Yoo-Kang Kwak

Timely tumor response analysis after preoperative chemoradiotherapy and curative surgery in locally advanced rectal cancer: A multi-institutional study for optimal surgical timing in rectal cancer

BACKGROUND AND PURPOSE The definite surgical timing in rectal cancer after preoperative chemoradiotherapy (CRT) has not yet been fully examined. We assess the tumor response and identify the optimal operation timing after preoperative CRT in rectal cancer. METHODS AND MATERIALS The study included data of 1786 patients with locally advanced rectal cancer (cT3-4N0-2M0). They received preoperative CRT followed by total mesorectal excision. Total radiation dose was 50.4Gy in 28 fractions. Interval time between preoperative CRT and surgery ranged from 2 to 26weeks, with a median interval of 7.2weeks. Primary endpoint was to evaluate the period of highest downstaging and pathological complete response (ypCR) rates to determine the optimal timing for curative surgery after CRT. RESULTS Downstaging rates peaked between 6 and 7weeks after CRT and declined afterward. ypCR rates increased from 5 to 6weeks after CRT and decreased after 9 to 10weeks. Downstaging rates were similar between the two arms showing 36.9% in the early arm (⩽7weeks) and 37.0% in the delayed arm (>7weeks). ypCR rates were significantly higher in the delayed arm, as compared to the early arm (12.3% vs. 8.6%, p=0.011). The delayed arm had higher sphincter preservation rates than the early arm with a marginal significance (92.4% vs. 89.9%, p=0.078). There was no statistically significant difference regarding relapse-free survival and overall survival between the two arms. CONCLUSIONS ypCR rates increased after 5weeks and decreased after 10weeks and the delayed (>7weeks after CRT) group showed significantly increased ypCR rates than the early arm (⩽7weeks after CR). The optimal timing for curative surgery in rectal cancer when tumor response is maximal is after 7weeks and before 10weeks following preoperative CRT.

Interpretation and Prognostic Value of Positron Emission Tomography-Computed Tomography After Induction Chemotherapy With or Without Radiation in IIIA-N2 Non-small Cell Lung Cancer Patients Who Receive Curative Surgery

AbstractWe evaluate the correlation of clinical staging on positron emission tomography-computed tomography (PET-CT) and pathologic staging and the prognostic value of PET-CT after induction chemotherapy in patients with locally advanced nonsmall cell lung cancer (NSCLC).We analyzed 42 cases of clinical stage IIIA-N2 NSCLC who receive 2 to 4 cycles of preoperative chemotherapy with or without radiation followed by curative resection. The maximum standard uptake value (SUVmax) of the suspected lesion on PET-CT was recorded. PET-CT findings after induction chemotherapy were compared with those of initial PET-CT and pathology after surgery.The accuracy of PET-CT in restaging of the primary tumor after induction chemotherapy was 50.0%. Eighteen (42.8%) of 42 patients were underestimated ycT stage, and 3 (7.1%) of 42 patients was overestimated ycT stage by PET-CT scan. The accuracy of PET-CT in restaging of the nodal disease was 71.4%. Six (14.3%) of 42 patients were underestimated ycN stage, and 6 (14.3%) of 42 patients were overestimated ycN stage as compared with pathologic staging. The 2-year overall survival (OS) and relapse-free survival (RFS) rate were 68.5% and 40.9%, respectively. Complete responders (ycT0N0M0) on PET-CT after induction chemotherapy had a significantly longer RFS time than did incomplete responders (28.3 vs 9.1 months, P = 0.021).Complete response on PET-CT after induction chemotherapy with or without radiation was a good prognosticator for RFS in stage IIIA-N2 NSCLC patients who received surgery. However, response evaluation on PET-CT after induction chemotherapy should be interpreted with caution due to its unacceptable accuracy.

Displacement of Surgical Clips during Postoperative Radiotherapy in Breast Cancer Patients Who Received Breast-Conserving Surgery.

Purpose Surgical clips are used as a target for postoperative breast radiotherapy, and displacement of surgical clips would result in inaccurate delivery of radiation. We investigated the displacement range of surgical clips in the breast during postoperative radiotherapy following breast-conserving surgery. Methods A total of 178 patients who received breast-conserving surgery and postoperative radiation of 59.4 Gy in 33 fractions to the involved breast for 6.5 weeks were included. Surgical clips were used to mark the lumpectomy cavity during breast-conserving surgery. Patients undertook planning computed tomography (CT) scan for whole breast irradiation. Five weeks after beginning radiation, when the irradiation dose was 45 Gy, planning CT scan was performed again for a boost radiotherapy plan in all patients. The surgical clips were defined in both CT images and compared in lateromedial (X), anteroposterior (Y), superoinferior (Z), and three-dimensional directions. Results The 90th percentile of displacement of surgical clips was 5.31 mm (range, 0.0–22.2 mm) in the lateromedial direction, 7.1 mm (range, 0.0–14.2 mm) in the anteroposterior direction, and 6.0 mm (range, 0.0–10.0 mm) in the superoinferior direction. The 90th percentile of three-dimensional displacement distance was 9.8 mm (range, 0.0–28.2 mm). On the multivariate analysis, seroma ≥15 mL was the only independent factor associated with the displacement of surgical clips. In patients with seroma ≥15 mL, the 90th percentile of displacement of surgical clips was 15.1 mm in the lateromedial direction, 12.7 mm in the anteroposterior direction, 10.0 mm in the superoinferior direction, and 21.8 mm in the three-dimensional distance. Conclusion A target volume expansion of 10 mm from surgical clips may be sufficient to compensate for the displacement of clips during postoperative radiotherapy after breast-conserving surgery. For patients who had a seroma, a replanning CT scan for a boost radiation should be considered to ensure exact postoperative radiotherapy in breast cancer.

Intensity-modulated radiotherapy reduces gastrointestinal toxicity in pelvic radiation therapy with moderate dose

This retrospective study was performed to evaluate and compare gastrointestinal (GI) toxicities caused by conventional radiotherapy (cRT) and intensity modulated radiotherapy (IMRT) in 136 cancer patients treated with pelvic radiotherapy (RT) with moderate radiation dose in a single institution. A matched-pair analysis of the two groups was performed; each group included 68 patients. Conventional RT was delivered using the four-field box technique and IMRT was delivered with helical tomotherapy. The median daily dose was 1.8 Gy and the median total dose was 50.4 Gy (range 25.2–56 Gy). Primary end point was GI toxicity during and after RT. Secondary end point was factors that affect toxicity. Patients treated with IMRT had lower incidence of grade ≥ 2 acute GI toxicity compared to the patients treated with cRT (p = 0.003). The difference remained significant in multivariate analysis (p = 0.01). The incidence of chronic GI toxicity was not statistically different between the two groups, but the cRT group had higher incidence of grade 3 chronic GI toxicity. Based on our results, IMRT can reduce GI toxicity compared to cRT in the treatment of pelvic radiotherapy even with moderate radiation dose and this will enhance patients’ quality of life and treatment compliance.

Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

Purpose Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Materials and Methods Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. Results With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Conclusion Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

Lymphovascular Invasion Increases the Risk of Nodal and Distant Recurrence in Node-Negative Stage I–IIA Non-Small-Cell Lung Cancer

Objectives: Despite complete surgical resection, 30–40% of patients with stage I–IIA non-small-cell lung cancer (NSCLC) have recurrences. We aimed to elucidate the effect of lymphovascular invasion (LVI) on the prognosis and patterns of recurrence in patients with pathologically confirmed T1–2N0 NSCLC. Methods: We evaluated 381 patients who underwent complete resection and were diagnosed with pathologic T1–2N0 NSCLC between March 2000 and January 2012. Local recurrence, nodal recurrence, and distant metastasis were defined and analyzed. Results: LVI was present in 72 patients (18.9%). The 5-year disease-free survival (DFS) for all patients was 69.9%. Patients with LVI showed a significant decrease in 5-year DFS (47.3 vs. 74.4%, p < 0.001). LVI was a significant prognostic predictor in multivariate analysis (p = 0.003). The patients with LVI showed a significantly increased 5-year cumulative incidence of nodal recurrence (22.5 vs. 8.7%, p < 0.001) and distant metastasis (30.4 vs. 14.9%, p = 0.004). However, no difference was shown between the two groups in the 5-year cumulative incidence of local recurrence (p = 0.416). Conclusions: LVI is a negative prognostic factor in patients with stage I–IIA NSCLC. The presence of LVI significantly increases the risk of nodal and distant recurrence.

Radiotherapy as an alternative treatment option for primary central nervous system lymphoma patients who are noncandidates for chemotherapy

The standard treatment for primary central nervous system (CNS) lymphoma is based on chemotherapy. However, there are patients who are not indicated for chemotherapy and when left untreated, the expected functional outcomes for these patients are devastating since the disease causes various neurologic symptoms. Therefore, we assessed the effects of radiotherapy as an alternative therapy in primary CNS lymphoma. Thirty-two patients were diagnosed with primary CNS lymphoma and treated with radiotherapy alone. Patients received whole brain radiotherapy (WBRT) to a median dose of 30 Gy (range, 14.4–50 Gy) and the median total radiotherapy dose was 50 Gy (range, 30–54 Gy). The status on neurologic symptoms before and after radiotherapy was inquired during the regular follow-ups. The progression-free survival (PFS) and overall survival (OS) rates for the enrolled patients were calculated. The median follow-up time was 21 months. All but one of the patients presented with neurologic symptoms. The most common symptoms were hemiparesis and headache. After radiotherapy, these symptoms were relieved in 27 patients (84.4%). The median PFS and OS rates were 15.8 and 16.3 months, respectively. Twenty patients (62.5%) experienced recurrent disease at follow up and among them, fifteen patients (46.9%) had intracranial recurrence. The median intracranial PFS was 19.3 months. Untreated primary CNS lymphoma causes neurologic deficits and the survival after only supportive care is poor. Therefore, when chemotherapy is unfeasible, an alternative treatment should be applied and radiotherapy can be a practical option.

Treatment outcome of diffuse large B-cell lymphoma involving the head and neck: Two-institutional study for the significance of radiotherapy after R-CHOP chemotherapy

Abstract This study was performed to analyze the treatment outcome for diffuse large B-cell lymphoma (DLBCL) involving the head and neck and to evaluate the role of radiotherapy in the rituximab era. Fifty-six patients diagnosed with DLBCL involving the head and neck were assessed. All patients were treated with 6 cycles of rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone (R-CHOP). After chemotherapy, radiation was delivered to the head and neck area in a median dose of 36 Gy. Radiation was delivered using 3-dimensional radiotherapy (n  =  25) or intensity-modulated radiotherapy (n  =  31). Primary endpoints were relapse-free survival (RFS), overall survival (OS), and local control rate. After median follow-up time of 45 months, the 5-year RFS and OS rates were 72% and 61%, respectively. Fourteen (25%) of 56 patients relapsed; 1 had a local relapse, 11 had distant relapses, and 2 had both local and distant relapses. The final local control rate after radiotherapy was 94%. Age, performance status, international prognostic index score, and radiotherapy response were significant prognostic factors for both RFS and OS in the multivariate analysis. Incidence of acute grade 3 and 4 hematologic toxicity was 9% and 4%, respectively. Grade 3 nonhematologic toxicity occurred in 2 (4%) patients, and there was no grade 4 nonhematologic toxicity for the irradiated patients. Excellent local control and survival rates can be achieved with R-CHOP followed by radiotherapy in patients with DLBCL involving the head and neck. Treatment-related toxicity after the introduction of modern radiotherapy was acceptable and limited.