Tumor size evaluated by pelvic examination compared with 3-D MR quantitative analysis in the prediction of outcome for cervical cancer☆

This study evaluated the safety and efficacy of carbon-ion radiation therapy (C-ion RT) with concurrent chemotherapy for locally advanced uterine cervical squamous cell carcinoma in a phase 1/2 clinical trial.

Twenty-two patients were treated with C-ion RT with concurrent weekly cisplatin at a dose of 40 mg/m². The phase 1 component evaluated the safety of 72.0 Gy (relative biological effectiveness) of C-ion RT with concurrent chemotherapy. In the phase 2 component, the safety and efficacy of C-ion RT with concurrent chemotherapy were assessed using the dose determined in phase 1.

The median follow-up period was 32 months, and the median tumor size was 71 mm (range, 51-150 mm). No patient had dose-limiting toxicities in the phase 1 component; the recommended dose was determined to be 72.0 Gy (relative biological effectiveness) with 40 mg/m² of cisplatin. In the phase 2 component, 2 patients developed grade 3 gastrointestinal tract toxicities. In patients treated with the recommended dose, the 2-year local control (LC), LC including salvage therapy, and overall survival rates were 67%, 81%, and 82%, respectively. The 2-year LC and overall survival rates for patients with tumor sizes ≤7.1 cm were 92% and 100%, respectively; for those with tumor sizes >7.1 cm they were 33% and 60%, respectively.

C-ion RT with concurrent weekly cisplatin was tolerated by patients with locally advanced uterine cervical squamous cell carcinoma. Outcomes were good in patients with tumor sizes ≤7.1 cm but not in those with larger tumors. The results of the present study should be validated with larger multi-institutional prospective studies. Further study is needed, and perhaps incorporating carbon ion external beam radiation with brachytherapy will further reduce the risk of central recurrence.

To quantify the gross tumor volume at diagnosis (GTV_D) and high-risk clinical target volume (CTV_HR) at brachytherapy (BT) and describe subgroups of patients with different patterns of response to chemoradiotherapy (CRT) in patients with FIGO stage IIB and IIIB cervical cancer treated with image-guided adaptive brachytherapy (IGABT). Additionally, to evaluate the feasibility of IGABT achieving adequate target coverage in these groups.

Patients with FIGO stage IIB and IIIB cervical cancer enrolled in the EMBRACE study were analyzed. T2-weighted MRI scans were obtained at diagnosis and at BT. GTV_D and CTV_HR were defined as per the GEC ESTRO recommendations. Patients were classified taking into account that initial tumor volume and response to CRT represented by the volume of residual disease (CTV_HR) and extent of residual parametrial disease are all major factors determining local dose delivery by BT, local control, and overall disease outcome. These factors were quantified applying the following criteria: (1) volume of the GTV_D relative to the median volume of the GTV_D; (2) the ratio (R) of CTV_HR to GTV_D for each patient; (3) the extent of residual parametrial disease at the time of BT. Accordingly, patients were classified into six groups (G1–G6): stage IB₁-like tumors (G1), tumors with good response and any size (G2), small tumors with moderate response (G3), large tumors with moderate response (G4), tumors with poor response (G5) and those with progressive disease (G6). Tumor and treatment characteristics were then compared among the first five groups (only 3 patients were allocated to G6).

A total of 481 patients were evaluated. The number of patients in the 6 groups were 55, 78, 123, 147, 75 and 3, respectively. The mean (SD) GTV_D was 43.6 (32.8) cm³ and the mean (SD) CTV_HR was 31.6 (16.1) cm³. The mean GTV_D and CTV_HR were 12.6 cm³ and 23.7 cm³ in G1 (R > 1.1), 47.5 cm³ and 25.3 cm³ in G2 (R < 0.9), 23.9 cm³ and 29.9 cm³ in G3 (R 0.9–1.1), 73.4 cm³ and 38.5 cm³ in G4 (R 0.9–1.1), 79.4 cm³ and 59.5 cm³ in G5 (R > 1.1), respectively. Parametrial disease extent at BT was as follows: no involvement in G1 and G2, proximal at most in G3 and G4, distal or to the pelvic wall in G5, progressive in G6. The use of interstitial needles was progressively higher among the groups (mean 0, 0, 2, 3, 6 in G1–5, P < 0.001). The mean GTV_BT D₁₀₀ in G1-5 was 103.1 Gy, 91.8 Gy, 93.5 Gy, 88.3 Gy and 87.1 Gy. The mean CTV_HR D₉₀ in G1-5 was 95.1 Gy, 92.1 Gy, 92.6 Gy, 87.6 Gy and 88.4 Gy.

In patients with FIGO stage IIB and IIIB disease, intra-FIGO stage heterogeneity and overlap between the two stages exist with respect to tumor volume, treatment response and extent of parametrial disease at BT. Taking into account GTV_D, parametrial disease at BT and the ratio of CTV_HR/GTV_D, five major groups exist. These enable prediction of GTV_BT and CTV_HR dose coverage through BT. IGABT, as performed in EMBRACE, accommodates to a considerable degree for the different variants of tumor regression in these groups through adaptation of the treatment technique including the use of needles. However, major variations remain at present with regard to dose to GTV_BT and to CTV_HR, which are most pronounced in G4 and G5. This new classification will be validated in future in regard to clinical outcome in EMBRACE.

Resection of brain tumors is a tricky task in surgery due to its direct influence on the patients’ survival rate. Determining the tumor resection extent for its complete information via-à-vis volume and dimensions in pre- and post-operative Magnetic Resonance Images (MRI) requires accurate estimation and comparison. The active contour segmentation technique is used to segment brain tumors on pre-operative MR images using self-developed software. Tumor volume is acquired from its contours via alpha shape theory. The graphical user interface is developed for rendering, visualizing and estimating the volume of a brain tumor. Internet Brain Segmentation Repository dataset (IBSR) is employed to analyze and determine the repeatability and reproducibility of tumor volume. Accuracy of the method is validated by comparing the estimated volume using the proposed method with that of gold-standard. Segmentation by active contour technique is found to be capable of detecting the brain tumor boundaries. Furthermore, the volume description and visualization enable an interactive examination of tumor tissue and its surrounding. Admirable features of our results demonstrate that alpha shape theory in comparison to other existing standard methods is superior for precise volumetric measurement of tumor.

To classify tumor imaging voxels at-risk for treatment failure within the heterogeneous cervical cancer using DCE MRI and determine optimal voxel's DCE threshold values at different treatment time points for early prediction of treatment failure.

DCE-MRI from 102 patients with stage IB2–IVB cervical cancer was obtained at 3 different treatment time points: before (MRI 1) and during treatment (MRI 2 at 2–2.5 weeks and MRI 3 at 4–5 weeks). For each tumor voxel, the plateau signal intensity (SI) was derived from its time-SI curve from the DCE MRI. The optimal SI thresholds to classify the at-risk tumor voxels was determined by the maximal area under the curve using ROC analysis when varies SI value from 1.0 to 3.0 and correlates with treatment outcome.

The optimal SI thresholds for MRI 1, 2 and 3 were 2.2, 2.2 and 2.1 for significant differentiation between local recurrence/control, respectively, and 1.8, 2.1 and 2.2 for death/survival, respectively.

Optimal SI thresholds are clinically validated to quantify at-risk tumor voxels which vary with time. A single universal threshold (SI = 1.9) was identified for all 3 treatment time points and remained significant for the early prediction of treatment failure.

The authors performed phase I/II clinical trial to evaluate the toxicity and efficacy of carbon ion radiotherapy (C-ion RT) for locally advanced squamous cell carcinoma of the uterine cervix.

Between April 2000 and January 2006, 22 patients for Protocol 9902 were treated with C-ion RT. The number of patients with stage IIB, IIIB, and IVA diseases was 1, 18, and 3, respectively. All patients had bulky tumors measuring 4.0–12.0 cm (median 6.2 cm). The whole pelvic dose was fixed at 39.0 GyE for 13 fractions, and additional 15.0 GyE for 5 fractions was given to the gross tumor volume (GTV) and surrounding tissues. With regard to local boost, a dose–escalation study was planned for 2 fractions to GTV. Total dose to the cervical tumor was 64.0–72.0 GyE for 20 fractions.

All patients completed the scheduled therapy and no patient developed Grade 2 or higher acute toxicity. There was no Grade 3 or higher late complications at each dose. The 5-year overall survival rate and local control rate were 50.0% and 68.2%, respectively. Seven out of the 16 patients who received 64.0–68.0 GyE developed local recurrences, but all patients who received 72.0 GyE maintained local control.

There were no severe acute or late complications in this trial. C-ion RT has the potential to improve the treatment for locally advanced bulky cervical cancer by applying a total dose of 72.0 GyE, with the results lending incentive to further investigations to confirm the therapeutic efficacy.

Although serum carcinoembryonic antigen (CEA) levels reflect tumor volume in rectal cancer patients intrapersonally, it is unclear interpersonally. We determined the correlation between pretreatment serum CEA levels and tumor volume.

A total of 489 patients with locally advanced primary rectal cancer who underwent preoperative chemoradiotherapy followed by surgery between October 2001 and April 2007 were retrospectively evaluated. CEA levels were measured by chemiluminescent microparticle immunoassay, and magnetic resonance (MR) volumetry was performed using MR data. The correlation between CEA levels and tumor volume was assessed using linear regression analysis and one-way analysis of variance. The prognostic values of CEA levels and tumor volume for survival were evaluated.

There was no significant correlation between CEA levels and tumor volume. The five-year overall survival and disease-free survival were 89.0%, 80.6% and 82.9%, and 72.0%, 70.0% and 60.3% in patients with CEA levels of ≤ 3 ng/ml, > 3–10 ng/ml, and > 10 ng/ml, respectively. Tumor volume had no prognostic value for either overall survival or disease-free survival

Pretreatment serum CEA levels were not correlated with tumor volume. While there was no correlation between tumor volume and survival, there was a positive correlation between CEA levels and survival.