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Reduced radiation dose for elective nodal irradiation in node-negative anal cancer: back to the roots?

Dosisreduzierte elektive Lymphknotenbestrahlung beim nodalnegativen Analkarzinom: Zurück zu den Wurzeln?



Chemoradiation (CRT) is the standard of care in patients with node-positive (cN+) and node-negative (cN0) anal cancer. Depending on the tumor size (T-stage), total doses of 50–60 Gray (Gy) in daily fractions of 1.8–2.0 Gy are usually applied to the tumor site. Inguinal and iliac lymph nodes usually receive a dose of ≥ 45 Gy. Since 2010, our policy has been to apply a reduced total dose of 39.6 Gy to uninvolved nodal regions. This paper provides preliminary results of the efficacy and safety of this protocol.

Patients and methods

Overall, 30 patients with histologically confirmed and node-negative anal cancer were treated in our department from 2009–2014 with definitive CRT. Histology all cases showed squamous cell carcinoma. A total dose of 39.6 Gy [single dose (SD) 1.8 Gy] was delivered to the iliac/inguinal lymph nodes. The area of the primary tumor received 50–59.4 Gy, depending on the T-stage. In parallel with the irradiation, 5-fluorouracil (5-FU) at a dose of 1000 mg/m2 was administered by continuous intravenous infusion over 24 h on days 1–4 and 29–32, and mitomycin C (MMC) at a dose of 10 mg/m2 (maximum absolute dose 14 mg) was administered on days 1 and 29. The distribution of the tumor stages was as follows: T1, n = 8; T2, n = 17; T3 n = 3. Overall survival (OS), local control (LC) of the lymph nodes, colostomy-free survival (CFS), and acute and chronic toxicities were assessed.


The median follow-up was 27.3 months (range 2.7–57.4 months). Three patients (10.0 %) died, 2 of cardiopulmonary diseases and one of liver failure, yielding a 3-year OS of 90.0 %. Two patients (6.7 %) relapsed early and received salvage colostomies, yielding a 3-year CFS of 93.3 %. No lymph node relapses were observed, giving a lymph node LC of 100 %. According to the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE V. 4.0), there were no grade IV gastrointestinal or genitourinary acute toxicities. Seven patients showed acute grade III perineal skin toxicity. Acute grade III groin skin toxicity was not observed.


Reducing the total irradiation dose to uninvolved nodal regions to 39.6 Gy in chemoradiation protocols for anal carcinoma was safe and effective, and a prospective evaluation in future clinical trials is warranted.



Die primäre Radio(chemo)therapie (RCT) ist die Therapie der Wahl beim nodalpositiven (cN+) und nodalnegativen (cN0) Analkarzinom. Abhängig von der Tumorgröße (T-Stadium) werden in der Primärtumorregion Gesamtdosen (GD) von 50–60 Gy mit täglichen Fraktionen zwischen 1,8–2,0 Gy eingestrahlt. Die elektive Bestrahlung des inguinalen/pelvinen Lymphabflusses (LAG) erfolgt in der Regel mit einer GD von ≥ 45 Gy. Seit 2010 erhielten Patienten mit einem cN0-Analkarzinom in unserer Klinik eine reduzierte GD im Bereich des inguinalen/iliakalen LAG mit 39,6 Gy [Einzeldosis (ED) 1,8 Gy]. Diese Publikation zeigt Sicherheit und Wirksamkeit dieses Protokolls.

Patienten und Methoden

Insgesamt wurden 30 Patienten mit einem nodalnegativen, histologisch gesicherten Analkarzinom untersucht, welche zwischen 2009 und 2014 eine primäre RCT in unserer Klinik erhielten. In allen Fällen handelte es sich histologisch um ein Plattenepithelkarzinom. Iliakal/inguinal wurde eine GD von 39,6 Gy (ED 1,8 Gy) eingestrahlt. Im Bereich der Primärtumorregion wurde T-Stadien-abhängig eine GD von 50–59,4 Gy eingestrahlt. Simultan zur Bestrahlung wurde 5- Fluorouracil (5-FU) als intravenöse Dauerinfusion mit einer Dosis von 1000 mg/m2 über 24 h an Tag 1–4 und Tag 29–32 sowie Mitomycin C (MMC) als Bolusgabe mit einer Dosis von 10 mg/m2 (Maximum 14 mg absolut) an Tag 1 und 29 gegeben. Die retrospektive Verteilung der Tumorstadien war wie folgt: 8-mal T1, 17-mal T2, 3-mal T3. Es wurden das Gesamtüberleben (OS), die lokale Kontrollrate (LC) der Lymphknoten, das kolostomiefreie Überleben (CFS) sowie Akut- und Spättoxizitäten analysiert.


Die mediane Nachbeobachtungszeit betrug 27,3 Monate (Spanne 2,7–57,4 Monate). Insgesamt 3 Patienten (10 %) verstarben nichttumorbedingt, (zwei kardiale Ereignisse, ein Leberversagen), so dass sich ein 3-Jahres-OS von 90,0 % ergab. Ein lokales Frührezidiv mit nachfolgender Kolostomie wurde bei 2 Patienten beobachtet (6,7 %). Ein Lymphknotenrezidiv trat im Beobachtungszeitraum nicht auf, so dass sich ein 3-Jahres-CFS von 93,3 % und eine LC der Lymphknoten von 100 % ergab. Akuttoxizitäten vom Grad 4 gemäß der Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE V. 4.0) wurden nicht beobachtet. Eine akute perineale Hautreaktion vom Grad 3 zeigten 7 Patienten. Akute Grad-3-Hautreaktionen im Leistenbereich traten nicht auf.


Eine reduzierte Strahlendosis von 39,6 Gy im Bereich klinisch nichtbefallener Lymphknoten war im Rahmen der durchgeführten Radiochemotherapie onkologisch sicher, gut verträglich und rechtfertig eine Evaluation in prospektiven Studien.

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Correspondence to Christoph Henkenberens.

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Conflict of interest

C. Henkenberens, D. Meinecke, M. Stoll, M. Bremer, and H. Christiansen state that there are no conflicts of interest.

The accompanying manuscript does not include studies on humans or animals.

Additional information

C. Henkenberens and D. Meinecke contributed equally to this work.

The data were presented at the 2014 DEGRO (German Society for Radiation Oncology) Annual Meeting in Düsseldorf, Germany.

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Henkenberens, C., Meinecke, D., Michael, S. et al. Reduced radiation dose for elective nodal irradiation in node-negative anal cancer: back to the roots?. Strahlenther Onkol 191, 845–854 (2015).

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