Seung-Gu Yeo

Tumor Volume Reduction Rate Measured by Magnetic Resonance Volumetry Correlated With Pathologic Tumor Response of Preoperative Chemoradiotherapy for Rectal Cancer

PURPOSE To determine whether the tumor volume reduction rate (TVRR) measured using three-dimensional region-of-interest magnetic resonance volumetry correlates with the pathologic tumor response after preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. METHODS AND MATERIALS The study included 405 patients with locally advanced rectal cancer (cT3-T4) who had undergone preoperative CRT and radical proctectomy. The tumor volume was measured using three-dimensional region-of-interest magnetic resonance volumetry before and after CRT but before surgery. We analyzed the correlation between the TVRR and the pathologic tumor response in terms of downstaging and tumor regression grade (TRG). Downstaging was defined as ypStage 0-I (ypT0-T2N0M0), and the TRG proposed by Dworak et al. was used. RESULTS The mean TVRR was 65.0% +/- 22.3%. Downstaging and complete regression occurred in 167 (41.2%) and 58 (14.3%) patients, respectively. The TVRRs according to ypT classification (ypT0-T2 vs. ypT3-T4), ypN classification (ypN0 vs. ypN1-N2), downstaging (ypStage 0-I vs. ypStage II-III), good regression (TRG 3-4 vs. TRG 1-2), and complete regression (TRG 4 vs. TRG 1-3) were all significantly different (p <.05). When the TVRR was categorized into three groups (<60%, 60-80%, and >80%), the rates of ypT0-T2, ypN0, downstaging, and good regression were all significantly greater for patients with a TVRR of >or=60%, as was the complete regression rate for patients with a TVRR >80% (p <.05). CONCLUSION The TVRR measured using three-dimensional region-of-interest magnetic resonance volumetry correlated significantly with the pathologic tumor response in terms of downstaging and TRG after preoperative CRT for locally advanced rectal cancer.

Tumor Volume Reduction Rate After Preoperative Chemoradiotherapy as a Prognostic Factor in Locally Advanced Rectal Cancer

PURPOSE To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). METHODS AND MATERIALS In total, 430 primary LARC (cT3-4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume--post-CRT tumor volume) × 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27-99 months) for survivors. Endpoints were disease-free survival (DFS) and overall survival (OS). RESULTS The median TVRR was 70.2% (mean, 64.7% ± 22.6%; range, 0-100%). Downstaging (ypT0-2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS. CONCLUSIONS Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT.

Interstitial Fluid Pressure as a Prognostic Factor in Cervical Cancer Following Radiation Therapy

Purpose: To investigate tumor interstitial fluid pressure as a prognostic factor for recurrence-free survival in patients with cervical cancer following radiation therapy. Experimental Design: Tumor interstitial fluid pressure was measured in 55 cervical cancer patients who received radiation therapy between August 1998 and September 2002. Interstitial fluid pressure measurements were made before radiation therapy (pre–radiation therapy interstitial fluid pressure) and after a median of 28.8 Gy in 16 fractions (range, 25.2-30.6 Gy in 14-17 fractions) of radiation therapy (mid–radiation therapy interstitial fluid pressure), using a modified wick-in-needle technique. Median follow-up was 74 months (range, 2-118 months). The Kaplan-Meier method with the log-rank test and Coxs proportional hazard model were used in univariate and multivariate analyses, respectively, of prognostic factors for recurrence-free survival. Results: Median pre–radiation therapy and mid–radiation therapy interstitial fluid pressure were 29.0 mm Hg (range, 4.0-93.9 mm Hg) and 20.0 mm Hg (range, −1.2 to 29.6 mm Hg), respectively (P = 0.001). Pre–radiation therapy interstitial fluid pressure was significantly higher in adenocarcinomas than squamous cell carcinomas (P = 0.028). Significant reduction of interstitial fluid pressure was noted only in patients with complete responses (P = 0.002), and mid–radiation therapy interstitial fluid pressure was significantly lower in patients with complete responses (P = 0.036). In the multivariate analysis including interstitial fluid pressures and clinical variables, pre–radiation therapy interstitial fluid pressure was an independent prognostic factor for local and distant recurrence-free survival (P = 0.001 and 0.027, respectively). Conclusions: Mid–radiation therapy interstitial fluid pressure measurement may be useful in predicting radiation therapy responses, and pre–radiation therapy interstitial fluid pressure was a significant prognostic factor for local and distant relapse-free survival in patients with cervical cancer after radiation therapy. (Clin Cancer Res 2009;15(19):6201–7)

Accelerated partial breast irradiation using multicatheter brachytherapy for select early-stage breast cancer: local control and toxicity

BackgroundTo investigate the efficacy and safety of accelerated partial breast irradiation (APBI) via high-dose-rate (HDR) multicatheter interstitial brachytherapy for early-stage breast cancer.MethodsBetween 2002 and 2006, 48 prospectively selected patients with early-stage breast cancer received APBI using multicatheter brachytherapy following breast-conserving surgery. Their median age was 52 years (range 36-78). A median of 34 Gy (range 30-34) in 10 fractions given twice daily within 5 days was delivered to the tumor bed plus a 1-2 cm margin. Most (92%) patients received adjuvant systemic treatments. The median follow-up was 53 months (range 36-95). Actuarial local control rate was estimated from surgery using Kaplan-Meier method.ResultsLocal recurrence occurred in two patients. Both were true recurrence/marginal miss and developed in patients with close (< 0.2 cm) surgical margin after 33 and 40 months. The 5-year actuarial local recurrence rate was 4.6%. No regional or distant relapse and death has occurred to date. Late Grade 1 or 2 late skin and subcutaneous toxicity was seen in 11 (22.9%) and 26 (54.2%) patients, respectively. The volumes receiving 100% and 150% of the prescribed dose were significantly higher in the patients with late subcutaneous toxicity (p = 0.018 and 0.034, respectively). Cosmesis was excellent to good in 89.6%.ConclusionsAPBI using HDR multicatheter brachytherapy yielded local control, toxicity, and cosmesis comparable to those of conventional whole breast irradiation for select early-stage breast cancer. Patients with close resection margins may be ineligible for APBI.

Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

PURPOSE A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. METHODS AND MATERIALS Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m(2)/day) and leucovorin (20 mg/m(2)/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologic downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. RESULTS Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. CONCLUSIONS Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique.

Local Excision Following Pre-operative Chemoradiotherapy-induced Downstaging for Selected cT3 Distal Rectal Cancer

OBJECTIVE To investigate the long-term outcomes of selected patients with cT3 distal rectal cancer treated with local excision following pre-operative chemoradiotherapy. METHODS Between January 2003 and February 2008, 11 patients with cT3 distal rectal cancer received a local excision following pre-operative chemoradiotherapy. The median age of the patients was 61 years (range, 42-71). The median tumor size was 3 cm (range, 2-5), and the median distance of the caudal tumor edge from the anal verge was 3 cm (range, 1-4). Clinical lymph node status was positive in five patients. Pre-operative chemoradiotherapy consisted of a 50.4 Gy in 28 fractions with concurrent chemotherapy. A transanal full-thickness local excision was performed after a median of 54 days (range, 31-90) from chemoradiotherapy completion. Ten patients received post-operative chemotherapy. RESULTS Pathologically complete responses occurred in eight patients, ypT1 in two and ypT2 in one. The pathologic tumor size for three ypT1-2 tumors was 0.9, 1.1 and 2.2 cm. The follow-up period was a median of 59 months (range, 24-85). One patient (ypT0) developed recurrence at the excision site 14 months after surgery, but was successfully salvaged with an abdominoperineal resection and adjuvant chemotherapy. Another patient (ypT2) developed bone metastasis after 8 months and died of the disease. The 5-year local recurrence-free, disease-free and overall survival rates were 90.9%, 81.8% and 88.9%, respectively. No Grade 3 or worse gastrointestinal toxicity was detected. CONCLUSIONS Full-thickness local excision following chemoradiotherapy may be an acceptable option for cT3 distal rectal cancer that responds well to chemoradiotherapy.

Patterns of failure in patients with locally advanced rectal cancer receiving pre-operative or post-operative chemoradiotherapy

BackgroundWe investigated patterns of failure in patients with locally advanced rectal cancer (LARC) according to chemoradiotherapy (CRT) timing: pre-operative versus post-operative. Also, patterns of failure, particularly distant metastasis (DM), were analyzed according to tumor location within the rectum.MethodsIn total, 872 patients with LARC who had undergone concurrent CRT and radical surgery between 2001 and 2007 were analyzed retrospectively. Concurrent CRT was administered pre-operatively (cT3–4) or post-operatively (pT3–4 or pN+) in 550 (63.1%) and 322 (36.9%) patients, respectively. Median follow-up period was 86 (range, 12–133) months for 673 living patients. Local recurrence (LR) was defined as any disease recurrence within the pelvis, and any failure outside the pelvis was classified as a DM. Only the first site of recurrence was scored.ResultsIn total, 226 (25.9%) patients developed disease recurrence. In the pre-operative CRT group, the incidences of isolated LR, combined LR and DM, and isolated DM were 17, 21, and 89 patients, respectively. In the post-operative CRT group, these incidences were 8, 15, and 76 patients, respectively. LR within 2 years constituted 44.7% and 60.9% of all LRs in the pre-operative and post-operative CRT groups, respectively. Late (> 5 years) LR comprised 13.2% and 4.3% of all LRs in the pre-operative and post-operative CRT groups, respectively. The lung was the most common DM site (108/249, 43.4%). Lung or para-aortic lymph node metastasis developed more commonly from low-to-mid rectal tumors while liver metastasis developed more commonly from upper rectal tumors. Lung metastasis occurred later than liver metastasis (n = 54; 22.6 ± 15.6 vs. 17.4 ± 12.1 months; P = 0.035).ConclusionsThis study showed that LARC patients receiving pre-operative CRT tended to develop late LR more often than those receiving post-operative CRT. Further extended follow-up than is conventional may be necessary in LARC patients who are managed with optimized multimodal treatments, and the follow-up strategy may need to be individualized according to tumor location within the rectum.

Reappraisal of pretreatment carcinoembryonic antigen in patients with rectal cancer receiving preoperative chemoradiotherapy.

AIMS AND BACKGROUND The pretreatment serum carcinoembryonic antigen (CEA) level is an independent prognostic factor in colorectal cancer. We aimed to investigate the significance of CEA as a prognostic or predictive factor in rectal cancer patients receiving preoperative chemoradiotherapy (CRT). METHODS AND STUDY DESIGN In total, 609 patients with locally advanced (cStage II-III) mid to distal rectal cancer who underwent preoperative CRT and radical surgery between 2001 and 2008 were analyzed retrospectively. Predictive factors for pathologic CRT response were determined using multivariate logistic regression. A prognostic factor analysis was performed using the log-rank test and Cox proportional hazards regression. RESULTS Elevated CEA levels (>5 ng/mL) were observed in 201 (33.0%) patients at diagnosis. Following preoperative CRT, downstaging (ypStage 0-I) occurred in 255 (41.9%) patients, of whom 88 had pathologic complete tumor regression. Pretreatment CEA was significantly associated with pathologic CRT response in terms of downstaging and tumor regression grade, and was the most relevant predictive factor. After a median follow-up period of 60 months, the 5-year disease-free and overall survival rates were 76.2% and 84.6%, respectively. Prognostic factors independently associated with recurrence or survival included ypStage, circumferential resection margin, and histologic grade. CONCLUSIONS In patients with rectal cancer who received preoperative CRT, the pretreatment CEA level was a significant and independent predictor of pathologic CRT response. However, it may not be able to predict long-term outcomes independently of ypStage.

Curative chemoradiotherapy for isolated retroperitoneal lymph node recurrence of colorectal cancer

PURPOSE To investigate the efficacy of curative chemoradiotherapy for isolated retroperitoneal lymph node recurrence of colorectal cancer. MATERIALS AND METHODS Twenty-two colorectal cancer patients who received three-dimensional conformal radiotherapy (n=20) or helical tomotherapy (n=2) for isolated retroperitoneal lymph node recurrence were analyzed retrospectively. Radiation dose was 55.8Gy in 31 fractions or 63Gy in 35 fractions, and 60Gy in 20 fractions by helical tomotherapy. All patients received concurrent chemotherapy and 16 (72.7%) received adjuvant chemotherapy. RESULTS The treatment response was complete in 13 (59.1%), partial in 6 (27.3%), and stable in 3 (13.6%) patients. Median follow-up for 11 (50%) surviving patients was 32 months (range, 27-61). The 3- and 5-year overall survival rates were 64.7% and 36.4%, and median overall survival was 41 months. Recurrences developed in 15 (68.2%) patients; outside the retroperitoneum in 13. The 3- and 5-year recurrence-free survival rates were 34.1% and 25.6%, and median recurrence-free survival was 20 months. Response and adjuvant chemotherapy were significant prognostic factors for overall survival. Gastrointestinal toxicity ≥ Grade 3 was not observed. CONCLUSIONS Definitive chemoradiotherapy is an effective salvage treatment for isolated retroperitoneal lymph node recurrence of colorectal cancer without severe complications.

Efficient approach for determining four-dimensional computed tomography-based internal target volume in stereotactic radiotherapy of lung cancer.

Purpose This study aimed to investigate efficient approaches for determining internal target volume (ITV) from four-dimensional computed tomography (4D CT) images used in stereotactic body radiotherapy (SBRT) for patients with early-stage non-small cell lung cancer (NSCLC). Materials and Methods 4D CT images were analyzed for 15 patients who received SBRT for stage I NSCLC. Three different ITVs were determined as follows: combining clinical target volume (CTV) from all 10 respiratory phases (ITV10Phases); combining CTV from four respiratory phases, including two extreme phases (0% and 50%) plus two intermediate phases (20% and 70%) (ITV4Phases); and combining CTV from two extreme phases (ITV2Phases). The matching index (MI) of ITV4Phases and ITV2Phases was defined as the ratio of ITV4Phases and ITV2Phases, respectively, to the ITV10Phases. The tumor motion index (TMI) was defined as the ratio of ITV10Phases to CTVmean, which was the mean of 10 CTVs delineated on 10 respiratory phases. Results The ITVs were significantly different in the order of ITV10Phases, ITV4Phases, and ITV2Phases (all p < 0.05). The MI of ITV4Phases was significantly higher than that of ITV2Phases (p < 0.001). The MI of ITV4Phases was inversely related to TMI (r = -0.569, p = 0.034). In a subgroup with low TMI (n = 7), ITV4Phases was not statistically different from ITV10Phases (p = 0.192) and its MI was significantly higher than that of ITV2Phases (p = 0.016). Conclusion The ITV4Phases may be an efficient approach alternative to optimal ITV10Phases in SBRT for early-stage NSCLC with less tumor motion.