Impact of radiation dose on complications among women with breast cancer who underwent breast reconstruction and post-mastectomy radiotherapy: A multi-institutional validation study.

PURPOSE: Emerging data suggest that higher radiation doses in post-mastectomy radiotherapy may be associated with an increased risk of reconstruction complications. This study aimed to validate previous findings regarding the impact of radiation dose on complications among women with breast cancer using a multi-center dataset. METHODS: Fifteen institutions participated, and women with breast cancer who received radiotherapy after either autologous or prosthetic breast reconstruction were included. The primary endpoint was major post-radiation therapy complications requiring re-operation for explantation, flap failure, or bleeding control. RESULTS: In total, 314 patients were included. Radiotherapy was performed using both conventional fractionation and hypofractionation in various schedules. The range of the radiation therapy dose in Equivalent Dose in 2 Gy fractions (EQD2; α/ß = 3.5) varied from 43.4 to 71.0 Gy (median dose: 48.6 Gy). Boost radiation therapy was administered to 49 patients. Major post-radiation therapy complications were observed in 24 (7.6%) patients. In multivariate analysis, an increasing EQD2 per Gy (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.26-1.98; p < 0.001), current smoking status (OR: 25.48, 95% CI: 1.56-415.65; p = 0.023), and prosthetic breast reconstruction (OR: 9.28, 95% CI: 1.84-46.70; p = 0.007) were independently associated with an increased risk of major complications. CONCLUSION: A dose-response relationship between radiation dose and the risk of complications was validated in this multi-center dataset. In this context, we hypothesize that the use of hypofractionated radiotherapy (40 Gy in 15 fractions) may improve breast reconstruction outcomes. Our multi-center prospective observational study (NCT03523078) is underway to further validate this hypothesis.

Post-mastectomy radiation therapy in breast reconstruction: a patterns of care study of the Korean Radiation Oncology Group.

PURPOSE: The details of breast reconstruction and radiation therapy (RT) vary between institutions; therefore, we sought to investigate the practice patterns of radiation oncologists who specialize in breast cancer. MATERIALS AND METHODS: We identified the practice patterns and inter-hospital variations from a multi-center cohort of women with breast cancer who underwent post-mastectomy RT (PMRT) to the reconstructed breast at 16 institutions between 2015 and 2016. The institutions were requested to contour the target volume and produce RT plans for one representative case with five different clinical scenarios and answer questionnaires which elicited infrastructural information. We assessed the inter-institutional variations in RT in terms of the target, normal organ delineation, and dose-volume histograms. RESULTS: Three hundred fourteen patients were included; 99% of them underwent immediate reconstruction. The most irradiated material was tissue expander (36.9%) followed by transverse rectus abdominis musculocutaneous flap (23.9%) and silicone implant (12.1%). In prosthetic-based reconstruction with tissue expander, most patients received PMRT following partial deflation. Conventional fractionation and hypofractionation RT were used in 66.6% and 33.4% patients, respectively (commonest: 40.05 Gy in 15 fractions [17.5%]). Furthermore, 15.6% of the patients received boost RT and 53.5% were treated with bolus. Overall, 15 physicians responded to the questionnaires and six submitted their contours and RT plans. There was a significant variability in target delineations and RT plans between physicians, and between clinical scenarios. CONCLUSION: Adjuvant RT following post-mastectomy reconstruction has become a common practice in Korea. The details vary significantly between institutions, which highlights an urgent need for standard protocol in this clinical setting.

Gene promoter hypermethylation in tumors and plasma of breast cancer patients.

PURPOSE: To measure the hypermethylation of four genes in primary tumors and paired plasma samples to determine the feasibility of gene promoter hypermethylation markers for detecting breast cancer in the plasma. MATERIALS AND METHODS: DNA was extracted from the tumor tissues and peripheral blood plasma of 34 patients with invasive breast cancer, and the samples examined for aberrant hypermethylation in cyclin D2, retinoic acid receptor beta (RARbeta), twist and high in normal-1 (HIN-1) genes using methylation-specific PCR (MSP), and the results correlated with the clinicopathological parameters. RESULTS: Promoter hypermethylation was detected at high frequency in the primary tumors for cyclin D2 (53%), RARbeta (56%), twist (41%) and HIN-1 (77%). Thirty-three of the 34 (97%) primary tumors displayed promoter hypermethylation in at least one of the genes examined. The corresponding plasma samples showed hypermethylation of the same genes, although at lower frequencies (6% for cyclin D2, 16% for RARbeta, 36% for twist, and 54% for HIN-1). Overall, 22 of the 33 (67%) primary tumors with hypermethylation of at least one of the four genes also had abnormally hypermethylated DNA in their matched plasma samples. No significant relationship was recognized between any of the clinical or pathological parameters (tumor size, axillary lymph node metastasis, stage, or Ki-67 labeling index) with the frequency of hypermethylated DNA in the primary tumor or plasma. CONCLUSION: The detection of aberrant promoter hypermethylation of cancer-related genes in the plasma may be a useful tool for the detection of breast cancer.

Extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue-type of the orbit and ocular adnexa.

Non-Hodgkin's lymphomas of the orbit and ocular adnexa (OOA), the majority of which are extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue-type (MALT lymphomas), are a rare disorder. The aim of this study was to evaluate the clinical features and treatment outcomes and complications in patients with MALT lymphoma of OOA. Thirty-seven patients with a histologically verified diagnosis of MALT lymphoma of OOA were included in this retrospective, observational case study. There were 22 (59%) men and 15 (41%) women, with a median age of 44 years (range, 21-80 years). The most common presenting complaint was a slowly growing orbital mass. The stages were IA(E) in 74%, IA(EE) (bilateral involvement) in 18%, IIIA(E) in 6%, and IVA(E) in 3%. None of the patients had an elevated value of LHD or beta(2)-microglobulin. Surgical resection alone was attempted as the sole treatment in two patients, but tumor recurred 19 and 24 months after surgery. Radiotherapy, with a median tumor dose of 3,060 cGy, was administered in 29 patients; all of the patients achieved complete remission, and none of them had severe later complications. Combination chemotherapy alone was employed in three patients with stage IIIA(E) or IVA(E). With a median follow-up duration of 21 months, the 3-year overall survival (OS) rate and event-free survival (EFS) rate were 97% and 86%, respectively. Subgroup analysis of the patients with localized disease, who received radiotherapy as an initial treatment modality, revealed that 3-year OS rate and EFS rate were 100% and 93%, respectively. All disease recurrences were documented histologically as MALT lymphoma. In conclusion complete staging evaluation is needed to select an adequate treatment modality. Radiotherapy alone can produce excellent local control and survival in patients with localized MALT lymphoma of OOA. Systemic chemotherapy should be considered in patients with advanced stages or systemic manifestation.

Pain and its treatment in patients with cancer in Korea.

Substantial pain is experienced by a lot of patients with cancer, and undertreated pain significantly undermines their quality of life. Despite international and national guidelines on cancer pain management, the practical effectiveness of management is still problematic. We did a prospective cross-sectional survey on pain prevalence, pain intensity, its impact on daily activity, and adequacy of pain management in 823 patients treated by medical oncologists and radiologic oncologists. At the time of the survey, 29.7% of the patients had pain that was moderate or severe. Performance status and tumor extent were significant predictors of pain presence and its intensity. Pain severity and the proportion of the patients whose function is impaired are highly associated. Among the patients with pain, only 37% rated pain relief as satisfactory. Forty-one percent of the patients with pain received inadequate pain management. Physicians did not adjust the analgesic prescription in about 53% of the patients who reported severe pain. These results demonstrate the alarming degree of undertreatment of pain in patients with cancer in Korea, and indicate the need to improve the management of cancer-related pain. Future research should elucidate the factors that impede adequate pain management in order to overcome obstacles to adequate treatment.

Diffusion-weighted MR imaging of metastatic disease of the spine: assessment of response to therapy.

BACKGROUND AND PURPOSE: In cases of metastatic disease of the spine, monitoring the response to medical therapy with plain radiography, bone scanning, and conventional spin-echo sequence MR imaging is unsatisfactory because of the insensitivity or nonspecific findings of these imaging modalities. The purpose of this study was to investigate signal intensity changes of bone marrow after therapy by using diffusion-weighted MR imaging to monitor the response to medical therapy in cases of metastatic disease of the spine. METHODS: Twenty-four patients with metastatic disease of the spine were examined with MR imaging. Diffusion-weighted MR imaging and spin-echo MR imaging were performed in all patients before and after radiation therapy. Follow-up diffusion-weighted MR imaging and spin-echo MR imaging were performed for comparison purposes in nine cases at 1 month, in seven cases at 2 months, in seven cases at 3 months, and in three cases at 6 months after therapy. The diffusion-weighted MR imaging sequences were based on a steady-state free precession with a low b value (165 s/mm(2)) and a single shot stimulated echo-acquisition mode with a high b value (650 s/mm(2)). Apparent diffusion coefficient maps were obtained using two different b values incorporated in a diffusion-weighted single shot stimulated echo-acquisition mode sequence. Apparent diffusion coefficient maps were obtained in three cases. Signal intensity changes of the metastatic disease of the vertebral bone marrow before and after therapy on conventional spin-echo sequence and diffusion-weighted MR images were evaluated. RESULTS: As shown by diffusion-weighted MR imaging, metastatic disease of the vertebral bone marrow included in our study before therapy was hyperintense to normal vertebral bodies. In 23 patients with clinical improvement, metastatic disease of the spine after therapy was hypointense relative to normal vertebral bodies on the follow-up diffusion-weighted MR images. In one patient with hepatocellular carcinoma, the clinical symptoms did not improve and follow-up bone scanning performed 6 months after therapy showed increased uptake. Persistent hyperintense bone marrow after therapy was also noted on diffusion-weighted MR images. Decreased signal intensity of the metastatic disease of the spine on diffusion-weighted MR images was observed >1 month after therapy. CONCLUSION: Diffusion-weighted MR imaging shows that, with successful therapy, there is decreased signal intensity of metastatic disease of the vertebral bone marrow.