Radiotherapy or Chemoradiation in Unresectable Biliary Cancer: A Retrospective Study.

BACKGROUND/AIM: To retrospectively evaluate the outcome of patients with unresectable biliary cholangiocarcinoma (CC) treated with radiotherapy (RT) plus/minus chemotherapy (CHT). MATERIALS AND METHODS: Data of patients with intrahepatic CC (ICC), Klatskin's tumor (KT), distal extrahepatic CC (ECC), and gallbladder cancer (GBC) diagnosed from 1991 to 2017 were retrospectively analyzed. The treatment was mainly based on RT plus concurrent CHT +/- brachytherapy (BRT) boost. The Kaplan-Meier method was used to calculate survival curves that were compared using the log-rank test. RESULTS: Seventy-six patients were included in this analysis (males: 59%; females: 41%; median age: 66.5 years). A minority of patients (7.9%) were treated for disease recurrence after surgery. According to TNM, 78.5% of patients had T stage >3 and 77.6% of patients were treated with concurrent CHT-RT while 22.3% received RT followed by sequential CHT. Median RT dose was 50 Gy (range: 16-75 Gy) delivered with conventional fractionation. CHT was based on Gemcitabine or 5-fluorouracil. BRT was prescribed to 51.3% of patient with a median dose of 14 Gy. Reported Grade ≥3 acute GI and hematological toxicity were 13.2% and 8.1%, respectively. No other severe acute toxicities were reported. One- and 2-year overall survival (OS) were 58.1% and 25.8%, respectively (median: 13.5 months), while 1- and 2-year progression-free survival (PFS) were 43.4% and 9.4%, respectively. None of the following variables had a significant impact on OS and PFS: BRT boost, tumor site, concurrent CHT, and the drugs used in concurrent CHT. In contrast, patients receiving RT with 2D technique showed a PFS significantly higher compared to patients treated with the 3D technique (median: 15.5 vs. 8.5 months; p=0.02). CONCLUSION: Combined modality treatment (RT+CHT±BRT) in unresectable biliary cancer was associated with acceptable toxicity and OS comparable to the actual standard treatment (CHT). The significantly improved PFS in patients undergoing 2D-RT raises doubts regarding the adequacy of target delineation in these neoplasms.

Stereotactic body radiation therapy in cholangiocarcinoma: a systematic review.

OBJECTIVE: Stereotactic body radiation therapy (SBRT) has been used in the treatment of cholangiocarcinoma (CC) but toxicity and clinical results of SBRT in CC are still limited and sparse. Therefore, the aim of this systematic review was to analyze the results of SBRT in the setting of advanced CC. METHODS: A systematic literature search was conducted on PubMed, Scopus, and Cochrane library using the PRISMA methodology. Studies including at least 10 patients with diagnosis of advanced CC regardless of tumor site and other treatments were included. The primary outcome was overall survival (OS) and secondary endpoints were local control (LC) and toxicity rates. The ROBINS-I risk of bias tool was used. RESULTS: 10 studies (231 patients) fulfilled the selection criteria and were included in this review. All but one study showed moderate to serious risk of bias. Median follow up was 15 months (range: 7.8-64.0 months). Pooled 1 year OS was 58.3% (95% CI: 50.2-66.1%) and pooled 2 year OS was 35.5% (95% CI: 22.1-50.1%). Pooled 1 year LC was 83.4%, (95% CI: 76.5-89.4%). The reported toxicities were acceptable and manageable with only one treatment-related death. CONCLUSION: The role of SBRT in CC is not yet supported by robust evidence in literature. However, within this limit, preliminary results seem almost comparable to the ones of standard chemotherapy or chemoradiation. ADVANCES IN KNOWLEDGE: SBRT seems effective in terms of LC with acceptable treatment-related toxicities. Therefore, SBRT can be considered a therapeutic option at least in selected patients with CC, possibly combined with adjuvant chemotherapy (CHT).

Postoperative Hypofractionated Radiation Therapy in Prostate Carcinoma: A Systematic Review.

BACKGROUND/AIM: A systematic review on toxicity, local control (LC), overall survival (OS), and biochemical relapse-free survival (bRFS) after postoperative hypofractionated radiotherapy (HFRT) on prostate cancer (PCa) was performed. MATERIALS AND METHODS: Based on the PRISMA methodology, studies reporting clinical results after adjuvant or salvage HFRT were included. RESULTS: A total of 1,208 patients from 17 eligible studies were included. Median follow-up was 30 months. No case of severe acute gastrointestinal (GI) toxicity was recorded. Grade ≥3 acute genitourinary (GU) toxicity ranged between 0% and 3%. Different rates of grade ≥2 late GI (range=0-8.7%) and GU (range=0-66%) toxicity were recorded. Encouraging results on LC, OS, and bRFS were reported. CONCLUSION: Acute toxicity does not seem to be increased in patients receiving postoperative HFRT, but the results of late-GU toxicity are conflicting. Further prospective studies are needed before including postoperative HFRT in clinical practice.

Clinical Target Volume in Biliary Carcinoma: A Systematic Review of Pathological Studies.

BACKGROUND/AIM: Radiotherapy is a treatment option for both adjuvant and neo-adjuvant settings for biliary tract cancer. Guidelines on the delineation of the target volume of lymph nodes are lacking; only generic indications are available, without specific recommendations for different primary tumour locations (e.g. intrahepatic, extrahepatic biliary tract or gallbladder cancer). The aim of this study was to systematically review available literature to provide recommendations on lymph node target volume delineation in patients with unresectable biliary tumour. MATERIALS AND METHODS: A systematic search of electronic databases was performed up to July 2016. The primary outcome measure was the rate of lymph node involvement according to the location of primary biliary tumour. Sites with ≥5% of nodal metastases were considered in the clinical target volume for radiotherapy planning. RESULTS: Twelve studies (1075 patients) were included. The most frequent site of lymph node metastasis in intrahepatic biliary tree carcinoma was retroportal (61.1%, 95% confidence interval (CI)=50.7-70-6%). Other frequently involved lymph nodes were along the hepatoduodenal ligament [frequency=38.7%, 95% CI=31.0-47.0%], those along the common hepatic artery (17.0%, 95% CI=8.2-31.9%) and the hilar nodes (16.9%, 95% CI=13.2-21.4%). In extrahepatic biliary tree cancer, the most frequently involved lymph nodes were the pericholedochal (42.7%, 95% CI=33.8-52.1%) and those along the hepatoduodenal ligament (40.3%, 95% CI=32.4-48.8%). Other commonly involved nodal regions included retroportal lymph nodes (30.9%, 95% CI=23.0-40.1%), pancreaticoduodenal anterior and posterior nodes (30.1%, 95% CI=12.2-57.1%), those along the common hepatic artery (19.7%, 95% CI=11.8-31.0%) and para_aortic nodes (15.2%, 95% CI=8.0-27.0%). The most common site of metastases in gallbladder cancer were the pericholedochal nodes (25.2%, 95% CI=18.6-33.2%), those along the cystic duct (23%, 95% CI=16.6-30.8%), and retroportal nodes (17.1%, 95% CI=11.6-24.5%). CONCLUSION: Biliary tract cancer has a high propensity for regional lymphatic metastases. An evidence-based nodal target definition of biliary tract cancer based on primary tumour location was proposed.

Individually optimized stereotactic radiotherapy for pancreatic head tumors: A planning feasibility study.

AIM: Aim of this study was to perform a planning feasibility analysis of a 3-level dose prescription using an IMRT-SIB technique. BACKGROUND: Radiation therapy of locally advanced pancreatic cancer should administer a minimum dose to the duodenum and a very high dose to the vascular infiltration areas to improve the possibility of a radical resection. MATERIALS AND METHODS: Fifteen patients with pancreatic head adenocarcinoma and vascular involvement were included. The duodenal PTV (PTVd) was defined as the GTV overlapping the duodenal PRV. Vascular CTV (CTVv) was defined as the surface of contact or infiltration between the tumor and vessel plus a 5 mm margin. Vascular PTV (PTVv) was considered as the CTVv plus an anisotropic margin. The tumor PTV (PTVt) was defined as the GTV plus a margin including the PTVv and excluding the PTVd. The following doses were prescribed: 30 Gy (6 Gy/fraction) to PTVd, 37.5 Gy (7.5 Gy/fraction) to PTVt, and 45 Gy (9 Gy/fraction) to PTVv, respectively. Treatment was planned with an IMRT technique. RESULTS: The primary end-point (PTVv Dmean > 90%) was achieved in all patients. PTVv D98% > 90% was achieved in 6 patients (40%). OARs constraints were achieved in all patients. CONCLUSIONS: Although the PTVv D95% > 95% objective was achieved only in 40% of patients, the study showed that in 100% of patients it was possible to administer a strongly differentiated mean/median dose. Prospective trials based on clinical application of this strategy seem to be justified in selected patients without overlap between PTVd and PTVv.

Automatic segmentation software in locally advanced rectal cancer: READY (REsearch program in Auto Delineation sYstem)-RECTAL 02: prospective study.

To validate autocontouring software (AS) in a clinical practice including a two steps delineation quality assurance (QA) procedure.The existing delineation agreement among experts for rectal cancer and the overlap and time criteria that have to be verified to allow the use of AS were defined.Median Dice Similarity Coefficient (MDSC), Mean slicewise Hausdorff Distances (MSHD) and Total-Time saving (TT) were analyzed.Two expert Radiation Oncologists reviewed CT-scans of 44 patients and agreed the reference-CTV: the first 14 consecutive cases were used to populate the software Atlas and 30 were used as Test.Each expert performed a manual (group A) and an automatic delineation (group B) of 15 Test patients.The delineations were compared with the reference contours.The overlap between the manual and automatic delineations with MDSC and MSHD and the TT were analyzed.Three acceptance criteria were set: MDSC ≥ 0.75, MSHD ≤1mm and TT sparing ≥ 50%.At least 2 criteria had to be met, one of which had to be TT saving, to validate the system.The MDSC was 0.75, MSHD 2.00 mm and the TT saving 55.5% between group A and group B. MDSC among experts was 0.84.Autosegmentation systems in rectal cancer partially met acceptability criteria with the present version.

Robotic radiosurgery in pancreatic cancer: A systematic review.

AIM: To present a systematic review of techniques and clinical results. METHODS: A systematic review of published literature was performed. Only studies reporting patient outcome after radiosurgery (single fraction) delivered with robotic devices [i.e., robotic radiosurgery (RRS)] have been analyzed. RESULTS: A total of 96 patients from 5 studies were included. The studies are characterized by small series and different methods in terms of dose, target definition, combination with chemotherapy and/or standard fractionated radiotherapy and evaluation modalities. Preliminary results are positive in terms of tumor response (ORR = 56%) and local control of the tumor (crude rate of local progressions: 19.5%). Results for median overall survival (11.4 mo) seem comparable with the ones of prolonged chemoradiation (range: 8.6-13.0 mo). However, gastrointestinal toxicity seems to be the main limitation of RRS, especially at the duodenal level. CONCLUSION: RRS allows for local treatment in a shortened time (1 fraction) compared to traditional treatments (about 1 mo), providing the possibility for an easy integration with systemic therapies. Preliminary results did not show any outcome differences compared to standard chemoradiation. Thus, further efforts to reduce gastrointestinal toxicity are strongly needed.

External beam radiotherapy plus 24-hour continuous infusion of gemcitabine in unresectable pancreatic carcinoma: long-term results of a phase II study.

PURPOSE: To evaluate the efficacy of gemcitabine-based chemoradiation (CT-RT) in treating patients (pts) affected by locally advanced pancreatic cancers (LAPC). METHODS AND MATERIALS: Weekly gemcitabine (100 mg/m(2)) was given as a 24-hour infusion during the course of three-dimensional radiotherapy (50.4 Gy to the tumor, 39.6 Gy to the nodes). After CT-RT, pts received five cycles of sequential chemotherapy with gemcitabine (1000 mg/m(2); 1, 8, q21). Response rate was assessed according to World Health Organization criteria 6 weeks after the end of CT-RT. Local control (LC), time to progression (TTP), metastases-free survival (MFS), and overall survival (OS) were analyzed by the Kaplan Meier method. RESULTS: Forty pts (male/female 22/18; median age 62 years, range, 36-76) were treated from 2000 to 2005. The majority had T4 tumour (n = 34, 85%), six pts (15%) had T3 tumour. Sixteen pts (40%) were node positive at diagnosis. Grade 3-4 acute toxicity was observed in 21 pts (52.5%). Thirty pts (75%) completed the treatment schedule. A clinical response was achieved in 12 pts (30%). With a median follow-up of 76 months (range, 32-98), 2-year LC was 39.6% (median, 12 months), 2-year TTP was 18.4% (median, 10 months), and 2-year MFS was 29.7% (median, 10 months). Two-year OS (25%; median, 15.5 months) compared with our previous study on 5-fluorouracil-based CT-RT (2.8%) was significantly improved (p <0.001). CONCLUSIONS: Gemcitabine CT-RT seems correlated with improved outcomes. Healthier patients who are likely to complete the treatment schedule may benefit most from this therapy.

Intraoperative radiation therapy in resected pancreatic carcinoma: long-term analysis.

PURPOSE: The combination of external radiotherapy (RT) plus intraoperative radiotherapy (IORT) in patients with pancreatic cancer is still debated. This study presents long-term results (minimum follow-up, 102 months) for 26 patients undergoing integrated adjuvant RT (external RT+IORT). METHODS AND MATERIALS: From 1990 to 1995, a total of 17 patients with pancreatic cancer underwent IORT (10 Gy) and postoperative external RT (50.4 Gy). Preoperative "flash" RT was included for the last 9 patients. The liver and pancreatic head received 5 Gy (two 2.5-Gy fractions) the day before surgery. In the subsequent period (1996-1998), 9 patients underwent preoperative concomitant chemoradiation (39.6 Gy) with 5-fluorouracil, IORT (10 Gy), and adjuvant chemotherapy. RESULTS: Preoperative chemoradiation was completed in all patients, whereas postoperative therapy was completed in 13 of 17 patients. All 26 patients underwent pancreatectomy (25 R0 and one R1 resections). One patient died of postoperative complications (3.8%) not related to IORT. The 9 patients undergoing concomitant chemoradiation were candidates for adjuvant chemotherapy; however, only 4 of 9 underwent adjuvant chemotherapy. At last follow-up, 4 patients (15.4%) were alive and disease free. Disease recurrence was documented in 20 patients (76.9%). Sixteen patients (61.5%) showed distant metastasis, and 5 patients (19.2%) showed local recurrence. The incidence of local recurrence in R0 patients was 4 of 25 (16.0%). The overall 5-year survival rate was 15.4%. There was significant correlation with overall survival of tumor diameter (p=0.019). CONCLUSIONS: The incidence of local recurrence in this long follow-up series (19.2%) was definitely less than that reported in other studies of adjuvant RT (approximately 50%), suggesting a positive impact on local control of integrated adjuvant RT (IORT+external RT).

Analysis of intraprostatic failures in patients treated with hormonal therapy and radiotherapy: implications for conformal therapy planning.

PURPOSE: Conformal therapy of prostate cancer is based on high-dose irradiation to the entire prostate gland. The aim of this study was to analyze the pattern of intraprostatic recurrence in patients undergoing external beam radiotherapy (EBRT) at a dose of 65-70 Gy to evaluate whether conventional radiotherapy doses are adequate to control microscopic disease outside the primary tumor and therefore whether high-dose irradiation can be exclusively focused on the macroscopic disease. METHODS AND MATERIALS: The clinical and radiologic reports of 118 patients with prostate cancer undergoing EBRT (64.8-70.2 Gy) combined with hormonal therapy were evaluated. In all patients, before and after therapy, the size and site of the primary neoplasm within the prostate were assessed by clinical examination and imaging studies. RESULTS: With a median follow-up of 45 months (range 14-119), the 5-year actuarial local control rate was 83.9%. Twelve patients had an intraprostatic recurrence, with the appearance of a new nodule (in 5 patients with a complete response after therapy) or increased nodular size compared with the minimal size (in the 7 other patients). In all patients, on the basis of a semiquantitative evaluation of the site of recurrence, this was shown to originate within the initial tumor volume. CONCLUSION: The results of this analysis seem to confirm some histologic findings observed in patients undergoing prostatectomy for local recurrence after radiotherapy that suggest that local recurrence usually originates in the primary tumor rather than in focal prostatic intraepithelial neoplasia. This observation might justify the application of conformal therapy procedures aimed at identifying the gross tumor volume, in the phase of boost, exclusively with the primary tumor.