Gynecologic examination and cervical biopsies after (chemo) radiation for cervical cancer to identify patients eligible for salvage surgery

Nijhuis, Esther R.; Zee, Ate G.J. van der; Hout, B.A. in ’t; Boomgaard, J; Hullu, Joanne A. de; Pras, Elisabeth; Hollema, Harry; Aalders, Jan G.; Nijman, Hans W.; Willemse, Pax H.B.; Mourits, Marian J.E.

doi:10.1016/j.ijrobp.2006.05.039

Cited by 25 publications

(32 citation statements)

References 13 publications

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“…The cervical cancer patients with tumors expressing TRAIL (75.7%) experienced less often a pathological complete response than those expressing no TRAIL (66.3% versus 78.9% OR in a multivariate analysis 2.09, p value #0.05). TRAIL expression, however, did not correlate with DSS, which in part may be caused by the fact that a proportion of patients with residual tumor after radiotherapy were salvaged by surgery, which in our institution is the standard of care for patients with resectable residual disease (23).…”

Section: Discussioncontrasting

confidence: 55%

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The Prognostic Value of TRAIL and its Death Receptors in Cervical Cancer

Maduro

Noordhuis

Hoor

et al. 2009

International Journal of Radiation Oncology*Biology*Physics

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Section: Discussioncontrasting

confidence: 55%

“…As mentioned earlier, patients with residual disease after (chemo-)radiation may be salvaged by surgery. Nijhuis et al previously showed in a similar population that 38% of the patients not having complete response after radiotherapy still achieve long-term complete remission after salvage surgery (23).…”

Section: Discussionmentioning

confidence: 92%

The Prognostic Value of TRAIL and its Death Receptors in Cervical Cancer

Maduro

Noordhuis

Hoor

et al. 2009

International Journal of Radiation Oncology*Biology*Physics

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“…In the period up to 1993, eligible patients underwent an additive hysterectomy 6 to 8 wk after completion of (chemo)radiation. After 1993, only patients with residual disease in a biopsy taken 8 to 10 wk after completion of primary treatment underwent surgery (21). Hysterectomy or biopsy after (chemo)radiation was only done when a patient (technically) was judged to be operable.…”

Section: Methodsmentioning

confidence: 99%

Expression of Epidermal Growth Factor Receptor (EGFR) and Activated EGFR Predict Poor Response to (Chemo)radiation and Survival in Cervical Cancer

Noordhuis

Eijsink

Hoor

et al. 2009

Clinical Cancer Research

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100

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Purpose: Activation of the epidermal growth factor receptor (EGFR) signaling pathway has been reported to induce resistance to (chemo)radiation in cancers, such as head and neck cancer, whereas EGFR-targeted agents in combination with (chemo)radiation seem to improve treatment efficacy. The aim of this study was to determine the relation between proteins involved in the EGFR pathway and response to (chemo)radiation and survival in a large, well-documented series of cervical cancer patients. Experimental Design: Pretreatment tissue samples of 375 consecutive International Federation of Gynecologists and Obstetricians stage Ib to IVa cervical cancer patients treated with (chemo)radiation between January 1980 and December 2006 were collected. Clinicopathologic and follow-up data were prospectively obtained during standard treatment and follow-up. Protein expression of EGFR, phosphorylated EGFR (pEGFR), PTEN, phosphorylated AKT, and phosphorylated extracellular signal-regulated kinase (pERK) was assessed by immunohistochemistry on tissue microarrays. Results: EGFR staining was present in 35.3%, pEGFR in 19.7%, PTEN in 34.1%, phosphorylated AKT in 4.1%, and pERK in 29.2% of tumors. pEGFR staining was related to PTEN (P = 0.001) and pERK staining (P = 0.004). EGFR staining was inversely related to PTEN (P = 0.011). In multivariate analysis, membranous staining of EGFR [hazard ratio (HR), 1.84; 95% confidence interval (95% CI), 1.20-2.82; P = 0.005] and cytoplasmic staining of pEGFR (HR, 1.71; 95% CI, 1.11-2.66; P = 0.016) were independent predictors of poor response to (chemo)radiation. Membranous EGFR staining also was an independent prognostic factor for poor disease-specific survival (HR, 1.54; 95% CI, 1.09-2.17; P = 0.014). Conclusions: EGFR and pEGFR immunostainings are frequently observed and independently associated with poor response to therapy and disease-specific survival in cervical cancer patients primarily treated by (chemo)radiation. Our data present the EGFR pathway as a promising therapeutic target in already ongoing clinical trials. (Clin Cancer Res 2009;15(23):7389-97) Standard treatment of locally advanced cervical cancer has changed from radiotherapy alone to concurrent platinum-based chemoradiation. Despite this change, the 5-year survival in patients with locally advanced cervical cancer is still ∼52% (1). Currently, there are no (biological) markers available that accurately predict response to (chemo)radiation.Epidermal growth factor receptor (EGFR) is involved in the ErbB signaling pathway, which is often dysregulated in cancer. Autophosphorylation of EGFR to phosphorylated EGFR (pEGFR) leads to activation of two downstream pathways: the Ras/Raf/ mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase/ERK pathway and the phosphatidylinositol 3-kinase/ AKT pathway. PTEN (phosphatase and tensin homologue deleted on

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“…In the few papers addressing this issue, verification was done by biopsies. 40 Routine D&C has never been performed before, but is theoretically the better way. Although biopsy potentially can be done at a wrong position due to vaginal adhesions, D&C under sonographic guidance definitely meets the place of cancer origin.…”

Section: Discussionmentioning

confidence: 99%

“…However, there was also often a bias in the indication for surgery in these facilities. Nijhuis et al 40 Real benefit of salvage surgery after primary radiation/ RCTX is also controversially discussed. Kunos et al 20 found a 10-year OS in patients initially staged bulky IB with good response of 76% compared to 52% in poor responders.…”

Section: Discussionmentioning

confidence: 99%