Search

Previously, we suggested that patients with cervical cancer (CC) with tumors ≤2 cm on preoperative magnetic resonance imaging (MRI) are safe candidates for laparoscopic radical hysterectomy (LRH). Here, we aim to investigate whether LRH deteriorates the prognosis of patients with incidentally identified high-risk factors; lymph node metastasis (LNM) or parametrial invasion (PMI). We identified patients with 2009 FIGO stage IB1 CC who underwent Type C LRH or open radical hysterectomy (ORH) at three tertiary hospitals between 2000 and 2019. Those with a tumor ≤2 cm on preoperative MRI who were not suspicious of LNM or PMI preoperatively were included, while those who were indicated to receive adjuvant treatment but did not actually receive it were excluded. Survival outcomes were compared between the LRH and ORH groups in the overall population, then narrowed down to those with LNM, and then to those with PMI. In total, 498 patients were included: 299 in the LRH group and 199 in the ORH group. The LRH and ORH groups showed similar 3-year progression-free survival (PFS) (94.0% vs. 93.6%; P = 0.615) and 5-year overall survival (OS) rates (97.2% vs. 96.8%; P = 0.439). On pathologic examination, 49 (9.8%) and 16 (3.2%) patients had LNM and PMI, respectively, and 10 (2.0%) had both. In the LNM subgroup, 5-year PFS rate was not significantly different between the LRH and ORH groups (73.2% vs. 91.7%; P = 0.169). In the PMI subgroup, no difference in PFS was observed between the two groups (P = 0.893). LRH might not deteriorate recurrence and mortality rates in CC patients with tumors ≤2 cm when adjuvant treatment is appropriately administered, even if pathologic LNM and PMI are incidentally identified. • We investigated whether LRH deteriorates the prognosis of patients with incidentally identified high-risk factors. • In the LNM subgroup, the ORH group had a better PFS than the LRH group without statistical significance. • In the PMI subgroup, no difference in PFS was observed between the two groups. [ABSTRACT FROM AUTHOR]

To investigate the impact of conization on survival outcomes and to identify a specific population that might benefit from conization before radical hysterectomy (RH) in patients with early-stage cervical cancer. From six institutions in Korea, we identified node-negative, margin-negative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who underwent primary type C RH between 2006 and 2021. The patients were divided into multiple groups based on tumor size, surgical approach, and histology. We performed a series of independent 1:1 propensity score matching and compared the survival outcomes between the conization and non-conization groups. In total, 1254 patients were included: conization (n = 355) and non-conization (n = 899). Among the matched patients with a tumor size of >2 cm, the conization group showed a significantly better 3-year disease-free survival (DFS) rate compared with the non-conization group when RH was conducted via minimally invasive surgery (MIS), in those with squamous cell carcinoma (96.3% vs. 87.4%, P = 0.007) and non-squamous cell carcinoma (97.0% vs. 74.8%, P = 0.021). However, no difference in DFS was observed between the two groups among the matched patients with a tumor size of ≤2 cm, regardless of surgical approach or histological type. In patients who underwent MIS RH, DFS significantly worsened as the residual tumor size increased (P < 0.001). Cervical conization was associated with a lower recurrence rate in patients with early-stage cervical cancer with a tumor size of >2 cm who underwent primary MIS RH. Cervical conization may be performed prior to MIS RH to minimize the uterine residual tumor. • We investigated survival impact of conization before RH on early cervical cancer. • A series of independent sample matching were performed in various patient groups. • Conization lowered relapse of MIS RH in patients with tumors >2 cm but not ≤2 cm. • Conization may be performed before MIS RH to minimize the uterine residual tumor. [ABSTRACT FROM AUTHOR]

To compare survival outcomes of minimally invasive surgery (MIS) and open surgery for radical hysterectomy (RH) in early cervical cancer patients with histologic subtypes of usual-type adenocarcinoma and adenosquamous carcinoma. From two centers' cervical cancer cohorts, patients with 2009 FIGO stage IB1–IB2 who underwent RH between 2007 and 2020 were retrospectively identified. Patients with usual-type adenocarcinoma and adenosquamous carcinoma were included in the analysis after pathologic review according to the updated World Health Organization Classification of Tumors. Clinicopathologic characteristics and survival outcomes were compared in terms of open surgery or MIS. This study included 161 patients. No significant differences were noted in overall survival (OS; P = 0.241) and disease-free survival (DFS; P = 0.156) between patients with usual-type adenocarcinoma (n = 136) and those with adenosquamous carcinoma (n = 25). MIS RH group (n = 99) had a significantly smaller tumor size (P < 0.001), lesser pathologic parametrial invasion (P = 0.001), and lesser lymph node metastasis (P < 0.001) than open RH group (n = 62). MIS and open RH groups showed similar OS (P = 0.201) and 3-year DFS rate (87.9% vs. 75.1%; P = 0.184). In multivariate analysis, worse DFS was not associated with MIS (P = 0.589) but was associated with pathologic parametrial invasion (adjusted HR, 3.41; 95% CI, 1.25–9.29; P = 0.016). Consistent results were observed among patients with usual-type adenocarcinoma; MIS was not associated with worse DFS. Comparable survival outcomes were found for MIS and open RH in early-stage cervical usual-type adenocarcinoma and adenosquamous carcinoma. Although MIS RH was not a poor prognostic factor, pathologic parametrial invasion was significantly associated with worse DFS in cervical usual-type adenocarcinoma and adenosquamous carcinoma. • We examined survival after RH in early cervical cancer with usual-type adenocarcinoma and adenosquamous carcinoma. • We re-classified the cases pathologically according to the updated WHO Classification of Tumors. • Overall, minimally invasive RH was not associated with disease recurrence and mortality rates. • Consistent results were observed among patients with usual-type adenocarcinoma. [ABSTRACT FROM AUTHOR]

To ascertain whether cervical conization before radical hysterectomy (RH) has a protective effect on survival outcomes in early cervical cancer, taking into account the surgical approach. From cervical cancer cohorts of two institutions, we identified node-negative, margin-negative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who received primary Type C RH between July 2006 and June 2020. Patients were divided into conization group (n = 144) and control group (n = 434). We conducted three independent 1:1 propensity score matching processes for histology, lymphovascular space invasion, cervical tumor size, and surgical approach (all patients, those who underwent open surgery, and those who underwent minimally invasive surgery [MIS]). Survival outcomes were compared. Overall, the conization group had less cervical tumor size and received MIS more frequently (P = 0.010) and adjuvant treatment less often (P = 0.002) versus the controls. After matching, the conization group showed significantly better disease-free survival (DFS) versus control (3-year DFS rate, 94.2% vs. 86.3%; P = 0.012), but similar overall survival. Among the open RH matched patients (n = 96), no difference in DFS was observed between the conization and control groups (P = 0.984). In contrast, among the MIS RH matched patients (n = 192), the conization group showed significantly better DFS versus control (3-year DFS rate, 95.7% vs. 82.9%; P = 0.005). In multivariate analysis adjusting for cervical tumor size and adjuvant treatment, conization was identified as an independent favorable prognostic factor for DFS (adjusted HR, 0.318; 95% CI, 0.134–0.754; P = 0.009). Preoperative cervical conization might reduce the disease recurrence rate in early cervical cancer patients who undergo primary MIS RH. • We investigated survival impact of preoperative conization on IB1 cervical cancer. • Post-matching, the conization group had significantly better disease-free survival. • Conization lowered recurrence of minimally invasive radical hysterectomy patients. • Conization may improve minimally invasive radical hysterectomy results. [ABSTRACT FROM AUTHOR]

Background: To determine whether additional chemotherapy after concurrent chemoradiation (CCRT) improves survival outcomes in patients with early cervical cancer who undergo radical hysterectomy (RH).Methods: We included high- or intermediate-risk patients from two institutions, with 2009 FIGO stage IB-IIA, who underwent primary RH and pelvic lymphadenectomy between January 2007 and June 2020, and had completed adjuvant CCRT. Survival outcomes were compared between patients who received additional chemotherapy (study group) and those who did not (control group).Results: A total of 198 patients were included in this analysis. The study (n = 61) and control groups (n = 137) had similar patient age, histologic cancer type, 2009 FIGO stage, and tumor size. However, minimally invasive surgery was performed less frequently in the study group than in the control group (19.7% vs. 46.0%, P < 0.001). The presence of pathologic risk factors was similar, except for lymph node metastasis, which was more frequent in the study group (72.1% vs. 46.0%; P = 0.001). In survival analyses, no differences in the disease-free survival (DFS; P = 0.539) and overall survival (OS; P = 0.121) were observed between the groups. Multivariate analyses adjusting for surgical approach and other factors revealed that additional chemotherapy was not associated with DFS (adjusted HR, 1.149; 95% CI, 0.552-2.391; P = 0.710) and OS (adjusted HR, 1.877; 95% CI, 0.621-5.673; P = 0.264). The recurrence patterns did not differ with additional chemotherapy. Consistent results were observed in a subset of high-risk patients (n = 139).Conclusions: Additional chemotherapy after CCRT might not improve survival outcomes in patients with early cervical cancer who undergo RH. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the impact of sarcopenia and body composition change during primary treatment on survival outcomes in patients with early cervical cancer. We retrospectively identified patients diagnosed with 2009 International Federation of Gynecology and Obstetrics stage IB1-IIA2 cervical cancer who underwent primary radical hysterectomy between 2007 and 2019. From pre-treatment CT scans (n = 306), the skeletal muscle area at the third lumbar vertebra (L3) and the waist skeletal muscle volume were measured using an artificial intelligence-based tool. These values were converted to the L3 and volumetric skeletal muscle indices by normalization. We defined L3 and volumetric sarcopenia using 39.0 cm2/m2 and the first quartile (Q1) value, respectively. From pre- and post-treatment CT scan images (n = 192), changes (%) in waist skeletal muscle and fat volumes were assessed. With the use of Cox regression models, factors associated with progression-free survival (PFS) and overall survival (OS) were analyzed. Between the L3 sarcopenia and non-sarcopenia groups, no differences in PFS and OS were observed. In contrast, volumetric sarcopenia was identified as a poor prognostic factor for PFS (adjusted hazard ratio [aHR], 1.874; 95% confidence interval [CI], 1.028–3.416; p = 0.040) and OS (aHR, 3.001; 95% CI, 1.016–8.869; p = 0.047). During primary treatment, significant decreases in waist skeletal muscle (median, −3.9%; p < 0.001) and total fat (median, −5.3%; p < 0.001) were observed. Of the two components, multivariate analysis revealed that the waist fat gain was associated with worse PFS (aHR, 2.007; 95% CI, 1.009–3.993; p = 0.047). The coexistence of baseline volumetric sarcopenia and waist fat gain further deteriorated PFS (aHR, 2.853; 95% CI, 1.257–6.474; p = 0.012). In conclusion, baseline volumetric sarcopenia might be associated with poor survival outcomes in patients with early cervical cancer undergoing primary RH. Furthermore, sarcopenia patients who gained waist fat during primary treatment were at a high risk of disease recurrence. [ABSTRACT FROM AUTHOR]

To compare survival outcomes of primary laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) in patients with FIGO stage IB cervical cancer. We retrospectively identified stage IB1–IB2 cervical cancer patients who received either LRH (n = 343) or ORH (n = 222) at two tertiary institutional hospitals between 2000 and 2018. To adjust for confounders, we conducted Mahalanobis distance-based sample matching for stage, histology, cervical mass size, parametrial invasion, and lymph node metastasis. Then, survival outcomes were compared between the matched groups. Through the independent matching processes, we narrowed the study population to stage IB1 patients and stage IB1 patients with tumor size ≤2 cm on pre-operative MRI. After matching, LRH group showed poorer progression-free survival (PFS) than ORH group (3-year: 85.4% vs. 91.8%; P = 0.036), whereas no significant difference in overall survival (OS) was found. Regarding recurrence patterns, no significant differences in the incidences of pelvic, retroperitoneal lymph node and abdominal recurrences, or distant metastasis were observed between the two groups. Among the matched patients with stage IB1 who had cervical mass size ≤2 cm, the LRH and ORH groups showed similar PFS (3-year: 90.0% vs. 93.1%; P = 0.8) and OS (5-year: 98.6% vs. 96.4%; P = 0.6). Despite the retrospective design, our matched cohort study suggests that ORH might be preferable for the surgical treatment of FIGO stage IB cervical cancer. However, in stage IB1 patients with tumor size ≤2 cm, LRH might be applicable, as equivalent outcomes were found regardless of the surgical approach. Further prospective studies are warranted. • We conducted a matching study to investigate survival of laparoscopic radical hysterectomy (LRH) in stage IB cervical cancer. • After matching, LRH group showed a higher recurrence rate compared to open group, whereas overall survival was not different. • In stage IB1 patients with tumor size ≤2 cm, equivalent survival outcomes were observed regardless of the surgical approach. [ABSTRACT FROM AUTHOR]

Abstract Objective To compare survival outcomes of minimally invasive surgery (MIS) and conventional open surgery for radical hysterectomy (RH) among patients with early-stage cervical cancer (CC). Methods We retrospectively identified stage IB1-IIA2 CC patients who underwent either laparoscopic or open Type C RH between 2000 and 2018. Patients' clinicopathologic characteristics and survival outcomes were compared according to the surgical approach. For a more robust statistical analysis, we narrowed the study population down to the patients with stage IB1 who underwent pre-operative MRI. Results In total, 435 and 158 patients were assigned to open surgery and MIS groups, respectively. MIS group had significantly less parametrial invasion (6.3% vs. 15.4%; P = 0.004). Despite similar proportions of patients received adjuvant treatment, concurrent chemoradiation therapy was performed less frequently in MIS group. After a median follow up of 114.8 months, the groups showed similar overall survival; however, MIS group displayed poorer progression-free survival (PFS; 5-year rate, 78.5% vs. 89.7%; P < 0.001). Multivariate analyses identified MIS as an independent poor prognostic factor for PFS (adjusted HR, 2.883; 95% CI, 1.711–4.859; P < 0.001). Consistent results were observed among 349 patients with stage IB1: MIS was associated with higher recurrence rates (adjusted HR, 2.276; 95% CI, 1.039–4.986; P = 0.040). However, MIS did not influence PFS of stage IB1 patients with cervical mass size ≤2 cm on pre-operative MRI (adjusted HR, 1.146; 95% CI, 0.278–4.724; P = 0.850). Conclusions Overall, MIS RH was associated with higher recurrence rates than open RH in patients with early-stage CC. However, MIS was not a poor prognostic factor among those with stage IB1 and cervical mass size ≤2 cm on pre-operative MRI. Highlights • We investigated survival outcome of radical hysterectomy (RH) by laparoscopic surgery in early-stage cervical cancer. • Compared to open RH, minimally invasive surgery (MIS) was associated with higher recurrence rates. • MIS RH was not a poor prognostic factor in patients with stage IB1 and cervical mass size ≤2 cm on pre-operative MRI. [ABSTRACT FROM AUTHOR]

Objectives: Preoperative cervical conization, while reducing the cervical mass size, might decrease the chance of tumor spillage during surgery. This study aimed to ascertain whether cervical conization before primary radical hysterectomy (RH) has a protective effect in patients with early cervical cancer. Methods: We retrospectively identified node-negative, marginnegative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who received primary Type C RH at two tertiary institutional hospitals between July 2006 and June 2020. Whether they received preoperative cervical conization or not, patients were divided into conization group (n =144) and control group (n =434). To adjust for confounders, we conducted a 1:1 propensity score matching for histology, surgical approach, lymphovascular space invasion, and cervical mass size (calculated by summing pathologic tumor size on conization and uterine specimens). Then, survival outcomes were compared between the matched groups. Results: Overall, the conization group had less cervical mass size and received minimally invasive surgery (MIS) more frequently (p =0.010) and adjuvant treatment less often (p =0.002) compared to the control group. Of 37 patients who received preoperative conization and had no residual tumor in the uterine specimen, only one (2.7%) recurred during 56.5 months of a median observation period. After matching, the conization group showed significantly better progression-free survival (PFS) than the control group (3-year: 94.2% vs 86.3%; p =0.012), whereas no significant difference in overall survival (OS) was found. Subgroup analysis in the open RH (n =91) revealed that PFS did not differ by preoperative conization (p =0.799). In contrast, in the MIS RH subgroup (n =197), preoperative conization was associated with significantly better PFS (p =0.005). Conclusions: Despite the retrospective design, our matched cohort study suggests that preoperative cervical conization might have a protective effect on disease recurrence in early cervical cancer, especially for those who are planning to undergo MIS RH. Further prospective studies are warranted. [ABSTRACT FROM AUTHOR]

We explored the prevalence of smoking, alcohol consumption, physical activity, and obesity in cervical cancer survivors and examined associations between sociodemographic factors and each health behavior. We studied 448 cervical cancer survivors ≥2 years after their initial diagnosis who had completed treatment. The total sample consisted of these survivors, and 4,480 cancer-free controls who were grouped into 5-year age cohorts and matched to the survivors in terms of both education and monthly household income. The prevalence of current smoking, current alcohol consumption, physical inactivity, and obesity in cervical cancer survivors (2.68, 23.88, 62.02, and 32.81%, respectively) did not differ significantly from those of matched non-cancer controls. Age (younger), marital status (married), and education (≥college) were associated with lower probabilities of current alcohol consumption (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.88–0.95; OR = 0.42, 95% CI = 0.23–0.78; OR = 0.49, 95% CI = 0.25–0.97, respectively). A monthly household income ≥$2,000, being employed, and self–rated health status (less healthy) were associated with physical inactivity (OR = 0.61, 95% CI = 0.37–0.99; OR = 2.16, 95% CI = 1.36–3.42; OR = 1.94, 95% CI = 1.23–3.05, respectively). Both age and number of years since diagnosis were associated with obesity (OR = 1.04, 95% CI = 1.01–1.08; OR = 0.38; 95% CI = 0.20–0.72, respectively). The health behaviors of cervical cancer survivors did not differ from those of matched cancer-free controls. As health behaviors are modifiable, identification of cervical cancer survivors who are at risk of an unhealthy lifestyle would allow individual- and population-based intervention programs to more effectively use their limited resources. [ABSTRACT FROM AUTHOR]

To determine whether prognostic impact of lymph node ratio (LNR), defined as the ratio between the number of positive lymph nodes and removed lymph nodes, is different by the surgical approach of radical hysterectomy (RH) in node-positive, early-stage cervical cancer. We retrospectively identified 2009 FIGO stage IB1-IIA2 patients who underwent primary Type C RH between 2010 and 2018 at two tertiary hospitals. Among them, only those with pathologically proven lymph node metastases and received adjuvant radiation therapy were included. Each patient's LNR was calculated, and its prognostic significance was investigated according to the two surgical approaches, open surgery, and minimally invasive surgery (MIS). In total, 55 patients were included in this analysis. All patients received concurrent chemoradiation therapy after surgery, and the median LNR (%) was 9.524 (range, 2.083-62.500). Based on receiver operating characteristic-curve analysis, the cut-off value for LNR (%) was determined as 8.831. Overall, patients with high LNR (≥8.831%; n=29) showed worse disease-free survival (DFS) than those with low LNR (<8.831%, n=26) (P=0.027), whereas no difference in overall survival was observed. Multivariate analyses adjusting clinicopathologic factors revealed that DFS was adversely affected by both MIS (HR, 8.132; P=0.038) and high LNR (HR, 10.837; P=0.045). In a subgroup of open RH, LNR was not associated with disease recurrence. However, in a subgroup of MIS, high LNR was identified as an independent poor prognostic factor for DFS (adjusted HR, 14.578; P=0.034). In patients with node-positive, early-stage cervical cancer, high LNR was associated with a significantly higher disease recurrence rate. This relationship was further consolidated among patients who received MIS RH. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of adjuvant radiotherapy (RT) on survival outcomes in patients with intermediate-risk, early-stage cervical cancer who underwent radical hysterectomy (RH). From the cervical cancer cohorts of two tertiary hospitals, patients with 2009 FIGO stage IB-IIA who underwent primary RH between 2010 and 2018 were identified. Patients with intermediate-risk factors that met the Sedlis criteria were included. Survival outcomes were compared between the patients who received adjuvant RT (study group; n=53) and those who did not receive adjuvant treatment (control group; n=30). Compared to the control group, the study group showed significantly better recurrence-free survival (RFS; 5-year survival rate, 85.6% vs. 61.0%; p=0.009). In multivariate analysis, adjuvant RT was associated with a significantly lower risk of disease recurrence (adjusted HR, 0.241; 95% CI, 0.082-0.709; p=0.010). In a subgroup that underwent open RH (n=33), adjuvant RT showed a trend toward improved RFS with borderline statistical significance (adjusted HR, 0.098; 95% CI, 0.009-1.027; p=0.053). However, in a subgroup of minimally invasive surgery (n=50), adjuvant RT did not improve RFS. In conclusion, the implementation of adjuvant RT significantly reduced the disease recurrence rate in patients with intermediate-risk, stage IB-IIA cervical cancer treated primarily with surgery. A survival benefit from adjuvant RT differed according to the surgical approach. [ABSTRACT FROM AUTHOR]

Simple Summary: An increased risk of relapse and death from minimally invasive radical hysterectomy has been reported in some patients with early cervical cancer. Thus, the development of an intuitive and precise decision-aid tool, which estimates recurrence and mortality rates by surgical approach, is necessary. To develop models predicting survival outcomes according to the surgical approach, we collected clinicopathologic and survival data of patients with 2009 FIGO stage IB cervical cancer who underwent a radical hysterectomy. Using only variables that could be obtained preoperatively, we developed various models predicting the probability of 5-year progression-free survival and overall survival. Among them, hybrid ensemble models, combined with logistic regression and multiple machine learning models, achieved the best predictive performance. The developed models are expected to help physicians' and patients' decision making related to the surgical approach for primary radical hysterectomy. We purposed to develop machine learning models predicting survival outcomes according to the surgical approach for radical hysterectomy (RH) in early cervical cancer. In total, 1056 patients with 2009 FIGO stage IB cervical cancer who underwent primary type C RH by either open or laparoscopic surgery were included in this multicenter retrospective study. The whole dataset consisting of patients' clinicopathologic data was split into training and test sets with a 4:1 ratio. Using the training set, we developed models predicting the probability of 5-year progression-free survival (PFS) and overall survival (OS) with tenfold cross validation. The developed models were validated in the test set. In terms of predictive performance, we measured the area under the receiver operating characteristic curve (AUC) values. The logistic regression models comprised of preoperative variables yielded AUCs of 0.679 and 0.715 for predicting 5-year PFS and OS rates, respectively. Combining both logistic regression and multiple machine learning models, we constructed hybrid ensemble models, and these models showed much improved predictive performance, with 0.741 and 0.759 AUCs for predicting 5-year PFS and OS rates, respectively. We successfully developed models predicting disease recurrence and mortality after primary RH in patients with early cervical cancer. As the predicted value is calculated based on the preoperative factors, such as the surgical approach, these ensemble models would be useful for making decisions when choosing between open or laparoscopic RH. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of adjuvant radiotherapy (RT) on survival outcomes in patients with intermediate-risk, early-stage cervical cancer who underwent radical hysterectomy (RH). From the cervical cancer cohorts of two tertiary hospitals, patients with 2009 FIGO stage IB-IIA who underwent primary RH between 2010 and 2018 were identified. Patients with intermediate-risk factors that met the Sedlis criteria were included. Survival outcomes were compared between the patients who received adjuvant RT (study group; n = 53) and those who did not receive adjuvant treatment (control group; n = 30). Compared to the control group, the study group showed significantly better recurrence-free survival (RFS; 5-year survival rate, 85.6% vs. 61.0%; p = 0.009). In multivariate analysis, adjuvant RT was associated with a significantly lower risk of disease recurrence (adjusted HR, 0.241; 95% CI, 0.082–0.709; p = 0.010). In a subgroup that underwent open RH (n = 33), adjuvant RT showed a trend toward improved RFS with borderline statistical significance (adjusted HR, 0.098; 95% CI, 0.009–1.027; p = 0.053). However, in a subgroup of minimally invasive surgery (n = 50), adjuvant RT did not improve RFS. In conclusion, implementation of adjuvant RT significantly reduced the disease recurrence rate in patients with intermediate-risk, stage IB-IIA cervical cancer treated primarily with surgery. Survival benefit from adjuvant RT differed according to the surgical approach. [ABSTRACT FROM AUTHOR]