Marten S. Schilthuis

Prognostic Model for Survival in Patients With Early Stage Cervical Cancer

In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment.

Surgical Pathologic Factors That Predict Recurrence in Stage IB and IIA Cervical Carcinoma Patients with Negative Pelvic Lymph Nodes

The purpose of this analysis was to identify pathologic risk factors for recurrence and patterns of recurrence in patients with International Federation of Gynecology and Obstetrics Stage IB and IIA cervical carcinoma and negative pelvic lymph nodes after radical hysterectomy.

Squamous cell carcinoma of the vulva with bulky positive groin nodes—nodal debulking versus full groin dissection prior to radiation therapy

Patients with clinical palpable involved groin lymph nodes and squamous cell cancer of the vulva are frequently treated by a full inguinal-femoral lymph node dissection followed by adjuvant radiotherapy to the groins and pelvis. Theoretically, less radical surgery for the groin such as nodal debulking, where only the macroscopically involved nodes are resected, allowing radiotherapy to treat any remaining microscopic disease may potentially decrease morbidity without compromising survival The objective of this retrospective study was to compare the groin recurrence rate and survival (disease specific and overall survival) of patients with clinically involved groin nodes and squamous cell carcinoma of the vulva treated either by a full inguino-femoral lymphadenectomy or by a nodal debulking followed by radiotherapy. Forty patients from three separate databases who met these criteria were identified. Patients were treated either by a full inguino-femoral lymphadenectomy or by a debulking of the clinically involved inguinal lymph nodes. All patients received adjuvant radiotherapy to the groins. In these two groups, there was no difference in groin recurrence rate expressed as groin recurrence-free survival (P= 0.247). In a univariate analysis, both overall and disease-free survival were better in the group of patients treated by nodal debulking. However, in a multivariate analysis, other variables such as extracapsular growth were independent predictors for survival while the method of surgical dissection for the groin had no independent significant impact on survival.

Preoperative serum squamous cell carcinoma antigen levels in clinical decision making for patients with early-stage cervical cancer

PURPOSE To prevent morbidity associated with double modality treatment, early-stage cervical cancer patients should only be offered surgery when there is a low likelihood for adjuvant radiotherapy. We analyzed whether serum squamous cell carcinoma antigen (SCC-ag) analysis allows better preoperative identification of patients with a low likelihood for adjuvant radiotherapy than currently used clinical parameters. PATIENTS AND METHODS In a cohort study, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, and preoperative serum SCC-ag levels, as determined by enzyme immunoassay, were related to the frequency of postoperative indications for adjuvant radiotherapy in 337 surgically treated, FIGO stage IB/IIA, squamous cell cervical cancer patients. RESULTS In patients with normal preoperative SCC-ag, 16% of IB1 and 29% of IB2/IIA had postoperative indications for adjuvant radiotherapy, in contrast to 57% of IB1 and 74% of IB2/IIA patients with elevated (> 1.9 ng/mL) serum SCC-ag (P < .001). Serum SCC-ag was the only independent predictor for a postoperative indication for radiotherapy (odds ratio, 7.1; P < .001). Furthermore, in IB1 patients that did not have indications for adjuvant radiotherapy, 15% of patients with elevated preoperative serum SCC-ag levels recurred within 2 years, compared with 1.6% of patients with normal serum SCC-ag levels (P = .02). CONCLUSION In early-stage cervical cancer, determination of serum SCC-ag levels allows more refined preoperative estimation of the likelihood for adjuvant radiotherapy than current clinical parameters, and simultaneously identifies patients at high risk for recurrence when treated with surgery only. The role of preoperative serum SCC-ag in the management of patients with early-stage cervical cancer deserves further investigation.

Prognostic value of bilateral positive nodes in squamous cell cancer of the vulva.

Objectives: The aim of the current study was, first, to determine whether laterality of lymph node metastases has prognostic significance, independent of the number of lymph node metastases. Second was to determine the prognostic significance of extracapsular spread irrespective of the number of lymph node metastases. Methods: Data on 134 patients with stage III/IVA vulva cancer from 1982 till 2004 and treated with curative intent in either the Academic Medical Centre in Amsterdam or the Mercy Hospital for Women in Melbourne were reviewed. The impact of the number of lymph node metastases, extracapsular spread, and bilateral existence of lymph node metastases on survival was determined. Results: The bilateral presence of lymph node metastases is not a significant predictor for survival if a correction is made for the number of lymph node metastases (hazards ratio, 1.31; 95% confidence interval, 0.68-2.51; P = 0.420). If extracapsular spread is put into the model as well, this is the only parameter of prognostic significance in multivariate analysis (hazards ratio, 5.27; 95% confidence interval, 2.60-10.67; P < 0.001). The five-year survival of patients with extracapsular spread is only 31%, which is considerably lower than the 80% survival of patients with only intracapsular metastases. Conclusions: In conclusion, there is growing evidence that bilateral existence of lymph node metastases is not a sufficient variable to qualify stage. Extracapsular spread, however, seems to be the most valuable lymph node-associated prognostic factor for survival.

Intestinal obstruction in patients with advanced ovarian cancer.

A retrospective analysis of the management of intestinal obstruction in 31 patients with advanced ovarian carcinoma is described. Between 1981 and 1992 31 patients developed intestinal obstruction after their initial treatment. Nineteen patients underwent surgery, while the remaining 12 were treated conservatively. Careful evaluation with contrast studies of both the small intestine and colon is recommended to improve the prediction of site(s) of obstruction, and may reduce the number of unsuccessful operative procedures. Fifteen of the surgically treated patients survived for a period of 60 days or more. The majority, 13, were discharged to their homes after an average hospital stay of 24 days. Major postoperative complications occurred in three of the 19 patients. There was no surgical-related mortality. Two patients died within 30 days postoperatively (urosepsis and advanced tumor). While the median survival in the 19 surgical treated patients was 109 days (range 15–775), the conservatively treated 12 patients survived for a mean of 37 days (range 6–260). Surgical management of intestinal obstruction in selected cases is feasible and improves quality of life substantially.

Can We Predict Vesicovaginal or Rectovaginal Fistula Formation in Patients With Stage IVA Cervical Cancer

Introduction: Patients with cervical carcinoma that invade the bladder or rectum (International Federation of Obstetrics and Gynecology stage IVA) have a high risk to develop vesicovaginal and/or rectovaginal fistulae. If we could identify pretreatment factors that predict fistula formation, these patients could be offered less debilitating treatment. Materials and Methods: Data were retrieved from the database of consecutive patients diagnosed with stage IVA cervical cancer from 1992 to 2008. Overall survival and fistula-free survival were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to study the association between pretreatment prognostic variables and fistula formation. Results: Thirty patients with stage IVA cervical cancer were diagnosed. Extension to the bladder was present in 27 patients; three patients had only rectal involvement. Twenty-three patients (77%) had curative radiotherapy with or without chemotherapy and/or hyperthermia. Seven patients (23%) received only palliative therapy or no treatment at all. The 5-year overall survival in the curatively treated group was 42%. Five (22%) of these 23 patients developed one or more fistulae: 3 vesicovaginal, 1 rectovaginal, and 1 vesicovaginal and rectovaginal fistulae. The 5-year fistula-free survival of this group was 64%. No significant association was found between the prognostic variables and fistula formation. Conclusions: The risk to develop vesicovaginal and/or rectovaginal fistulae is high after curative radiotherapy with or without chemotherapy and/or hyperthermia in patients with stage IVA cervical cancer. We could not identify further pretreatment factors that might have predicted fistula formation.

Feasibility, toxicity, and preliminary results of weekly loco-regional hyperthermia and cisplatin in patients with previously irradiated recurrent cervical carcinoma or locally advanced bladder cancer

PURPOSE The biological rationale for combining locoregional hyperthermia (HT) with cisplatin (CDDP) is the potentiating effect of HT on CDDP uptake and cytotoxicity. Feasibility, toxicity, and preliminary results of a clinical trial of weekly loco-regional HT in combination with cisplatin are described in this article. METHODS AND MATERIALS Patients with previously irradiated unresectable local recurrent cervical carcinoma or locally advanced bladder carcinoma were treated with weekly cycles of locoregional HT (70 MHz four antenna phased array system) for 1 h and CDDP 50 mg/m(2) IV for a maximum of 12 courses. RESULTS Fourteen patients, 10 patients with recurrent cervical carcinoma and 4 with locally advanced bladder carcinoma, were entered in this study. A total of 100 cycles were given. Overall toxicity was acceptable; Grade 3 (WHO) toxicity (gastrointestinal, hematological, and neurotoxicity) was observed in 5 out of 14 patients. No Grade 4 toxicity was seen. Subcutaneously fatty necrosis due to HT occurred in 11% of the cycles, while two patients developed skin burns. Two out of 10 patients with recurrent cervical carcinoma were not evaluable for response. Four out of eight evaluable cervical carcinoma patients responded (two pathologic complete responses, one pathologic confirmed partial response, one partial response): response rate 50% (95% confidence interval 15.7-84.3%). Salvage surgery became possible in three out of four responding patients, whose tumors were previously considered unresectable. Two out of the four evaluable patients with locally advanced bladder carcinoma responded (two partial responses). CONCLUSIONS Weekly loco-regional HT and CDDP 50 mg/m(2)/week for a maximum of 12 courses is feasible with an acceptable toxicity, which seems not to be enhanced by the addition of loco-regional HT. The encouraging preliminary results of this treatment schedule warrant further study, especially in patients with previously irradiated recurrent cervical carcinomas.

On verification of hyperthermia treatment planning for cervical carcinoma patients.

Purpose: The aim of this study was to verify hyperthermia treatment planning calculations by means of measurements performed during hyperthermia treatments. The calculated specific absorption rate (SARcalc) was compared with clinically measured SAR values, during 11 treatments in seven cervical carcinoma patients. Methods: Hyperthermia treatments were performed using the 70 MHz AMC-4 waveguide system. Temperatures were measured using multisensor thermocouple probes. One invasive thermometry catheter in the cervical tumour and two non-invasive catheters in the vagina were used. For optimal tissue contact and fixation of the catheters, a gynaecological tampon was inserted, moisturized with distilled water (4 treatments), or saline (6 treatments) for better thermal contact. During one treatment no tampon was used. At the start of treatment the temperature rise (ΔTmeas) after a short power pulse was measured, which is proportional to SARmeas. The SARcalc along the catheter tracks was extracted from the calculated SAR distribution and compared with the ΔTmeas-profiles. Results: The correlation between ΔTmeas and SARcalc was on average R = 0.56 ± 0.28, but appeared highly dependent on the wetness of the tampon (preferably with saline) and the tissue contact of the catheters. Correlations were strong (R ∼ 0.85–0.93) when thermal contact was good, but much weaker (R ∼ 0.14–0.48) for cases with poor thermal contact. Conclusion: Good correlations between measurements and calculations were found when tissue contact of the catheters was good. The main difficulties for accurate verification were of clinical nature, arising from improper use of the gynaecological tampon. Poor thermal contact between thermocouples and tissue caused measurement artefacts that were difficult to correlate with calculations.

Validation of existing prognostic models in patients with early-stage cervical cancer

OBJECTIVE Models that predict survival and recurrence in patients with early-stage cervical cancer are important tools in patient management. We validated 12 existing prognostic models in an independent population of patients with early-stage cervical cancer. MATERIALS AND METHODS We searched the literature for prognostic models in patients with surgically treated early-stage cervical cancer. The prognostic performance of these models was assessed in a consecutive group of surgically treated patients with early-stage cervical cancer treated in our hospital between 1982 and 2004. The performance of the models was visually assessed with calibration plots, which display the relation between the predicted and observed survival. RESULTS Twelve published prognostic models met the inclusion criteria. The models categorized the patients into two to four risk groups. Prognostic factors most frequently used in these models were depth of invasion, lymph node metastasis, vascu/vascular space involvement, and tumor size. The models were validated in 563 consecutive patients with early-stage cervical cancer. All of the models underestimated the recurrence-free survival or disease-specific survival in our patients. Only two models performed reasonably well in our population. The use of more than three prognostic categories in the models was not meaningful. CONCLUSION In general, the models underestimated the survival. Only 2 of the 12 prognostic models for patients with early-stage cervical cancer were valid for the prediction of the recurrence-free or disease-specific survival in our patient population.