Ruthenium-106 Brachytherapy with or without Additional Local Therapy Shows Favorable Outcome for Variable-Sized Choroidal Melanomas in Korean Patients.

PURPOSE: The purpose of this study was to report clinical outcomes of ruthenium-106 (106Ru) brachytherapy with or without additional local therapy for choroidal melanomas in Korean patients. MATERIALS AND METHODS: A total of 88 patients diagnosed with choroidal melanomas were treated with 106Ru brachytherapy between 2006 and 2012. Patients were divided into two groups according to their tumor height: a large group (≥ 6 mm, n=50) and a small group (< 6 mm, n=38). Most patients in the large group received combined therapy with local excision and/or transpupillary thermotherapy. In general, 85-95 Gy was administered to the apex of the tumor, while 100 Gy was administered to the point 2-6 mm from the outer surface of the sclera for patients undergoing combined therapy. RESULTS: The median follow-up duration was 30 months. The 3-year local control rate was significantly higher in the small group than in the large group (94% vs. 70%, p=0.047). The free from distant metastasis (FFDM) rate and the overall survival (OS) rate were also higher in patients in the small group (3-year FFDM, 97% vs. 76%; p=0.031 and 3-year OS, 97% vs. 72%; p=0.036). A total of 13 patients underwent enucleation. The eye-preservation rate was also higher in the small group (3-year eye-preservation rate, 94% vs. 70%; p=0.050), and tumor height was a significant prognostic factor for eye-preservation. CONCLUSION: 106Ru brachytherapy showed favorable outcomes in small choroidal melanomas in Korean patients. Although additional local treatment could improve eye-preservation rate for large tumors, other strategies should be considered for disease control.

A Randomized Phase 2 Study of Neoadjuvant Chemoradiaton Therapy With 5-Fluorouracil/Leucovorin or Irinotecan/S-1 in Patients With Locally Advanced Rectal Cancer.

PURPOSE: The purpose of this study was to evaluate the rate of pathologic complete response (pCR) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation therapy (CRT) with leucovorin (FL) versus irinotecan/S-1 (IS). METHODS AND MATERIALS: Patients with resectable LARC (clinical stage T3/4, lymph node positive, or both) were randomly assigned to receive preoperative radiation (45-50.4 Gy in 25 to 28 daily fractions) and concomitant chemotherapy either with a bolus injection of FL (400 mg/m(2)/day 5-fluorouracil and 20 mg/m(2)/day leucovorin) for 3 consecutive days every 4 weeks for 2 cycles (FL group) or with 40 mg/m(2) irinotecan on days 1, 8, 15, 22, and 29, and 35 mg/m(2) S-1 twice on the day of irradiation (IS group). Curative surgery was performed approximately 4 to 8 weeks after the completion of CRT. The postoperative chemotherapy regimen was FL with a primary endpoint of a pCR rate evaluation. RESULTS: One hundred forty-two eligible patients were randomly assigned, and the median follow-up duration was 43.8 months (95% confidence interval, 40.8-46.8 months). One hundred thirty-three patients (93.7%) of 142 underwent total mesorectal excision; pCR was achieved in 11 (16.7%) of 66 patients in the FL group and 17 (25.8%) of 67 patients in the IS group (P=.246). When good responders were defined as patients with Mandard grades 1 and 2, the rate of good responders was significantly higher in the IS group than in the FL group (54.6% vs 36.4%, respectively, P=.036). The preoperative rates of grade 3 and 4 toxicities were higher in the IS group (7.0%) than in the FL group (1.4%, P=.095). The 3-year disease-free survival was not significantly different between the 2 groups (79.7% vs 76.6%, respectively, P=.896). CONCLUSIONS: IS-based preoperative CRT did not increase pCR rate, but it did increase acute toxicities compared with standard 5-FU treatment. Therefore, further investigation is needed.

Association Between Choroidal Thickness and Metabolic Activity on Positron Emission Tomography in Eyes With Choroidal Melanoma.

PURPOSE: To investigate the relationship between subfoveal choroidal thickness and metabolic activity in eyes with choroidal melanoma. DESIGN: Retrospective, interventional case series. METHODS: The medical records of 16 patients with unilateral choroidal melanoma who underwent ruthenium (Ru) 106 brachytherapy with adjuvant transpupillary thermotherapy and who had available pretreatment positron emission tomography-computed tomography (PET-CT) images were retrospectively reviewed. Subfoveal choroidal thickness was measured in tumor eyes and in unaffected fellow eyes using enhanced-depth imaging spectral-domain optical coherence tomography (EDI OCT). Tumor eyes were divided into 2 groups (metabolically active and inactive) based on PET-CT findings and subfoveal choroidal thickness was compared between groups. Additionally, choroidal thickness measurements were compared before and after treatment. RESULTS: Before treatment, mean choroidal thickness was 293.31 ± 46.80 µm in tumor eyes and 242.44 ± 65.37 µm in fellow eyes, a difference that was statistically significant (P = .003). Eyes with metabolically active tumors had a significantly thicker choroid (348.00 ± 17.32 µm) than eyes with metabolically inactive tumors (280.69 ± 42.04 µm, P = .019). In tumor eyes, mean choroidal thickness significantly decreased from pretreatment values to 253.56 ± 61.27 µm 6 months after treatment (P = .018). CONCLUSION: Eyes with choroidal melanoma had thicker choroids than unaffected fellow eyes. Increased choroidal thickness was more prominent in metabolically active tumors. Choroidal thickness significantly decreased in tumor eyes 6 months after treatment.

A competing risk analysis of cancer-specific mortality of initial treatment with radical prostatectomy versus radiation therapy in clinically localized high-risk prostate cancer.

BACKGROUND: There is no consensus on the optimal treatment for localized high-risk prostate cancer (PC), and much debate exists regarding the ideal treatment approach. For these reasons, we evaluated the competing risks of PC-specific mortality after initial therapy with radical prostatectomy (RP) versus radiotherapy (RT) in men with clinically localized high-risk PC. METHODS: We reviewed patients treated with RP and RT combined with androgen-deprivation therapy between 1990 and 2009. High-risk PC is defined as clinical stage ≥T3a, serum prostate-specific antigen (PSA) >20 ng/mL, or a biopsy Gleason sum of 8-10 according to National Comprehensive Cancer Network guidelines. Competing risk analysis was conducted to assess the association of RP (n = 251) or RT (n = 125) with cancer-specific mortality (CSM). Thereafter, secondary analysis with propensity score matching was conducted to further elucidate patient characteristics, with optimal matching of 0.25 times the standard deviation of propensity scores. RESULTS: With an overall median follow-up of 76 months, 35 (9.3 %) men with high-risk PC died due to PC (23 in the RT group and 12 in the RP group). The 5-year estimates of cancer-specific survival rate for men treated with RP and RT were 96.5 % (95 % confidence interval [CI] 94.2-98.9) and 88.3 % (95 % CI 82.8-94.3), respectively. Cumulative incidence estimates for CSM were statistically increased amongst men treated with RT (p = 0.002). Propensity score matching extracted 168 men with high-risk PC from the total patient cohort. Cumulative incidence estimates for CSM were statistically different amongst men treated with RT (p < 0.001). CONCLUSIONS: Initial treatment with RP versus RT was associated with a decreased risk of CSM in men with clinically localized high-risk PC.

Molecular markers predict distant metastases after adjuvant chemoradiation for rectal cancer.

PURPOSE: The outcomes of adjuvant chemoradiation for locally advanced rectal cancer are nonuniform among patients with matching prognostic factors. We explored the role of molecular markers for predicting the outcome of adjuvant chemoradiation for rectal cancer patients. METHODS AND MATERIALS: The study included 68 patients with stages II to III rectal adenocarcinoma who were treated with total mesorectal excision and adjuvant chemoradiation. Chemotherapy based on 5-fluorouracil and leucovorin was intravenously administered each month for 6-12 cycles. Radiation therapy consisted of 54 Gy delivered in 30 fractions. Immunostaining of surgical specimens for COX-2, EGFR, VEGF, thymidine synthase (TS), and Raf kinase inhibitor protein (RKIP) was performed. RESULTS: The median follow-up was 65 months. Eight locoregional (11.8%) and 13 distant (19.1%) recurrences occurred. Five-year locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates for all patients were 83.9%, 78.7%, 66.7%, and 73.8%, respectively. LRFFS was not correlated with TNM stage, surgical margin, or any of the molecular markers. VEGF overexpression was significantly correlated with decreased DMFS (P=.045), while RKIP-positive results were correlated with increased DMFS (P=.025). In multivariate analyses, positive findings for COX-2 (COX-2+) and VEGF (VEGF+) and negative findings for RKIP (RKIP-) were independent prognostic factors for DMFS, DFS, and OS (P=.035, .014, and .007 for DMFS; .021, .010, and <.0001 for DFS; and .004, .012, and .001 for OS). The combination of both COX-2+ and VEGF+ (COX-2+/VEGF+) showed a strong correlation with decreased DFS (P=.007), and the combinations of RKIP+/COX-2- and RKIP+/VEGF- showed strong correlations with improved DFS compared with the rest of the patients (P=.001 and <.0001, respectively). CONCLUSIONS: Molecular markers can be valuable in predicting treatment outcome of adjuvant chemoradiation for rectal cancer patients.

Concurrent chemoradiotherapy followed by adjuvant chemotherapy in uterine cervical cancer patients with high-risk factors.

OBJECTIVES: To determine whether concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy is better than CCRT alone in the management of FIGO stage bulky IB and IIB uterine cervical cancer. METHODS: Two hundred and five FIGO stage bulky IB and IIB patients with squamous cell carcinoma of the uterine cervix treated with CCRT were divided into 2 groups: (1) CCRT alone (n=103, Group A) and (2) CCRT plus adjuvant chemotherapy (n=102, Group B), and treatment outcomes were retrospectively compared between the two patient groups. RESULTS: Only 63% of patients received all three planned cycles of adjuvant chemotherapy, while 16% received only one cycle because of increased treatment-related morbidity or other causes. There were no treatment-related deaths. Although 37 patients experienced failures after completion of treatment, no significant differences were found in patterns of local and regional failures between the two groups. The incidence of distant metastasis, including para-aortic or supraclavicular lymph node metastases, was not reduced in patients of Group B (8% in Group A vs. 7% in Group B). Overall five-year actuarial survival rates for Group A and Group B patients were 85% vs. 80%, and five-year disease-free survival rates were 83% vs. 78%, respectively. CONCLUSIONS: Our data failed to show discernable therapeutic advantage of adjuvant chemotherapy with given after CCRT for the management of FIGO stage bulky IB and IIB uterine cervical cancer patients. A future clinical trial will be necessary to test the clinical efficacy of the adjuvant treatment using newly developed agents in uterine cervical cancer patients.

The role of postoperative external-beam radiotherapy in the management of patients with papillary thyroid cancer invading the trachea.

PURPOSE: To determine the role of adjuvant external-beam radiotherapy (EBRT) in the management of patients with well-differentiated thyroid cancer invading the trachea. METHODS AND MATERIALS: Of 1,098 thyroid cancer patients, 68 (6%) were found to have tracheal invasion, and they all received "shave" excision of the tracheal cartilage. Among them, 12 patients had no postoperative residuum, 43 patients had microscopic residuum, and 13 patients had macroscopic residuum. All patients were divided into two groups according to treatment modality with or without EBRT; (1) the control group (n = 43) and (2) the EBRT group (n = 25). RESULTS: The locoregional recurrence rate for EBRT patients was much lower than that of control patients (51% for the control group vs. 8% for the EBRT group) (p < 0.01). The 10-year local progression-free survival rate for the EBRT group was significantly better than that of the control group (89% in the EBRT group vs. 38% in the control group) (log-rank, p < 0.01). The use of adjuvant EBRT after conservative surgery was an independent prognostic factor in univariate and multivariate analyses. CONCLUSIONS: External-beam radiotherapy was found to be effective, particularly in patients with thyroid cancer invading the trachea with microscopic or gross residuum after conservative surgery.