Abstract
Background and purpose
It has been previously reported that a short FOLFOX-4 induction significantly improves pathologic complete response in locally advanced rectal cancer (LARC) patients treated with preoperative chemoradiation (CRT). In a larger and updated patient series, we analyzed FOLFOX-4 efficacy in terms of sphincter preservation and long-term outcomes.
Patients and methods
From January 1995 to December 2010, 335 LARC patients were treated with preoperative chemoradiation (4500–5040 cGy). Starting in May 2001, 207 consecutive patients additionally received induction FOLFOX-4. Surgery was performed 6 weeks (range 3–12 weeks) after chemoradiation.
Results
Incidence of total tumor (63 vs. 54 %, p = 0.02) and nodal downstaging (60 vs. 43 %, p = 0.002) was significantly increased by induction FOLFOX-4. In an analysis of tumors located below 5 cm from the anal verge (n = 114, 34 %), sphincter preservation was feasible in 30 % in the FOLFOX-4 versus 13 % in the upfront CRT group (p = 0.04). Median follow-up time for the entire cohort of patients was 72.6 months (range 4–205 months). FOLFOX-4 was not associated with superior locoregional control (HR 0.88, p = 0.78), disease-free survival (HR 0.83, p = 0.55), distant metastases-free survival (HR 0.94, p = 0.81), or cancer-specific survival (HR 0.70, p = 0.15).
Conclusion
Short-intense induction FOLFOX-4 significantly improves downstaging and sphincter preservation in low rectal tumors. Long-term outcomes were not improved in the FOLFOX-4 group of patients.
Zusammenfassung
Hintergrund und Ziel
Es wurde bereits berichtet, dass eine kurze FOLFOX-4-Induktion das gesamte pathologische Ansprechen bei Patienten mit lokal fortgeschrittenem Rektumkarzinom (LARC), die präoperativ mittels Strahlenchemotherapie (CRT) behandelt wurden, signifikant verbessert. In einer größeren und aktualisierten Patientengruppe analysierten wir die FOLFOX-4-Wirksamkeit hinsichtlich Sphinktererhalt und Langzeitergebnissen.
Patienten und Methoden
Von Januar 1995 bis Dezember 2010 wurden 335 LARC-Patienten präoperativ mit einer Strahlenchemotherapie (4500–5040 cGy) behandelt. Seit Mai 2001 erhielten 207 aufeinanderfolgende Patienten zusätzlich eine FOLFOX-4-Induktion. Die Operation wurde 6 Wochen (Spanne 3–12 Wochen) nach der Strahlenchemotherapie durchgeführt.
Ergebnisse
Durch die FOLFOX-4-Induktion nahm die Inzidenz des Gesamttumors (63 vs. 54 %; p = 0,02) und das Lymphknoten-Downstaging (60 vs. 43 %; p = 0,002) deutlich zu. In einer Analyse von Tumoren, die weniger als 5 cm vom analen Rand entfernt waren (n = 114 waren 34 %), waren bei 30 % in der FOLFOX-4- und bei 13 % in der vorausgegangenen CRT-Gruppe (p = 0,04) ein Sphinktererhalt möglich. Das mediane Follow-up für die gesamte Patientenkohorte betrug 72,6 Monate (Spanne 4–205 Monate). FOLFOX-4 war nicht mit einer höheren lokoregionalen Kontrolle (HR 0,88; p = 0,78), besserem krankheitsfreiem (HR 0,83; p = 0,55), fernmetastasenfreiem (HR 0,94; p = 0,81) oder krebsspezifischem Überleben (HR 0,70; p = 0,15) assoziiert.
Schlussfolgerung
Die kurze intensive Induktion von FOLFOX-4 verbessert signifikant das Downstaging und den Sphinktererhalt bei Tumoren im unteren Rektumdrittel. Die Langzeitergebnisse besserten sich in der FOLFOX-4-Gruppe nicht.
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Acknowledgment
Supported in part by a grant from the Health Institute of Research Carlos III, Spanish Ministry of Science and Innovation (project code PI11-02908).
Compliance with ethical guidelines
Conflict of interest. F.A. Calvo C.V. Sole, J. Serrano, E. del Valle, M. Rodriguez, A. Muñoz-Calero, J.L. García-Sabrido, P. Garcia-Alfonso, I. Peligros, and E. Alvarez state that there are no conflicts of interest.
All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.
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Calvo, F., Sole, C., Serrano, J. et al. Preoperative chemoradiation with or without induction oxaliplatin plus 5-fluorouracil in locally advanced rectal cancer. Strahlenther Onkol 190, 149–157 (2014). https://doi.org/10.1007/s00066-013-0469-0
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DOI: https://doi.org/10.1007/s00066-013-0469-0
Keywords
- Neoadjuvant oxaliplatin
- Locally advanced rectal cancer
- Long-term outcomes
- External beam radiation therapy
- FOLFOX-4