Intraoperative Radiotherapy for Resectable Pancreatic Cancer Using a Low-Energy X-Ray Source:Postoperative Complications and Early Outcomes

Purpose@#We evaluated the safety, feasibility, and early treatment outcomes of intraoperative radiotherapy (IORT) using a lowenergy X-ray source. @*Materials and Methods@#Patients with resectable pancreatic cancer were enrolled in this single-institution, prospective, singlearm, phase II trial. Patients underwent surgery and IORT with 10 Gy prescribed at a 5-mm depth from the tumor bed using a 50 kV X-ray source (Intrabeam, Carl Zeiss). Six cycles of adjuvant gemcitabine-based chemotherapy were administered 8–12 weeks after surgery. @*Results@#A total of 41 patients were included. Thirty-one patients (75.6%) underwent wide R0 resection, while 5 (12.2%) underwent R1 resection and 5 (12.2%) underwent narrow R0 resection (retroperitoneal margin <1 mm). Grade 3 postoperative complications were reported in only one patient (4.9%) who needed additional surgery due to ulcer perforation. At a median follow-up of 9 months, four patients showed local-only recurrence, nine had distant metastases, and two showed both local and distant recurrence. The 1-year local control rate was 76.4%. @*Conclusion@#Our preliminary report suggests that IORT is well-tolerated and feasible in patients with resectable pancreatic cancer. Further follow-up is needed to confirm the clinical benefits of IORT in terms of local control and overall survival.Trial Registration: Clinical trial registration No. (NCT03273374).

Kallikrein 5 overexpression is associated with poor prognosis in uterine cervical cancer / 부인종양

Objective@#Kallikrein 5 (KLK5), which is frequently observed in normal cervico-vaginal fluid, is known to be related to prognosis in several solid tumors. We investigated the prognostic significance of KLK5 in uterine cervical cancer using tumor tissue microarray and immunohistochemistry staining. @*Methods@#We analyzed samples of 165 patients with uterine cervical cancer who received definitive radiation therapy between 2004 and 2012. We divided patients into two groups stratified by their KLK5 activity by immunohistochemistry staining: negative/weak (0–1+) (n=120 patients) and moderate/strong (2–3+) group (n=45 patients). Patient and tumor characteristics, patterns of failure, and survival outcomes were compared. Univariable and multivariable analyses were performed to identify prognostic factors. @*Results@#Patients with KLK5 2–3+ were younger (median: 52 vs. 60 years) and had frequent paraaortic lymph node involvement (40.0% vs. 18.3%) than those with KLK5 0–1+. With a median follow-up of 60.8 (interquartile range, 47.5–77.9) months, patients with KLK5 2–3+ had inferior 5-year locoregional recurrence-free survival and distant metastasis-free survival of 61.7% (vs. 77.5% in KLK5 0–1+ group) and 59.4% (vs. 72.8% in the KLK5 0–1+ group), respectively (all p<0.05). KLK5 2–3+ expression retained its significance after adjusting for other well-known prognostic factors of tumor size and stage in multivariable analysis. @*Conclusions@#KLK5 overexpression is associated with the aggressiveness of cervical cancer and may underlie the diminished response to conventional treatments. Therefore, KLK5 could be a reliable prognostic factor in cervical cancer.

Kallikrein 5 overexpression is associated with poor prognosis in uterine cervical cancer / 부인종양

Objective@#Kallikrein 5 (KLK5), which is frequently observed in normal cervico-vaginal fluid, is known to be related to prognosis in several solid tumors. We investigated the prognostic significance of KLK5 in uterine cervical cancer using tumor tissue microarray and immunohistochemistry staining. @*Methods@#We analyzed samples of 165 patients with uterine cervical cancer who received definitive radiation therapy between 2004 and 2012. We divided patients into two groups stratified by their KLK5 activity by immunohistochemistry staining: negative/weak (0–1+) (n=120 patients) and moderate/strong (2–3+) group (n=45 patients). Patient and tumor characteristics, patterns of failure, and survival outcomes were compared. Univariable and multivariable analyses were performed to identify prognostic factors. @*Results@#Patients with KLK5 2–3+ were younger (median: 52 vs. 60 years) and had frequent paraaortic lymph node involvement (40.0% vs. 18.3%) than those with KLK5 0–1+. With a median follow-up of 60.8 (interquartile range, 47.5–77.9) months, patients with KLK5 2–3+ had inferior 5-year locoregional recurrence-free survival and distant metastasis-free survival of 61.7% (vs. 77.5% in KLK5 0–1+ group) and 59.4% (vs. 72.8% in the KLK5 0–1+ group), respectively (all p<0.05). KLK5 2–3+ expression retained its significance after adjusting for other well-known prognostic factors of tumor size and stage in multivariable analysis. @*Conclusions@#KLK5 overexpression is associated with the aggressiveness of cervical cancer and may underlie the diminished response to conventional treatments. Therefore, KLK5 could be a reliable prognostic factor in cervical cancer.

Radiotherapy for initial clinically positive internal mammary nodes in breast cancer

PURPOSE: Internal mammary lymph node (IMN) involvement is associated with poor prognosis in breast cancer. This study investigated the treatment outcomes of initial clinically IMN-positive breast cancer patients who received adjuvant radiotherapy (RT), including IMN irradiation, following primary breast surgery. MATERIALS AND METHODS: We retrospectively reviewed data of 95 breast cancer patients with clinically detected IMNs at diagnosis treated with surgery and RT between June 2009 and December 2015. Patients received adjuvant RT to the whole breast/chest wall and regional lymph node (axillary, internal mammary, and supraclavicular) areas. Twelve patients received an additional boost to the IMN area. RESULTS: The median follow-up was 43.2 months (range, 4.5 to 100.5 months). Among 77 patients who received neoadjuvant chemotherapy, 52 (67.5%) showed IMN normalization and 19 (24.6%) showed a partial response to IMN. There were 3 and 24 cases of IMN failure and any recurrence, respectively. The 5-year IMN failure-free survival, disease-free survival (DFS), and overall survival (OS) were 96%, 70%, and 84%, respectively. IMN failure-free survival was significantly affected by resection margin status (97.7% if negative, 87.5% for close or positive margins; p = 0.009). All three patients with IMN failure had initial IMN size ≥1 cm and did not receive IMN boost irradiation. The median age of the three patients was 31 years, and all had hormone receptor-negative tumors. CONCLUSION: RT provides excellent IMN control without the support of IMN surgery. Intensity-modulated radiotherapy, including IMN boost for breast cancer patients, is a safe and effective technique for regional lymph node irradiation.

Survival and Functional Outcome after Treatment for Primary Base of Tongue Cancer: A Comparison of Definitive Chemoradiotherapy versus Surgery Followed by Adjuvant Radiotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to compare the clinical and functional outcomes in patients with primary base of tongue (BOT) cancer who received definitive radiotherapy (RT) or surgery followed by radiotherapy (SRT). MATERIALS AND METHODS: Between January 2002 and December 2016, 102 patients with stage I-IVB primary BOT cancer underwent either definitive RT (n=46) or SRT (n=56), and treatment outcomes were compared between two groups. The expression of p16 was also analyzed. RESULTS: The RT group had more patients with advanced T stage (T3-4) disease (58.7% vs. 35.7%, p=0.021) and who received chemotherapy (91.3% vs. 37.5%, p < 0.001) than the SRT group. At a median follow up of 36.9 months (range, 3.3 to 181.5 months), the 5-year overall survival (OS) and disease-free survival (DFS) were 75.5% and 68.7%, respectively. With respect to treatment group, the 5-year OS and DFS in the RT and SRT groups did not differ significantly (OS, 68.7% vs. 80.5%, p=0.601; DFS, 63.1% vs. 73.1%, p=0.653). In multivariate analysis, OS differed significantly according to p16 expression (p16-negative vs. p16-positive; hazard ratio [HR], 0.145; 95% confidence interval [CI], 0.025 to 0.853; p=0.033). Regarding DFS, p16 expression (p16-negative vs. p16-positive; HR, 0.164; 95% CI, 0.045 to 0.598; p=0.006) showed a significant effect in multivariate analysis. Functional defects (late grade ≥ 3 dysphagia or voice alteration) were more frequently reported in the SRT than in the RT group (16.1% vs. 2.2%, p=0.021). CONCLUSION: Despite advanced disease, patients in the RT group showed comparable survival outcomes and better functional preservation than those in the SRT group.

Kilovoltage radiotherapy for companion animals: dosimetric comparison of 300 kV, 450 kV, and 6 MV X-ray beams

Radiotherapy for the treatment of cancer in companion animals is currently administered by using megavoltage X-ray machines. Because these machines are expensive, most animal hospitals do not perform radiotherapy. This study evaluated the ability of relatively inexpensive kilovoltage X-ray machines to treat companion animals. A simulation study based on a commercial treatment-planning system was performed for tumors of the brain (non-infectious meningoencephalitis), nasal cavity (malignant nasal tumors), forefoot (malignant muscular tumors), and abdomen (malignant intestinal tumors). The results of kilovoltage (300 kV and 450 kV) and megavoltage (6 MV) X-ray beams were compared. Whereas the 300 kV and 6 MV X-ray beams provided optimal radiation dose homogeneity and conformity, respectively, for brain tumors, the 6 MV X-rays provided optimal homogeneity and radiation conformity for nasal cavity, forefoot, and abdominal tumors. Although megavoltage X-ray beams provided better radiation dose distribution in most treated animals, the differences between megavoltage and kilovoltage X-ray beams were relatively small. The similar therapeutic effects of the kilovoltage and 6 MV X-ray beams suggest that kilovoltage X-ray beams may be effective alternatives to megavoltage X-ray beams in treating cancers in companion animals.

Predictive factors of symptomatic radiation pneumonitis in primary and metastatic lung tumors treated with stereotactic ablative body radiotherapy

PURPOSE: Although stereotactic ablative body radiotherapy (SABR) is widely used therapeutic technique, predictive factors of radiation pneumonitis (RP) after SABR remain undefined. We aimed to investigate the predictive factors affecting RP in patients with primary or metastatic lung tumors who received SABR. MATERIALS AND METHODS: From 2012 to 2015, we reviewed 59 patients with 72 primary or metastatic lung tumors treated with SABR, and performed analyses of clinical and dosimetric variables related to symptomatic RP. SABR was delivered as 45–60 Gy in 3–4 fractions, which were over 100 Gy in BED when the α/β value was assumed to be 10. Tumor volume and other various dose volume factors were analyzed using median value as a cutoff value. RP was graded per the Common Terminology Criteria for Adverse Events v4.03. RESULTS: At the median follow-up period of 11 months, symptomatic RP was observed in 13 lesions (12 patients, 18.1%), including grade 2 RP in 11 lesions and grade 3 in 2 lesions. Patients with planning target volume (PTV) of ≤14.35 mL had significantly lower rates of symptomatic RP when compared to others (8.6% vs. 27%; p = 0.048). Rates of symptomatic RP in patients with internal gross tumor volume (iGTV) >4.21 mL were higher than with ≤4.21 mL (29.7% vs. 6.1%; p = 0.017). CONCLUSIONS: The incidence of symptomatic RP following treatment with SABR was acceptable with grade 2 RP being observed in most patients. iGTV over 4.21 mL and PTV of over 14.35 mL were significant predictive factors related to symptomatic RP.

Treatment outcome of radiation therapy and concurrent targeted molecular therapy in spinal metastasis from renal cell carcinoma

PURPOSE: To evaluate the clinical outcomes of patients who underwent radiation therapy with or without targeted molecular therapy for the treatment of spinal metastasis from renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 28 spinal metastatic lesions from RCC patients treated with radiotherapy between June 2009 and June 2015 were retrospectively reviewed. Thirteen lesions were treated concurrently with targeted molecular therapy (concurrent group) and 15 lesions were not (nonconcurrent group). Local control was defined as lack of radiographically evident local progression and neurological deterioration. RESULTS: At a median follow-up of 11 months (range, 2 to 58 months), the 1-year local progression-free rate (LPFR) was 67.0%. The patients with concurrent targeted molecular therapy showed significantly higher LPFR than those without (p = 0.019). After multivariate analysis, use of concurrent targeted molecular therapy showed a tendency towards improved LPFR (hazard ratio, 0.13; 95% confidence interval, 0.01 to 1.16). There was no difference in the incidence of systemic progression between concurrent and nonconcurrent groups. No grade ≥2 toxicities were observed during or after radiotherapy. CONCLUSION: Our study suggests the possibility that concurrent use of targeted molecular therapy during radiotherapy may improve LPFR. Further study with a large population is required to confirm these results.

Morphologic change of rectosigmoid colon using belly board and distended bladder protocol

PURPOSE: This study investigates morphologic change of the rectosigmoid colon using a belly board in prone position and distended bladder in patients with rectal cancer. We evaluate the possibility of excluding the proximal margin of anastomosis from the radiation field by straightening the rectosigmoid colon. MATERIALS AND METHODS: Nineteen patients who received preoperative radiotherapy between 2006 and 2009 underwent simulation in a prone position (group A). These patients were compared to 19 patients treated using a belly board in prone position and a distended bladder protocol (group B). Rectosigmoid colon in the pelvic cavity was delineated on planning computed tomography (CT) images. A total dose of 45 Gy was planned for the whole pelvic field with superior margin of the sacral promontory. The volume and redundancy of rectosigmoid colon was assessed. RESULTS: Patients in group B had straighter rectosigmoid colons than those in group A (no redundancy; group A vs. group B, 10% vs. 42%; p = 0.03). The volume of rectosigmoid colon in the radiation field was significantly larger in group A (56.7 vs. 49.1 mL; p = 0.009). In dose volume histogram analysis, the mean irradiated volume was lower in patients in group B (V45 27.2 vs. 18.2 mL; p = 0.004). In Pearson correlation coefficient analysis, the in-field volume of rectosigmoid colon was significantly correlated with the bladder volume (R = 0.86, p = 0.003). CONCLUSION: Use of a belly board and distended bladder protocol could contribute to exclusion of the proximal margin of anastomosis from the radiation field.

Morphologic change of rectosigmoid colon using belly board and distended bladder protocol

PURPOSE: This study investigates morphologic change of the rectosigmoid colon using a belly board in prone position and distended bladder in patients with rectal cancer. We evaluate the possibility of excluding the proximal margin of anastomosis from the radiation field by straightening the rectosigmoid colon. MATERIALS AND METHODS: Nineteen patients who received preoperative radiotherapy between 2006 and 2009 underwent simulation in a prone position (group A). These patients were compared to 19 patients treated using a belly board in prone position and a distended bladder protocol (group B). Rectosigmoid colon in the pelvic cavity was delineated on planning computed tomography (CT) images. A total dose of 45 Gy was planned for the whole pelvic field with superior margin of the sacral promontory. The volume and redundancy of rectosigmoid colon was assessed. RESULTS: Patients in group B had straighter rectosigmoid colons than those in group A (no redundancy; group A vs. group B, 10% vs. 42%; p = 0.03). The volume of rectosigmoid colon in the radiation field was significantly larger in group A (56.7 vs. 49.1 mL; p = 0.009). In dose volume histogram analysis, the mean irradiated volume was lower in patients in group B (V45 27.2 vs. 18.2 mL; p = 0.004). In Pearson correlation coefficient analysis, the in-field volume of rectosigmoid colon was significantly correlated with the bladder volume (R = 0.86, p = 0.003). CONCLUSION: Use of a belly board and distended bladder protocol could contribute to exclusion of the proximal margin of anastomosis from the radiation field.

Bladder filling variations during concurrent chemotherapy and pelvic radiotherapy in rectal cancer patients: early experience of bladder volume assessment using ultrasound scanner

PURPOSE: To describe the early experience of analyzing variations and time trends in bladder volume of the rectal cancer patients who received bladder ultrasound scan. MATERIALS AND METHODS: We identified 20 consecutive rectal cancer patients who received whole pelvic radiotherapy (RT) and bladder ultrasound scan between February and April 2012. Before simulation and during the entire course of treatment, patients were scanned with portable automated ultrasonic bladder scanner, 5 times consecutively, and the median value was reported. Then a radiation oncologist contoured the bladder inner wall shown on simulation computed tomography (CT) and calculated its volume. RESULTS: Before simulation, the median bladder volume measured using simulation CT and bladder ultrasound scan was 427 mL (range, 74 to 1,172 mL) and 417 mL (range, 147 to 1,245 mL), respectively. There was strong linear correlation (R = 0.93, p < 0.001) between the two results. During the course of treatment, there were wide variations in the bladder volume and every time, measurements were below the baseline with statistical significance (12/16). At 6 weeks after RT, the median volume was reduced by 59.3% to 175 mL. Compared to the baseline, bladder volume was reduced by 38% or 161 mL on average every week for 6 weeks. CONCLUSION: To our knowledge, this study is the first to prove that there are bladder volume variations and a reduction in bladder volume in rectal cancer patients. Moreover, our results will serve as the basis for implementation of bladder training to patients receiving RT with full bladder.