Background: Full dose adjuvant chemotherapy following preoperative chemoradiation and surgery is poorly tolerated in stage II and III rectal cancer. We reviewed our institution’s experience with complete neoadjuvant treatment for rectal cancer since publication of the BrUOG R-224 trial results. Methods: After obtaining IRB approval, Data on patients with stage II and III rectal cancer who underwent complete neoadjuvant therapy were collected.. Patients who were planned to receive 8 cycles of modified FOLFOX6, chemoradiation with capecitabine 825 mg/m2 twice daily and 50.4 Gy intensity-modulated radiation therapy, then surgery were included. Results: Thirty-five patients were treated with complete neoadjuvant therapy between January 2014 and December 2017. Median age was 58 years (27 to 75 y); 1 patient (3%) was clinical stage II and 34 (97%) stage III. Twenty-seven patients (77%) received all 8 cycles of mFOLFOX6, of whom 24 completed subsequent chemoradiation. Therefore 69% of patients completed therapy according to the BrUOG R-224 protocol. Pathologic complete response (ypT0N0) was observed in 9 patients (26%). Treatment related toxicities resulted in dose reductions or treatment interruption in 57% and 29% of patients receiving chemotherapy and chemoradiation respectively. Conclusions: Complete neoadjuvant therapy for clinical stage II to III rectal cancer is well-tolerated in routine practice and offers an alternative to preoperative chemoradiation, surgery, then adjuvant full dose chemotherapy.

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908 TOTAL NEOADJUVANT THERAPY VERSUS NEOADJUVANTCHEMORADIATION IN PATIENTS WITH STAGE II-III RECTAL CANCER: IMPACT ON PATHOLOGIC COMPLETE RESPONSE, TUMOR DOWNSTAGING, AND SURVIVAL RATES.

Gastroenterology ◽

10.1016/s0016-5085(20)34533-9 ◽

2020 ◽

Vol 158 (6) ◽

pp. S-1542

Author(s):

Paolo Goffredo ◽

Adil Khan ◽

Sarah Bell ◽

Xiang Gao ◽

Kyle Freischlag ◽

...

Keyword(s):

Rectal Cancer ◽

Neoadjuvant Therapy ◽

Survival Rates ◽

Pathologic Complete Response ◽

Complete Response ◽

Stage Ii ◽

Tumor Downstaging ◽

Total Neoadjuvant Therapy

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Organ preservation in patients with rectal cancer with clinical complete response after neoadjuvant therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.509 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 509-509 ◽

Cited By ~ 20

Author(s):

Jesse Joshua Smith ◽

Oliver S Chow ◽

Anne Eaton ◽

Maria Widmar ◽

Garrett Michael Nash ◽

...

Keyword(s):

Rectal Cancer ◽

Neoadjuvant Therapy ◽

Pathologic Complete Response ◽

Neoadjuvant Treatment ◽

Oncologic Outcome ◽

Complete Response ◽

Rank Test ◽

Salvage Operation ◽

Clinical Complete Response ◽

Kaplan Meier

509 Background: Nonoperative management (NOM) of rectal cancer following a clinical complete response (cCR) to neoadjuvant therapy is a non-standard approach. We review our experience with NOM to evaluate safety and efficacy. Methods: A retrospective review of prospectively collected data between 2006 and 2014 was conducted. We compared patients completing neoadjuvant therapy for stage I to III rectal cancers who: a) achieved cCR and were treated with NOM, or b) underwent standard total mesorectal excision (TME) and achieved a pathologic complete response (pCR). Kaplan-Meier estimates and the log-rank test were used. Results: Seventy-three patients underwent NOM after cCR. From 369 rectal resections performed, 72 (20%) achieved pCR and form the comparison group. Median follow-up across both groups was 3.3 years. Rectal preservation was achieved in 56 (77%) of the patients treated with NOM. Of the 19 NOM patients with local regrowth, 18 were salvaged successfully with standard TME (n=16) or local excision (n=2), with one patient pending a salvage operation (n=1). No significant differences were noted in the number of distant recurrences between the NOM and pCR groups. Four-year disease-specific survival and overall survival between the two groups were not significantly different. Conclusions: In this highly selected group of patients with cCR to neoadjuvant treatment, NOM with surgical salvage of local tumor regrowth achieved local control in all patients. The oncologic outcome for NOM patients at 4 years was comparable to patients with pCR after rectal resection. These data continue to suggest that NOM does not compromise oncologic outcome, and that preservation of the rectum is achieved in a majority of patients. [Table: see text]

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Effect of neoadjuvant pertuzumab-containing regimens on pathologic complete response rates in stage II-III HER2-neu positive breast cancer: A retrospective, single institutional experience.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.580 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 580-580

Author(s):

Rashmi Krishna Murthy ◽

Takeo Fujii ◽

Kenneth R. Hess ◽

Akshara Singareeka Raghavendra ◽

Bora Lim ◽

...

Keyword(s):

Breast Cancer ◽

Targeted Therapy ◽

Clinical Stage ◽

Pathologic Complete Response ◽

Neoadjuvant Treatment ◽

Complete Response ◽

Stage Ii ◽

Her2 Positive ◽

Her2 Breast Cancer ◽

Positive Breast Cancer

580 Background: Pertuzumab (P) in combination with trastuzumab (H) based chemotherapy is currently FDA- approved as a standard neoadjuvant treatment for patients with clinical stage II-III HER2-positive (HER2+) breast cancer (BC). The chemotherapy backbone of HER2-targeted therapy varies and may include taxane (T) and/or anthracycline (A), or carboplatin (C). The goal of this study was to retrospectively evaluate the pathologic complete response (pCR) rate for HP-containing regimens compared to H containing regimens for stage II-III HER2+ BC. Methods: We identified all patients (n = 1150) with stage II-III HER2+ BC who received neoadjuvant HER2-targeted therapy from 2005 to 2016 through an institutional database. All patients underwent primary breast and lymph node surgery. pCR was defined as ypT0/is, ypN0. Univariate/multivariate logistic regression and chi-squared test for comparing proportions was used for the statistical analysis. Results: pCR was significantly higher for the HP group (n = 200) compared to the H group (n = 950): 44% vs. 41%, odds ratio = 1.8 (95% CI = 1.3, 2.5; P = 0.0002). Even with adjustment for all clinically significant factors (age, stage, tumor grade, hormone receptor (HR) status, A or C exposure), the improvement was statistically significant (adjusted OR = 2.1 (95% CI = 1.5, 2.9; P < 0.0001). The pCR rate by stage and HR status for the HP group is 62% vs. 55% (stage II vs. III) and 71% vs. 51% (HR- vs. HR+). The effect of P was not modified by HR status (HR-, OR = 2.3; HR+, OR = 1.7, P = 0.39) or by A (A-yes, OR = 1.8; A-no, OR = 2.6) (P = 0.28 for interaction) or C (C-yes, OR 2.6; C-no, OR = 1.8) (P = 0.30 for interaction). P was significantly more likely to be given to patients without A (36% vs. 10%, P < 0.0001) and more likely to be given to patients with C (30% vs. 14%, P < 0.001). In both groups, significant predictors of pCR were found to be stage, HR status, and C exposure. Conclusions: Pertuzumab containing regimens yield higher pCR rates compared to non-Pertuzumab containing regimens in stage II- III HER-2 positive breast cancer. The effect of Pertuzumab is not modified by anthracycline or carboplatin use.

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A phase II study of complete neoadjuvant therapy in rectal cancer (CONTRE): The Brown University Oncology Group.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.335 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 335-335 ◽

Cited By ~ 3

Author(s):

Kimberly Perez ◽

Victor Pricolo ◽

Matthew Vrees ◽

Thomas A. DiPetrillo ◽

Nicholas Oldenberg ◽

...

Keyword(s):

Rectal Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Pathologic Complete Response ◽

Neoadjuvant Treatment ◽

Complete Response ◽

Stage Ii ◽

R0 Resection ◽

Pelvic Mri ◽

Grade 3

335 Background: While preoperative chemoradiation followed by surgery is the standard approach for patients (pts) with newly diagnosed clinical stage II-III rectal cancer, many are unable to tolerate postoperative adjuvant chemotherapy which may compromise disease-free and overall survival. CONTRE is a multicenter phase II study designed to determine the feasibility of administering all chemotherapy prior to surgery and to assess its impact on pathologic complete response (pCR) and complete (R0) resection Methods: Pts with T3-4 and/or N1-2 rectal cancer, staged by endorectal ultrasound (ERUS) and pelvic MRI, receive modified (m) FOLFOX6 every 2 weeks x 8 cycles, followed by repeat MRI and proctoscopy to assess response. Pts then receive 50.4 Gy IMRT with 5-FU 225 mg/m2/day or capecitabine 825mg/m2 BID, 5 days per week during radiation, followed by surgery 4-8 weeks later. Results: Thus far, we have enrolled 36 of a planned 39 pts (median age 58, range 30-79; T2-1, T3-30, T4-2; N1-20, N2-7). 28 of the first 30 (93%) completed 8 cycles of mFOLFOX6. 26 pts have completed chemoradiation while 2 chose to proceed directly to surgery. All patients opted to receive capecitabine during radiation. Grade 3/4 toxicities during chemotherapy and chemoradiation have included diarrhea (16%) and neutropenia (12%), with grade 3 renal and cardiac toxicities reported in one patient each. A clinical complete response after chemotherapy alone was achieved in 3 of 29 (10%). Of the first 21 pts undergoing surgery, pCR has been achieved in 6 (29%) and R0 resections in 100%. Thus far, all pts have been able to undergo sphincter-sparing resections. Study accrual will be completed by the meeting. Conclusions: A larger proportion of stage II-III rectal cancer pts are able to complete mFOLFOX6 (>90% in our cohort) when administered prior to chemoradiation and surgery. Complete neoadjuvant treatment may represent a well-tolerated alternative to the current standard treatment sequence and a platform for the evaluation of novel therapeutics such as targeted agents during preoperative therapy. Funded in part by LIFEcycle, Inc. Clinical trial information: NCT01363843.

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Neoadjuvant therapy for rectal cancer: Mature results from NSABP protocol R-04.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.390 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 390-390 ◽

Cited By ~ 14

Author(s):

Carmen Joseph Allegra ◽

Greg Yothers ◽

Michael J O'Connell ◽

Mark S. Roh ◽

Robert W. Beart ◽

...

Keyword(s):

Rectal Cancer ◽

Primary Endpoint ◽

Clinical Stage ◽

Pathologic Complete Response ◽

Distant Metastases ◽

Complete Response ◽

Stage Ii ◽

Stage Iii ◽

Tumor Control ◽

R0 Resection

390 Background: The primary aims were to: 1) compare capecitabine (Cape) and continuous intravenous infusion (CVI) 5-FU combined with pelvic radiation therapy (RT) given preoperatively for patients (pts) with stage II or III rectal cancer; 2) determine whether the addition of oxaliplatin (Ox) would improve pt outcomes. Preliminary results focusing on pathologic complete response, sphincter-sparing surgery, surgical downstaging, and toxicity were presented at ASCO 2011 (Roh: J Clin Oncol 29: 2011 Ab 3503). Methods: Pts with clinical stage II or III rectal cancer undergoing preoperative RT (4,500cGy in 25 fractions over 5 wks + boost of 540cGy-1080cGy in 3-6 daily fractions) were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU (225mg/m2 5 days/wk), with or without intravenous Ox (50mg/m2 /wk x 5) or oral Cape (825 mg/m2 BID 5 days/wk), with or without Ox (50mg/m2/wk x 5). The primary endpoint of local-regional (L-R) tumor control included L-R tumor recurrence, less than an R0 resection (complete surgical resection), and no surgery. Results: From July 2004 to August 2010, 1608 patients were randomly assigned and 99.2% were eligible. There were no significant differences in L-R tumor control, DFS, or OS between regimens for either the 5-FU-Cape (L-R p=0.98) or the Ox-none (L-R p=0.70) comparisons. The addition of Ox was associated with significantly more grade 3-4 diarrhea (p<0.0001). Analysis of the primary endpoint showed 3-yr rates of L-R tumor control ranged from 87.4%-88.2%. 3-yr rates of L-R recurrence among pts who underwent R0 resection ranged from 2-4 % for stage II pts, and from 4-11% for stage III pts. 16% of stage II and 26% of stage III pts developed distant metastases by 5 yrs. From 84% to 97% of pts received >80% of the ideal chemotherapy dose in combination with preoperative RT. Conclusions: CVI 5-FU or oral Cape combined with RT produced similar outcomes and toxicity profiles. Because use of oral Cape avoids the need for central venous catheters and ambulatory infusion pumps, it can be considered a new standard of care in this setting. The addition of Ox provided no improvement in outcomes but did add significant toxicity. Clinical trial information: NCT00058474.

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CEA, EpCAM, αvβ6 and uPAR Expression in Rectal Cancer Patients with a Pathological Complete Response after Neoadjuvant Therapy

Diagnostics ◽

10.3390/diagnostics11030516 ◽

2021 ◽

Vol 11 (3) ◽

pp. 516

Author(s):

Daan Linders ◽

Marion Deken ◽

Maxime van der Valk ◽

Willemieke Tummers ◽

Shadhvi Bhairosingh ◽

...

Keyword(s):

Rectal Cancer ◽

Neoadjuvant Therapy ◽

Cancer Patients ◽

Pathological Complete Response ◽

Neoadjuvant Treatment ◽

Complete Response ◽

Response Evaluation ◽

Tumor Bed ◽

Upar Expression ◽

Diagnostic Biopsy

Rectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a pathological complete response (pCR) remains challenging. Targeted near-infrared fluorescence endoscopy is a potential tool to improve response evaluation. Promising tumor targets include carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), integrin αvβ6, and urokinase-type plasminogen activator receptor (uPAR). To investigate the applicability of these targets, we analyzed protein expression by immunohistochemistry and quantified these by a total immunostaining score (TIS) in tissue of rectal cancer patients with a pCR. CEA, EpCAM, αvβ6, and uPAR expression in the diagnostic biopsy was high (TIS > 6) in, respectively, 100%, 100%, 33%, and 46% of cases. CEA and EpCAM expressions were significantly higher in the diagnostic biopsy compared with the corresponding tumor bed (p < 0.01). CEA, EpCAM, αvβ6, and uPAR expressions were low (TIS < 6) in the tumor bed in, respectively, 93%, 95%, 85%, and 62.5% of cases. Immunohistochemical evaluation shows that CEA and EpCAM could be suitable targets for response evaluation after neoadjuvant treatment, since expression of these targets in the primary tumor bed is low compared with the diagnostic biopsy and adjacent pre-existent rectal mucosa in more than 90% of patients with a pCR.

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